Diagnosis of IEM. And Emergency Management

Size: px
Start display at page:

Download "Diagnosis of IEM. And Emergency Management"

Transcription

1 Diagnosis of IEM And Emergency Management Susan Sklower Brooks, M.D., F.A.C.M.G. Professor of Pediatrics Professor of Obstetrics, Gynecology and Reproductive Sciences Robert Wood Johnson Medical School

2 What do they have in common? A full term 4 day old? A 2 year old from Pakistan? An 8 year old at summer camp? An 18 year old college student?

3 What Do They Have In Common? 1. An infectious disease? 2. A congenital heart disease? 3. An inborn error of metabolism? 4. Who cares? 100% 0% 0% 0% An infectious disease? A congenital heart di... An inborn error of me... Who cares?

4 The 2 year old child became unresponsive Case Report while traveling with her parents on the New Jersey Turnpike.

5 Summer Camp Escapade The 8 year old went to sleep-away camp for the first time. After several days she became increasing lethargic and was brought to a local ED. On arrival she was barely arousable.

6 College Binge? The 18 year old college student was brought to the ED unresponsive. She had been at a prefinal party with friends where alcohol was served.

7 What is the likely diagnosis? 1. Inborn Error of Metabolism? 2. Still not sure? 3. Who cares? 94% 6% 0% Inborn Error of Meta... Still not sure? Who cares?

8 Inborn Errors of Metabolism Amino acid disorders Organic acidemias Urea cycle disorders Carbohydrate metabolism disorders Mitochondrial disorders Mitochondrial fatty acid oxidation disorders Peroxisomal disorders Lysosomal storage disorders Purine and pyrimidine disorders Porphyrias Metal metabolism disorders

9 Major Presentation Categories for Inborn Errors of Metabolism Intoxication Energy Metabolism Complex Molecules Saudubray, JM et al, Semin Neonatol 2002: 7:3-15

10 Intoxication Symptom free interval- vomiting, lethargy coma, liver failure, etc Often treatable with diet or cofactor Small molecule disease amino acids, organic acids, fatty acid

11 Disorders of Energy Metabolism Hypoglycemia, failure to thrive, lactic acidemia, hypotonia, myopathy, SIDS Mitochondrial Disorders

12 Complex Molecules Permanent and progressive symptoms Lysosomal, peroxisomal For Some Enzyme Replacement Therapies

13 Amino/Organic Acid Disorders Disorders of Intermediary Metabolism Failure in breakdown pathways of amino acids Amino acid Amine (NH2) = Organic Acid Examples of Amino acid disorders PKU, Homocystinemia, Tyrosinemia Examples of Organic acid disorders Methylmalonic acidemia, propionic acidemia

14 Amino Disorder Presentation Generally non-acute Various symptoms dependent on disorder Homocystinuria thrombosis Tyrosinemia liver disease PKU hypopigmentation, seizures, intellectual disability

15 Organic Acidemias Organic acids = Amino Acids with the Amine group (NH2) removed PRESENTATION: Neonatal to Adult onset Neonatal presentation: Uncomplicated pregnancy Hypo or hypertonia Feeding problems Seizures Lethargy Unusual odors Metabolic encephalopathy Cerebral edema, coma, Multi-organ failure and death Lab Findings Hypoglycemia Metabolic acidosis Hyperammonemia Ketosis

16 Urea Cycle Disorders Primary functions of Urea cycle: elimination of waste nitrogen as urea to avoid accumulation of toxic nitrogen compounds synthesis of arginine

17 Urea Cycle Disorders Neonatal Onset Lethargy by 48-72hrs Vomiting Hypothermia Tachypnea and apnea Seizures Cerebral edema Metabolic alkalosis Death

18 Urea Cycle Disorders - Late Onset 1 yr through adulthood Hyperammonemic episodes confusion coma Associated with change in diet, illness (infection), surgery

19 Fatty Acid Oxidation Disorders Fatty acid transport and mitochondrial oxidation plays major role in energy production times of fasting and metabolic stress

20 Presentation of FAOD Cardiomyopathy Myopathy Encephalopathy Sudden death Hypoketotic hypoglycemia Elevated transaminases Elevated uric acid Elevated CK

21 Full Term 4 Day Old A 4-day-old male is brought to an ER by his parents because of poor feeding Mother reports decreased feeding beginning on DOL # 3 2 episodes of vomiting on DOL # 3 On DOL # 4, pt was less active, and went 6 hours without feeding or voiding

22 Birth History Mother GBS+, all other labs negative Mother adequately treated with 2 doses of antibiotics ROM = 12 hours, no maternal fever NSVD at 37 weeks gestation BW = 2.3 kg Discharged from nursery on DOL # 2 Newborn screen sent on DOL # 2 Formula feeding Q3 hours upon discharge

23 Physical Exam Weight 2.0 kg (down 14% from BW) Length and HC: 50 th percentile Temp=92 o, BP=56/28, HR=120, RR=36 Hypoactive infant with poor interaction AF sunken and dry mucous membranes Normal facies

24 Clinical Course Patient became less responsive and developed worsening respiratory distress Progressed to cardio-pulmonary arrest Resuscitated, and maintained on mechanical ventilation and vasoactive medications Developed seizure activity and was maintained on anticonvulsants

25 What are you thinking? 1. Sepsis 2. Cardiac 91% 3. Metabolic 4. Inexperienced parent 9% 0% 0% Sepsis Cardiac Metabolic Inexperienced parent

26 What laboratory studies should you order? 1. Blood Gas 2. CBC 3. Ammonia 4. Electrolytes 5. LFTs 6. UA 7. Lactic acid 8. All of the above Blood Gas 0% 0% 0% CBC Ammonia Electrolytes 0% LFTs 0% 0% UA Lactic acid 0% All of the above 100%

27 (Ca 2+ ) < (Gluc) ph 7.13 pco 2 11 HCO 3 <5 po Lactate 0.8 Ammonia = >1190 UA: 5.5 / / 2+ Ketones and Protein TP 5.6 AP 108 Alb 3.1 AST 50 TB 12.4 ALT 36

28 What do we know Neonate in coma Hypoglycemia Severe metabolic acidosis Hyperammonemia Ketonuria

29 Algorithm for the Diagnosis of the Neonate in Coma Modified from Hoffmann et al, Inherited Metabolic Diseases, 2002 Blood: NH 3, ph, Electrolytes, Urine: Ketones NH 3 No Acidosis NH 3 +/- Acidosis + Ketones ++ Anion gap NH 3 normal No Acidosis Urea cycle defect HHH syndrome Transient hyperammonemia of the newborn Amino Acids Organic acidemia (propionic, isovaleric, etc Organic Acids Amino acidemia Organic acidemia Organic Acids Amino Acids

30 Treatment Airway Correct dehydration and acidosis Prevent catabolism by providing calories (glucose at least 6 mg/kg/min; insulin if needed; intralipids) Stop potential toxins (Protein) Remove toxins (dialysis, activation of alternative pathways) Therapeutic cocktail (B12, folate, biotin, carnitine) Obtain urine and plasma for diagnostic tests Check newborn screen results Ogier de Baulny, H. Semin Neonatol 2002:7:17-26

31 Fatty acid oxidation d... Amino acidemia Organic acidemia Mitochondrial Urea cycle defect Diagnosis? 1. Fatty acid oxidation disorder 2. Amino acidemia 3. Organic acidemia 4. Mitochondrial 5. Urea cycle defect 83% 4% 8% 4% 0%

32 Further Studies Help Make the Specific Diagnosis NBS contacted increased C3 on screen C3 elevation MMA, PA, Multiple CoA Carboxylase Def Acylcarnitine profile confirmed elevated C3- carnitine Urine studies showed high levels of the following organic acids in his urine: Methylcitrate which is formed from conjugation of propionyl-coa with oxaloacetate Propionylglycine, which results from conjugation of propionyl-coa with glycine Tiglylglycine, which results from incomplete isoleucine catabolism

33 Diagnosis: NBS reported elevated C3 Differential: Propionic vs Methylmalonic acidemia FINAL DIAGNOSIS: Propionic Acidemia Long term treatment: restrict propiogenic amines (methionine, valine, isoleucine,threonine) by special diet; antibiotics to decrease gut bacteria

34 Case Report A 2 year old child became unresponsive while traveling with her parents on the New Jersey Turnpike.

35 Initial treatment EMS was called and took the child to the nearest emergency room where she was in coma and found to have ph of 6.9. She was given IV hydration and bicarbonate and transferred to the BMSCH

36 History Mother and children flew into JFK on day of admission from Pakistan (18 hr flight). On the flight baby was given milk and juice. On arrival she was noted to be lethargic but family thought it was from the long travel.

37 Additional History Past Medical History: Born in Pakistan Hospitalizations: DOL 8 - persistent vomiting 5 months - acidosis, apnea, bradycardia. Intubated and treated with electrolyte solutions. When discharged parents told to give her ½ strength Good Start formula, no meat, no eggs or dairy. Development: walking and talking Family Hx: Parents 1st cousins

38 Exam Patient sedated and intubated Normal facies No liver or spleen enlargement No skin lesions

39 Initial labs on Arrival ph 6.997pCO2 5.0 po2 59 HCO3 1.2 Na 146 Cl 112 HCO3 10 CA 8.9 K 4.5 BUN 17 Glu 227 Urine Ketones 2+ NH4 37 AST 32 ALT 17 Lactate 1.9 Anion Gap = Na+ - (Cl-+HCO3) Normal =10 +/ (112+10) = 24

40 What do we know Acute episodic decompensation Prolonged air flight poor feeding, dehydration, high protein, lactose+ feed Parental consanguinity Severe metabolic acidosis Raised anion gap, ketone + Normal ammonia, lactate, LFT, glucose

41 Treatment Airway Correct dehydration and acidosis always D10 or higher Prevent catabolism by providing calories Stop potential toxins (Protein) Remove toxins (consider dialysis, activation of alternative pathways) Therapeutic cocktail (B12, folate, biotin, carnitine) Obtain urine and plasma for diagnostic tests

42 Prolonged Hospital Course Respiratory support - intubation Hypotension requiring vasopressin Seizure-like activity CT scan large basal ganglia hypodensities, mildly enlarged ventricles

43 Diagnosis Amino acids essentially normal Organic Acids urine MMA very high DX: METHYLMALONIC ACIDURIA Later testing showed: CblA B12 responsive mutation 433C>T (R145X) homozygote a common mutation in the MMA gene

44 Propionic and Methylmalonic Acidemia Thymine uracil valine isoleucine methionine threonine cholesterol odd chain fatty acids ADENOSYL BIOTIN COBALAMIN (B12) Propionyl-CoA D-CH 3 malonyl-coa L-CH 3 malonyl-coa Succinyl CoA Propionyl CoA Carboxylase Methylmalonyl CoA racemase Methylmalonyl CoA mutase PROPIONIC ACID METHYLMALONIC ACID

45 Methylmalonic Acidemia B12 Responsive Cobalamin Defects Cbl A, B, H - faulty cobalamin synthesis Cbl C, D, - cobalamine impaired methyl and adenosylcobalamin production CblF impaired transport B12 Unresponsive Mutase defects Mut0 no mutase activity Mut+- some mutase activity

46 A Case of CblC MMA/HCYs Before treatment: Neonatal Coma requiring ventilator support With treatment No metabolic crisis Gaining milestones

47 Metabolic Acidosis from IEM Metabolic Acidosis Glycogen Storage Disease, Gluconeogenesis defect Yes Hypoglycemia? No Normal Pyruvate Dehydrogenase, Pyruvate Carboxylase Anion Gap >16 Yes +Ketones Yes Amino & Organic Acids Normal Lactate/Pyruvate No No Abnormal Elevated +Hyperchloremia : GI losses, RTA, galactosemia, +Hypoglycemia, Fatty acid oxidation defect Amino Aciduria Organic Aciduria Mitochondrial Energy Defect Chart adapted from Dr. S. Lowe

48 When Should You Consider An IEM? Newborn period Acute neurological decline Lethargy Decreased feeding Vomiting, diarrhea, dehydration Seizures Acidosis (especially if elevated anion gap) Tachypnea Hypo (or hyper) glycemia Hyperammonemia

49 Neonate s response to severe illness Respiratory distress Hypotonia Poor suck Vomiting/diarrhea Lethargy/Coma

50 Work-up of sick neonate CXR CSF Cultures Head ultrasound If the above are normal, in an infant who was initially well and then deteriorated,. THINK INBORN ERROR OF METABOLISM

51 Further Presentations Up to the seventh decade of life Recurrent syndromes Stupor, lethargy Emesis; often with dehydration Failure to thrive, poor feeding Unusual odors Sweet (MSUD), sweaty feet, barn-like Dystonia, choreoathetosis, myoclonus,hypotonia, unexplained seizures Hepatosplenomegaly MR or CP without a clear etiology

52 Less than 1:20000 How Common Are IEM? 1. More common than childhood leukemia 2. Rare as hen s teeth 3. Less than 1:10, Less than 1:20,000 20% 4% 32% 44% More common than ch... Rare as hen s teeth Less than 1:10,000

53 How Common and Why? Individually rare but collectively numerous: 1:2500 newborns Genetics Most autosomal recessive Few X-linked Pathogenesis Enzyme deficiencies Cofactor binding problems with transport, absorption, enzyme action

54 Incidence of Childhood Disorders vs. Inborn Errors of Metabolism Disease Incidence IEM Incidence Meningitis 1:3,700 Intermediary 1:4,000 Metabolism Leukemia 1:10,000 PKU 1:10,000 Retinoblastoma 1:20,000 MMA 1:20,000 JRA 1:40,000 Galactosemia 1:35,000 CNS Tumor 1:42,000 Urea Cycle Defects 1:70,000 Chronic Renal Failure 1:100,000 MSUD 1:100,000

55 History and Physical Findings Suggestive of IEM History Aversion to specific foods Untoward reaction to childhood illnesses Psychomotor retardation Growth failure Pertinent family historyconsanguinity Early neonatal deaths Physical Findings Rapid breathing Exfoliative dermatitis Seizures and/or coma often with hypotonia Unusual odor Hepatomegaly Cataracts Microcephaly

56 ED Presentation Review of 53 pediatric patients who presented to the ED and ultimately were diagnosed with IEM 85% presented with neurological signs 58% presented with GI complaints 51% presented with both neuro and GI Diagnostic approach to inborn errors of metabolism in an emergency unit.pediatric Emergency Care. 16(6): , December 2000.CALVO, M. MD, PhD; ARTUCH, R. MD, PhD; MACIA, E. MD; LUACES, C. MD, PhD; VILASECA, M. A. PhD; POU, J. MD, PhD; PINEDA, M. MD, PhD

57 Keep Your Index of Suspicion High for IEM Obtain labs during acute episode CBC with differential and platelets Chemistries (lytes, ABG, Mg, Ca, LFT, Glucose, ammonia, lactate, U/A with Ketones) Metabolic labs (amino acids plasma, urine, CSF?, plasma acylcarnitine, urine organic acids, urine acylglycine, urine orotic acid Freeze urine and plasma for further studies

58 Summer Camp Escapade An 8 year old went to sleep-away camp for the first time. After several days she became increasing lethargic and was brought to a local ED. On arrival she was barely arousable. She was afebrile, with normal vital signs. The physical examination was unremarkable. Laboratory studies were normal with the exception of ammonia which was 350. Transferred to tertiary pediatric center

59 Urea Cycle Defect Reye Syndrome Suspected Diagnosis? 1. Tick-borne encephalitis 2. New onset seizure disorder 3. Reye Syndrome 4. Urea Cycle Defect 0% 0% 0% 100% Tick-borne encephalitis New onset seizure di...

60 Past Medical History Recurrent episodes of vomiting as toddler Soft neurological findings and learning disability Hospitalized in infancy twice with gastroenteritis and dehydration. Took longer than usual to recover Learning disability Picky eater likes sweets and pasta, dislikes milk and meat Ate more at camp due to policy of eat all foods on your plate and ask for more of what you like

61 Does this change your diagnosis? What other labs would you like to see? 1. Amino acids 2. Organic Acids 3. Ketones 4. Acylcarnitine profile 5. Amino acids and organic acids 19% 0% 5% Amino acids Organic Acids 71% 5% Ketones Acylcarnitine profile Amino acids and orga...

62 Hyperammonemia Inherited Disorders Urea cycle defects Defects of urea cycle intermediate transport (HHH, LPI) Organic Acidurias FAOD Acquired Disorders Transient hyperammonemia of the newborn Reye Syndrome Liver Failure Valproate therapy Infection with urease positive bacteria Leukemia therapy Severe systemic illness

63 Back to Patient: Additional Laboratory Studies Amino acids increased glutamine Organic acids increased orotic acid Diagnosis: Partial Ornithine transcarbamoylase deficiency (OTC)

64 The Urea Cycle

65 Urea Cycle Disorders - Neonatal Presentation Normal at birth Develop poor feeding, vomiting, lethargy, irritability, tachypnea after protein feed (about 24 hrs) Same presentation as Sepsis Respiratory alkalosis Family history of unexplained neonatal death

66 Urea Cycle - Infantile Presentation to Adult Variable anorexia, lethargy, failure to thrive, migraine/headache Mental status change after protein Self selected low protein diet Normal Developmental delay Irritability, behavior problems Intermittent encephalopathy

67 OTC Deficiency X-Linked Urea Cycle Defect In Males Severe defect neonatal coma massive hyperammonemia Partial defect later onset variable hyperammonemia In Females May or may not be symptomatic depending on Lyonization Often avoid protein

68 Genetic Hyperammonemia Differential ALKALOSIS primary urea cycle defect ACIDOSIS organic acidemia, mitochondrial, lactic acidosis HYPOGLYCEMIA CARDIAC +/- LIVER +/-,MUSCLE +/- FAOD

69 Treatment Stop all protein intake Maintain Anabolism high glucose infusion with insulin (If FAOD not suspected add Lipid) Remove Ammonia Hemodialysis Activate alternate pathways sodium benzoate, sodium phenylacetate, arginine/ citrulline (Ammonul) Correct acidosis, fluid and electrolyte balance

70 College Binge? An 18 year old college student was brought to the ED disoriented. She had been at a prefinal party with friends where alcohol was served. Friends reported that she didn t eat all day because she didn t want to gain weight from the party. She got to the party had one drink and became disoriented and ataxic. They brought her to the ED. She swore she only had one drink.

71 Initial Findings Vital Signs: Pulse 100, Respiration 20, Blood pressure 70/20, Temp: 98.6 General: drowsy but arousable Neuro: ataxic gait CT scan (head) normal Electrolytes: CO 2 18 Anion gap 19 Uric acid=11.2 U/A neg.

72 IEM Drugs Post-ictal state Suspected Diagnosis 1. Alcohol intoxication 2. Drugs 3. Post-ictal state 4. IEM 0% 4% 0% 96% Alcohol intoxication

73 Received a liter of NS with dextrose with improvement of BP and mental status Blood alcohol within legal limit Tox screen - negative

74 What do we know? Fasted Ataxia and stupor Hypotension Alcohol within legal limit No glucose obtained initially but improved with glucose infusion Acidosis Increased uric acid

75 Assuming a metabolic disease is likely what tests should be ordered? 1. Acylcarnitine profile 67% 2. Amino acids 3. Porphyrins 4. Purines and pyrimidines 13% 0% 21% Acylcarnitine profile Amino acids Porphyrins Purines and pyrimidines

76 Tests you would order? Acylcarnitine profile increased C8 Urine Organic Acid increased dicarboxylic acids (adipic, suberic, sebacic), hexanoylglycine Consistent with MCAD deficiency

77 FAOD Hypoglycemia, lethargy, hepatomegaly, cardiomyopathy, liver failure, arrhythmia Lab Findings: no ketosis, CK, Uric Acid Acute Treatment: Glucose infusion mg/kg/min til stable, then Continuous enteral feeding low-fat, high glucose, normal protein L carnitine 100 mg/kg/day (controversial and should be avoided in long chain disorders)

78 Chronic Treatment of Fatty Acid Oxidation Defect Avoid fasting!!! Frequent carbohydrate meals When ill institute emergency protocol Oral hydration if possible (not vomiting, good appetite) IV D10 solution 1.5 x maintenance May decompensate rapidly err on the side of treatment

79 MCAD Most common inherited disorder of fatty acid metabolism If undiagnosed, mortality rate of 25% Autosomal recessive transmission MCAD is necessary for mitochondrial beta-oxidation of fatty acids

80 MCAD Presentation Classic presentations SIDs/near-miss SIDs Vomiting and lethargy after a period of fasting in a child 3-15 months of age Few present after 4 years of life Decompensate from fasting, febrile illness, stressors (surgery), or alcohol consumption triggers a Reye s syndrome like illness

81 Newborn Screening Revolution Tandem Mass Spectrometry (MS/MS) Organic acidopathies Amino acidopathies Fatty acid metabolism

82 MS/MS: Sorts and counts

83

84 Newborn Screening: NJ 54 disorders by MS/MS & other technologies Fatty acid oxidation disorders Organic Acidemias Urea Cycle Defects Amino acid disorders Biotinidase CAH CF Galactosemia Hemoglobinopathies Hypothyroidism

85

86 LCHAD LCHAD.htm Sisters with propionic acidemia ( Glutatic Acidemia I ( es/nikkiga1.php)

87 General Emergency Management for Suspected IEM Maintain ventilation and circulation Avoid catabolism high glucose infusion 7-10 mg/kg/min (D X Maintenance) Stop intake of potential toxin Correct Electrolytes Correct acidosis R/O Infection/treat Consult/Transfer Metabolic Center

88 Some Specific Management of Suspected IEM Prevent catabolism IV Glucose 7-10 mg/kg/min +/- intralipid 2 g/kg/d (if FAOD not suspected) Hyperammonemia Suspected Urea Cycle Defect 250 mg/kg arginine over 90 min, then 250 mg/kg/d via central line 250 mg/g NaBenzoate/NaPhenylacetate (ammonul) load IV over min via central line, then 250 mg/kg/d hemodialysis Ketotic Hypoglycemia Suspected Organic Acidemia 50 mg/kg levocarnitine IV loading; mg/kg/24 hr 1 mg B12 IM (hydroxy B12) Biotin 10 mg PO Hypoketotic Hypoglycemia Suspected FAOD Avoid lipid Avoid fasting Provide glucose IV or enteral feeding

89 Toxin Removal Consider for intoxication states (branch chain organic acidurias, urea cycle defects) Exchange transfusion least effective Peritoneal dialysis mg/kg dialysate, 15 min fill, 30 min dwell, 15 min drainage over hrs. Simple but complicated by poor drainage, leakage of dialysate, risk of overhydration Hemodialysis most effective

90 Vitamin Cofactors Biotin mg/day Carnitine mg po, 400 mg IV 100 mg po, iv Cobalamin, B mg/day Folinic acid mg/day Pyridoxine mg/day Riboflavin mg/day Thiamine, B mg/day Propionic, MCD, PC BCOA, Primary hyperammonemia, hyperlacticacidemia FAOD MMA Folinic acid responsive sx Pyridoxine responsive sx Glutaric acidemia, FAOD MSUD, hyperlacticacidemia

91 Hyperammonemia Lab findings: ammonia >400 μmol/l respiratory alkalosis May have significant handicap despite treatment Treatment: Hemodialysis High energy, protein-free nutrition When NH 3 < 150 add protein (iv amino acids) Sodium benzoate 250 mg/kg load over min and 250 mg/kg/day; sodium phenylbutyrate 250 mg/kg load over min and 250 mg/kg/day (Ammonul = 10% solution of above) L arginine 200 mg/kg/day iv L-carnitine 400 mg IV

92 REMEMBER. Inborn Errors of Metabolism Individually rare.but collectively numerous. Keep your index of suspicion high.

INBORN ERRORS OF METABOLISM (IEM) IAP UG Teaching slides

INBORN ERRORS OF METABOLISM (IEM) IAP UG Teaching slides INBORN ERRORS OF METABOLISM (IEM) 1 OBJECTIVES What are IEMs? Categories When to suspect? History and clinical pointers Metabolic presentation Differential diagnosis Emergency and long term management

More information

Newborn Screen & Development Facts about the genetic diseases new since March 2006 (Excluding Cystic Fibrosis)

Newborn Screen & Development Facts about the genetic diseases new since March 2006 (Excluding Cystic Fibrosis) Newborn Screen & Development Facts about the genetic diseases new since March 2006 (Excluding Cystic Fibrosis) 1) Argininosuccinic acidemia (ASA) a) Incidence: ~1 in 70,000 b) Deficiency in an enzyme of

More information

THE ED APPROACH OF THE CHILD WITH SUSPECTED METABOLIC DISEASE

THE ED APPROACH OF THE CHILD WITH SUSPECTED METABOLIC DISEASE THE ED APPROACH OF THE CHILD WITH SUSPECTED METABOLIC DISEASE Dr. Nadeem Qureshi M.D, FAAP, FCCM Associate Professor Pediatrics School of Medicine. St Louis University Attending Physician Pediatric Emergency

More information

Methylmalonic aciduria

Methylmalonic aciduria Methylmalonic aciduria Introductory information Written by: F. Hörster, S. Kölker & P. Burgard Reviewed & Revised for North America by: S. van Calcar Methylmalonic aciduria MMA 2 Methylmalonic aciduria

More information

Inborn Errors of Metabolism (IEM)

Inborn Errors of Metabolism (IEM) Clinical Presentation Inborn Errors of Metabolism (IEM) Click on the following: - Clinical Pearl - link to movie clip - link to picture Investigations Blood Work Urine No Acidosis NH 4 + Metabolic Acidosis

More information

Newborn Screening & Methods for Diagnosing Inborn Errors of Metabolism

Newborn Screening & Methods for Diagnosing Inborn Errors of Metabolism Newborn Screening & Methods for Diagnosing Inborn Errors of Metabolism Patricia Jones, PhD DABCC FACB UT Southwestern Medical Center Children s Medical Center Dallas, Texas Learning Objectives Justify

More information

The spectrum and outcome of the. neonates with inborn errors of. metabolism at a tertiary care hospital

The spectrum and outcome of the. neonates with inborn errors of. metabolism at a tertiary care hospital The spectrum and outcome of the neonates with inborn errors of metabolism at a tertiary care hospital Dr. Sevim Ünal Neonatology Division, Ankara Children s Hematology Oncology Research Hospital, Ankara,

More information

Metabolic Disorders. Chapter Thomson - Wadsworth

Metabolic Disorders. Chapter Thomson - Wadsworth Metabolic Disorders Chapter 28 1 Metabolic Disorders Inborn errors of metabolism group of diseases that affect a wide variety of metabolic processes; defective processing or transport of amino acids, fatty

More information

Introduction to Organic Acidemias. Hilary Vernon, MD PhD Assistant Professor of Genetic Medicine Johns Hopkins University 7.25.

Introduction to Organic Acidemias. Hilary Vernon, MD PhD Assistant Professor of Genetic Medicine Johns Hopkins University 7.25. Introduction to Organic Acidemias Hilary Vernon, MD PhD Assistant Professor of Genetic Medicine Johns Hopkins University 7.25.2014 A Brief Historical Overview Garrod, Archibald E. 1902. The Incidence of

More information

Inborn Errors of Metabolism in the Emergency Department. Will Davies June 2014

Inborn Errors of Metabolism in the Emergency Department. Will Davies June 2014 Inborn Errors of Metabolism in the Emergency Department Will Davies June 2014 Inborn Errors of Metabolism in the Emergency Department Overview Although individually rare, altogether they are 1:1000-2500

More information

Suspected Metabolic Disease in the Newborn Period Acute Management "What do I do?" Barbara Marriage, PhD RD Abbott Nutrition

Suspected Metabolic Disease in the Newborn Period Acute Management What do I do? Barbara Marriage, PhD RD Abbott Nutrition Suspected Metabolic Disease in the Newborn Period Acute Management "What do I do?" Barbara Marriage, PhD RD Abbott Nutrition Introduction Review clinical findings that may be suspicious of a metabolic

More information

Work-Up and Initial Management of Common Metabolic Emergencies in the Inpatient Setting

Work-Up and Initial Management of Common Metabolic Emergencies in the Inpatient Setting Work-Up and Initial Management of Common Metabolic Emergencies in the Inpatient Setting Kristin Lindstrom, MD Division of Genetics and Metabolism Phoenix Children s Hospital AzAAP Pediatrics in the Red

More information

Organic acidaemias (OAs) & Urea cycle disorders (UCDs) PRESENTATION & MANAGEMENT

Organic acidaemias (OAs) & Urea cycle disorders (UCDs) PRESENTATION & MANAGEMENT Great Ormond Street Hospital London 20/04/2018 Organic acidaemias (OAs) & Urea cycle disorders (UCDs) PRESENTATION & MANAGEMENT Spyros P. Batzios, MD, MSc, PhD OAs & UCDs How do they present? neonatal

More information

3 HYDROXY 3 METHYLGLUTARYL CoA (3 HMG CoA) LYASE DEFICIENCY RECOMMENDATIONS ON EMERGENCY MANAGEMENT OF METABOLIC DISEASES

3 HYDROXY 3 METHYLGLUTARYL CoA (3 HMG CoA) LYASE DEFICIENCY RECOMMENDATIONS ON EMERGENCY MANAGEMENT OF METABOLIC DISEASES 3 HYDROXY 3 METHYLGLUTARYL CoA (3 HMG CoA) LYASE DEFICIENCY RECOMMENDATIONS ON EMERGENCY MANAGEMENT OF METABOLIC DISEASES Patient s name: Date of birth: Please read carefully. Meticulous and prompt treatment

More information

UREA CYCLE DISORDERS - The What, Why, How and When

UREA CYCLE DISORDERS - The What, Why, How and When UREA CYCLE DISORDERS - The What, Why, How and When George A. Diaz, MD, PhD Program for Inherited Metabolic Diseases Department of Genetics and Genomic Sciences Department of Pediatrics Icahn School of

More information

Inborn Errors of Metabolism. Metabolic Pathway. Digestion and Fasting. How is Expanded Newborn Screening Different? MS/MS. The body is a factory.

Inborn Errors of Metabolism. Metabolic Pathway. Digestion and Fasting. How is Expanded Newborn Screening Different? MS/MS. The body is a factory. Inborn Errors of Metabolism The body is a factory. Inborn errors of metabolism are rare genetic disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects

More information

ANATOMY OF A METABOLIC CRISIS: FAOD-style. Mark S. Korson, MD Tufts Medical Center Boston, MA

ANATOMY OF A METABOLIC CRISIS: FAOD-style. Mark S. Korson, MD Tufts Medical Center Boston, MA ANATOMY OF A METABOLIC CRISIS: FAOD-style Mark S. Korson, MD Tufts Medical Center Boston, MA NORMAL PHYSIOLOGY Anabolic Eating well Calories eaten > body s needs BRAIN uses GLUCOSE MUSCLE uses GLUCOSE

More information

Guideline for the diagnosis and management of isovaleryl-coa-dehydrogenase deficiency (isovaleric acidemia) - a systematic review -

Guideline for the diagnosis and management of isovaleryl-coa-dehydrogenase deficiency (isovaleric acidemia) - a systematic review - Guideline for the diagnosis and management of isovaleryl-coa-dehydrogenase deficiency (isovaleric acidemia) - a systematic review - Guideline development group International interdisciplinary guideline

More information

Clinical Management of Organic Acidemias and OAA Natural History Registry. Kim Chapman MD PhD Children s National Rare Disease Institute

Clinical Management of Organic Acidemias and OAA Natural History Registry. Kim Chapman MD PhD Children s National Rare Disease Institute Clinical Management of Organic Acidemias and OAA Natural History Registry Kim Chapman MD PhD Children s National Rare Disease Institute Disclosure Nothing to disclose concerning this lecture Organic acid?

More information

Acute Management of Sick Infants with Suspected Inborn Errors of Metabolism

Acute Management of Sick Infants with Suspected Inborn Errors of Metabolism Indian J Pediatr (July 2011) 78(7):854 859 DOI 10.1007/s12098-011-0422-0 SYMPOSIUM ON PICU PROTOCOLS OF AIIMS Acute Management of Sick Infants with Suspected Inborn Errors of Metabolism Neerja Gupta Madhulika

More information

So Much More Than The PKU Test

So Much More Than The PKU Test Newborn Metabolic Screening So Much More Than The PKU Test Sarah Viall, MSN, PPCNP BC Newborn Screening Program Coordinator Division of Genetics & Metabolism Conflicts of Interest I have no conflicts of

More information

Medical Foods for Inborn Errors of Metabolism

Medical Foods for Inborn Errors of Metabolism Medical Foods for Inborn Errors of Metabolism Policy Number: Original Effective Date: MM.02.014 02/18/2000 Line(s) of Business: Current Effective Date: HMO; PPO; QUEST 08/23/2013 Section: Medicine Place(s)

More information

Routine Newborn Screening, Testing the Newborn Inherited Metabolic Disorders Update August 2015

Routine Newborn Screening, Testing the Newborn Inherited Metabolic Disorders Update August 2015 Routine Newborn Screening, Testing the Newborn Inherited Metabolic Disorders Update August 2015 Metabolic birth defects can cause physical problems, mental retardation and, in some cases, death. It is

More information

Newborn Screening in Manitoba. Information for Health Care Providers

Newborn Screening in Manitoba. Information for Health Care Providers Newborn Screening in Manitoba Information for Health Care Providers Newborn screening: a healthy start leads to a healthier life Health care professionals have provided newborn screening for phenylketonuria

More information

Urea Cycle Defects. Dr Mick Henderson. Biochemical Genetics Leeds Teaching Hospitals Trust. MetBioNet IEM Introductory Training

Urea Cycle Defects. Dr Mick Henderson. Biochemical Genetics Leeds Teaching Hospitals Trust. MetBioNet IEM Introductory Training Urea Cycle Defects Dr Mick Henderson Biochemical Genetics Leeds Teaching Hospitals Trust The Urea Cycle The urea cycle enables toxic ammonia molecules to be converted to the readily excreted and non toxic

More information

TITLE: NURSING GUIDELINES FOR THE MANAGEMENT OF CHILDREN WITH METHYLMALONIC ACIDURIA. Eilish O Connell, Clinical Education Facilitator, NCIMD

TITLE: NURSING GUIDELINES FOR THE MANAGEMENT OF CHILDREN WITH METHYLMALONIC ACIDURIA. Eilish O Connell, Clinical Education Facilitator, NCIMD NO. OF PAGES: Page 1 of 17 SUPERCEDES: N/A NURSING GUIDELINES FOR THE MANAGEMENT OF CHILDREN WITH METHYLMALONIC ACIDURIA NAME/ Eilish O Connell, Clinical Education Facilitator, NCIMD SIGNATURE: DATE: NAME/

More information

Fatty Acid Oxidation Disorders Organic Acid Disorders

Fatty Acid Oxidation Disorders Organic Acid Disorders Genetic Fact Sheets for Parents Fatty Acid Oxidation Disorders Organic Acid Disorders Screening, Technology, and Research in Genetics is a multi-state project to improve information about the financial,

More information

Organic Acid Disorders

Organic Acid Disorders Genetic Fact Sheets for Parents Organic Acid Disorders Screening, Technology, and Research in Genetics is a multi-state project to improve information about the financial, ethical, legal, and social issues

More information

Training Syllabus CLINICAL SYLLABUS

Training Syllabus CLINICAL SYLLABUS Training Syllabus CLINICAL SYLLABUS SYLLABUS FOR TRAINING IN CLINICAL PAEDIATRIC METABOLIC MEDICINE Updated July 2006 This syllabus is intended as a guide. Whilst the training should be comprehensive,

More information

HA Convention 2016 Master course How to Handle Abnormal Newborn Metabolic Screening Results Causes, Management and Follow up

HA Convention 2016 Master course How to Handle Abnormal Newborn Metabolic Screening Results Causes, Management and Follow up HA Convention 2016 Master course How to Handle Abnormal Newborn Metabolic Screening Results Causes, Management and Follow up Dr. Josephine Chong Clinical Professional Consultant Centre of Inborn Errors

More information

Newborn Screening: Blood Spot Disorders

Newborn Screening: Blood Spot Disorders Newborn Screening: Blood Spot Disorders Arizona s Newborn Screening Program Program Overview Panel of Disorders Disorder Descriptions Program Components Hospitals ADHS Lab ADHS Follow-up ADHS Billing Medical

More information

Metabolic Emergencies and the Pediatrician

Metabolic Emergencies and the Pediatrician Metabolic Emergencies and the Pediatrician Stephen G. Kahler, MD Professor of Pediatrics Section of Genetics and Metabolism, UAMS and ACH Hot Springs, AR March 8, 2012 INHERITED METABOLIC DISORDERS HOW

More information

For healthcare professionals Methylmalonic Acidurias

For healthcare professionals Methylmalonic Acidurias www.e-imd.org For healthcare professionals Methylmalonic Acidurias Methylmalonic acidurias (MMAurias) comprise a group of inborn errors of metabolism characterized by an isolated accumulation of methylmalonic

More information

Positive Newborn Screens: What do you do next?

Positive Newborn Screens: What do you do next? Positive Newborn Screens: What do you do next? James B. Gibson, MD, Ph.D. Biochemical Geneticist at Specially for Children Clinical Associate Professor of Pediatrics UTHSCSA Carla R. Scott, MD Pediatric

More information

Fatty Acid Oxidation Disorders

Fatty Acid Oxidation Disorders Genetic Fact Sheets for Parents Fatty Acid Oxidation Disorders Screening, Technology, and Research in Genetics is a multi-state project to improve information about the financial, ethical, legal, and social

More information

ESPEN Congress Madrid 2018

ESPEN Congress Madrid 2018 ESPEN Congress Madrid 2018 Inborn Errors Of Metabolism Urea Cycle Disorders Diagnosis And Care F. Feillet (FR) Urea cycle disorders, diagnosis and care F Feillet National reference centre for Inborn errors

More information

Lynne A. Wolfe, MS, ACNP, PNP, BC Department of Genetics Yale School of Medicine

Lynne A. Wolfe, MS, ACNP, PNP, BC Department of Genetics Yale School of Medicine Lynne A. Wolfe, MS, ACNP, PNP, BC Department of Genetics Yale School of Medicine Harvey Levy, MD Mark Korson, MD Piero Rinaldo, MD, PhD Larry Sweetman, PhD K. Michael Gibson, PhD Charlie Roe, MD Jerry

More information

ARGININOSUCCINIC ACIDEMIA (or ARGININOSUCCINATE LYASE DEFICIENCY) RECOMMENDATIONS ON EMERGENCY MANAGEMENT OF METABOLIC DISEASES

ARGININOSUCCINIC ACIDEMIA (or ARGININOSUCCINATE LYASE DEFICIENCY) RECOMMENDATIONS ON EMERGENCY MANAGEMENT OF METABOLIC DISEASES ARGININOSUCCINIC ACIDEMIA (or ARGININOSUCCINATE LYASE DEFICIENCY) RECOMMENDATIONS ON EMERGENCY MANAGEMENT OF METABOLIC DISEASES Patient s name: Date of birth: Please read carefully. Meticulous and prompt

More information

Fatty Acid Oxidation Disorders

Fatty Acid Oxidation Disorders Genetic Fact Sheets for Parents Fatty Acid Oxidation Disorders Screening, Technology, and Research in Genetics is a multi-state project to improve information about the financial, ethical, legal, and social

More information

For Your Baby s Health Department of Health

For Your Baby s Health Department of Health Newborn Screening For Your Baby s Health Department of Health Why is my baby tested? To help make sure your baby will be as healthy as possible. The blood test provides important information about your

More information

Module : Clinical correlates of disorders of metabolism Block 3, Week 2

Module : Clinical correlates of disorders of metabolism Block 3, Week 2 Module : Clinical correlates of disorders of metabolism Block 3, Week 2 Department of Paediatrics and Child Health University of Pretoria Tutor : Prof DF Wittenberg : dwittenb@medic.up.ac.za Aim of this

More information

Isovaleric Acidemia: Quick reference guide

Isovaleric Acidemia: Quick reference guide Isovaleric Acidemia: Quick reference guide Introduction Isovaleric acidemia (IVA) is an inborn error of the leucine pathway caused by defects of the isovaleryl-oadehydrogenase (IV). The clinical presentation

More information

SYLLABUS FOR TRAINING IN CLINICAL PAEDIATRIC METABOLIC MEDICINE

SYLLABUS FOR TRAINING IN CLINICAL PAEDIATRIC METABOLIC MEDICINE SYLLABUS FOR TRAINING IN CLINICAL PAEDIATRIC METABOLIC MEDICINE Updated December 2014: Vassili Valayannopoulos and Andrew Morris Paediatrics is an independent medical specialty based on the knowledge and

More information

Metabolic Changes in ASD. Norma J. Arciniegas, MD Simón E. Carlo, MD Instituto Filius

Metabolic Changes in ASD. Norma J. Arciniegas, MD Simón E. Carlo, MD Instituto Filius Metabolic Changes in ASD Norma J. Arciniegas, MD Simón E. Carlo, MD Instituto Filius 12 patients 3 Autism: Ages 3/3/3.7 3 PDD: Ages 3/3/6 3 Asperger: Ages 6/7/15.1 3 Speech delay and Sensory Problems (SHL):

More information

Carnitine palmitoyl transferase 2 deficiency (CPT2) is a rare inherited disorder that occurs when

Carnitine palmitoyl transferase 2 deficiency (CPT2) is a rare inherited disorder that occurs when CPT2 Deficiency Carnitine palmitoyl transferase 2 deficiency (CPT2) is a rare inherited disorder that occurs when the last step in the entry of fats into sac-like bodies called mitochondria is blocked.

More information

Inborn Errors of Metabolism Clinical Approach to Diagnosis and Treatment

Inborn Errors of Metabolism Clinical Approach to Diagnosis and Treatment Case Scenario: 15 year old girl presented in ED with aggressive behaviour and hallucinations. No associated fever, vomiting, seizures or developmental concerns Previously well Inborn Errors of Metabolism

More information

LOW CITRULLINE AS A MARKER FOR THE PROXIMAL UREA CYCLE DEFECTS EXPERIENCE OF THE NEW ENGLAND NEWBORN SCREENING PROGRAM

LOW CITRULLINE AS A MARKER FOR THE PROXIMAL UREA CYCLE DEFECTS EXPERIENCE OF THE NEW ENGLAND NEWBORN SCREENING PROGRAM LOW CITRULLINE AS A MARKER FOR THE PROXIMAL UREA CYCLE DEFECTS EXPERIENCE OF THE NEW ENGLAND NEWBORN SCREENING PROGRAM Inderneel Sahai, MD, FACMG Newborn Screening and Genetic Testing Symposium Oct 2014

More information

Fatty Acid Oxidation Disorders- an update. Fiona Carragher Biochemical Sciences, GSTS Pathology St Thomas Hospital, London

Fatty Acid Oxidation Disorders- an update. Fiona Carragher Biochemical Sciences, GSTS Pathology St Thomas Hospital, London Fatty Acid Oxidation Disorders- an update Fiona Carragher Biochemical Sciences, GSTS Pathology St Thomas Hospital, London An update. Overview of metabolism Clinical presentation and outcome Diagnostic

More information

TRANSAMINATION AND UREA CYCLE

TRANSAMINATION AND UREA CYCLE TRANSAMINATION AND UREA CYCLE USMAN SUMO FRIEND TAMBUNAN ARLI ADITYA PARIKESIT SEPTIANA BIOINFORMATICS GROUP DEPARTEMENT OF CHEMISTRY FACULTY OF MATHEMATIC AND SCIENCE UNIVERSITY OF INDONESIA What is transamination?

More information

Col Rama Krishna Sanjeev Military Hospital Chennai Prof Shanmughasundaram Mehta Hospital, Chennai

Col Rama Krishna Sanjeev Military Hospital Chennai Prof Shanmughasundaram Mehta Hospital, Chennai Col Rama Krishna Sanjeev Military Hospital Chennai Prof Shanmughasundaram Mehta Hospital, Chennai 11 day old male neonate admitted on 26/6 to our Hospital with c/olethargy -since day1 abnormal movements

More information

BIOTIN (BIOTINIDASE) DEFICIENCY Marc E. Tischler, PhD; University of Arizona

BIOTIN (BIOTINIDASE) DEFICIENCY Marc E. Tischler, PhD; University of Arizona BIOTIN (BIOTINIDASE) DEFICIENCY Marc E. Tischler, PhD; University of Arizona BIOTIN (BIOTINIDASE) DEFICIENCY biotin in the body is recycled by its removal from carboxylase enzymes to which it is attached

More information

Metabolic Precautions & ER Recommendations

Metabolic Precautions & ER Recommendations Metabolic Precautions & ER Recommendations * To whom correspondence Sumit Parikh, should MD be addressed Center for Pediatric Neurology Cleveland Clinic Cleveland, OH UMDF 2010 The catabolic state Entering

More information

Contribution of Nutrients in Complex Inborn Errors of Metabolism: The Case of Methylmalonic Aciduria (MMA)

Contribution of Nutrients in Complex Inborn Errors of Metabolism: The Case of Methylmalonic Aciduria (MMA) Contribution of Nutrients in Complex Inborn Errors of Metabolism: The Case of Methylmalonic Aciduria (MMA) Charles P. Venditti, MD, PhD Head, Organic Acid Research Section No conflicts of interest to declare

More information

National Metabolic Biochemistry Network Guidelines for the investigation of hypoglycaemia in infants and children

National Metabolic Biochemistry Network Guidelines for the investigation of hypoglycaemia in infants and children National Metabolic Biochemistry Network Guidelines for the investigation of hypoglycaemia in infants and children Aim To provide guidance on the biochemical investigation of hypoglycaemia in infants and

More information

Organic Acid Disorders

Organic Acid Disorders Genetic Fact Sheets for Parents Organic Acid Disorders Screening, Technology, and Research in Genetics is a multi-state project to improve information about the financial, ethical, legal, and social issues

More information

Ornithine Transcarbamylase Deficiency (OTCD) Recommendations on Emergency Management of Metabolic Disease

Ornithine Transcarbamylase Deficiency (OTCD) Recommendations on Emergency Management of Metabolic Disease Ornithine Transcarbamylase Deficiency (OTCD) Recommendations on Emergency Management of Metabolic Disease Patient s Name: Date of Birth: MRN in KFSH&RC: Please read carefully. Meticulous and prompt treatment

More information

CLINICAL SIGNS SUGGESTIVE OF A NEUROMETABOLIC DISEASE. Bwee Tien Poll-The Amsterdam UMC The Netherlands

CLINICAL SIGNS SUGGESTIVE OF A NEUROMETABOLIC DISEASE. Bwee Tien Poll-The Amsterdam UMC The Netherlands CLINICAL SIGNS SUGGESTIVE OF A NEUROMETABOLIC DISEASE Bwee Tien Poll-The Amsterdam UMC The Netherlands FRAMEWORK OF PRINCIPALS 1. Problem-oriented clinical approach 2. Biomarkers in plasma, urine, CSF

More information

Organic Acid Disorders

Organic Acid Disorders Genetic Fact Sheets for Parents Organic Acid Disorders Screening, Technology, and Research in Genetics is a multi-state project to improve information about the financial, ethical, legal, and social issues

More information

Organic Acid Disorders

Organic Acid Disorders Genetic Fact Sheets for Parents Organic Acid Disorders Screening, Technology, and Research in Genetics is a multi-state project to improve information about the financial, ethical, legal, and social issues

More information

Pediatric emergencies (SHOCK & COMA) Dr Mubarak Abdelrahman Assistant Professor Jazan University

Pediatric emergencies (SHOCK & COMA) Dr Mubarak Abdelrahman Assistant Professor Jazan University Pediatric emergencies (SHOCK & COMA) Dr Mubarak Abdelrahman Assistant Professor Jazan University SHOCK Definition: Shock is a syndrome = inability to provide sufficient oxygenated blood to tissues. Oxygen

More information

Fatty Acid Beta-Oxidation Disorders: A Brief Review

Fatty Acid Beta-Oxidation Disorders: A Brief Review Mini Review Received: July 12, 2015 Accepted: November 12, 2015 Published online: March 11, 2016 Fatty Acid Beta-Oxidation Disorders: A Brief Review Vijay A. Vishwanath Division of Pediatric Neurology,

More information

Inborn errors of metabolism

Inborn errors of metabolism ESPEN Congress Nice 2010 From child to adult nutrition Inborn errors of metabolism Pascal Crenn Inborn errors of metabolism: from child to adult Pascal Crenn Hôpital Raymond Poincaré 92380 Garches. France

More information

Nutritional Management of Inborn Errors of Metabolism. Kay Davis, RD, CSP Esther Berenhaut, RD, CSP, CSR Aug 28, 2017

Nutritional Management of Inborn Errors of Metabolism. Kay Davis, RD, CSP Esther Berenhaut, RD, CSP, CSR Aug 28, 2017 Nutritional Management of Inborn Errors of Metabolism Kay Davis, RD, CSP Esther Berenhaut, RD, CSP, CSR Aug 28, 2017 OBJECTIVES Brief overview of newborn screening of metabolic disorders, inheritance patterns.

More information

A Guide for Prenatal Educators

A Guide for Prenatal Educators A Guide for Prenatal Educators Why Teach Newborn Screening This booklet is designed to make it easy for you, a prenatal educator, to effectively inform expectant parents about newborn screening. All of

More information

The breakdown of fats to provide energy occurs in segregated membrane-bound compartments

The breakdown of fats to provide energy occurs in segregated membrane-bound compartments CPT1a deficiency The breakdown of fats to provide energy occurs in segregated membrane-bound compartments of the cell known as mitochondria. Carnitine palmitoyltransferase Ia (CPT1a) is a protein that

More information

Medium-chain acyl-coa dehydrogenase deficiency

Medium-chain acyl-coa dehydrogenase deficiency Medium-chain acyl-coa dehydrogenase deficiency Introductory information Written by: V. Prietsch & P. Burgard Reviewed & Revised for North America by: S. van Calcar Medium-chain acyl-coa dehydrogenase MCAD

More information

Very-long-chain acyl-coa dehydrogenase deficiency

Very-long-chain acyl-coa dehydrogenase deficiency Very-long-chain acyl-coa dehydrogenase deficiency Introductory information Written by: V. Prietsch & P. Burgard Reviewed & Revised for North America by: S. van Calcar Very-long-chain acyl-coa dehydrogenase

More information

Genomics & Modern Health Care Caring for the Special Children & Adults of Isolated Populations. Propionic Acidemia

Genomics & Modern Health Care Caring for the Special Children & Adults of Isolated Populations. Propionic Acidemia Genomics & Modern Health Care Caring for the Special Children & Adults of Isolated Populations Propionic Acidemia D. Holmes Morton MD Pediatrician, Clinic for Special Children Strasburg, Pennsylvania 17579

More information

Most common is the congenital adrenogenital syndrome (AGS) or congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency.

Most common is the congenital adrenogenital syndrome (AGS) or congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Newborn Screening Examination parameters: TSH-neonatal (hypothyreosis), 17-OH progesterone (AGS), galactose (galactosemia), galactose-uridyl transferase (galacto semia), biotinidase (biotinidase ), phenylalanine

More information

Jana Novotná, Bruno Sopko. Department of the Medical Chemistry and Clinical Biochemistry The 2nd Faculty of Medicine, Charles Univ.

Jana Novotná, Bruno Sopko. Department of the Medical Chemistry and Clinical Biochemistry The 2nd Faculty of Medicine, Charles Univ. Amino acid metabolism II. Urea cycle Jana Novotná, Bruno Sopko Department of the Medical Chemistry and Clinical Biochemistry The 2nd Faculty of Medicine, Charles Univ. Nitrogen balance Tissue proteins

More information

Secondary Energy Deficiencies in Organic Acidemias. Kimberly A Chapman MD PhD Children s National July 26, 2014

Secondary Energy Deficiencies in Organic Acidemias. Kimberly A Chapman MD PhD Children s National July 26, 2014 Secondary Energy Deficiencies in Organic Acidemias Kimberly A Chapman MD PhD Children s National July 26, 2014 2 Goals of this talk Describe the secondary energy deficiencies seen in organic acidemias

More information

Overview. o Limitations o Normal regulation of blood glucose o Definition o Symptoms o Clinical forms o Pathophysiology o Treatment.

Overview. o Limitations o Normal regulation of blood glucose o Definition o Symptoms o Clinical forms o Pathophysiology o Treatment. Pål R. Njølstad MD PhD KG Jebsen Center for Diabetes Research University of Bergen, Norway Depertment of Pediatrics Haukeland University Hospital Broad Institute of Harvard & MIT Cambridge, MA, USA Hypoglycemia

More information

Overview of Newborn Screening, Potential Uses of Residual Dried Blood Spots, and Protection of Privacy

Overview of Newborn Screening, Potential Uses of Residual Dried Blood Spots, and Protection of Privacy Overview of Newborn Screening, Potential Uses of Residual Dried Blood Spots, and Protection of Privacy Alan R. Fleischman, M.D. Senior Vice President and Medical Director Chair, Federal Advisory Committee,

More information

Urea Cycle Disorders Prior Authorization Program Summary

Urea Cycle Disorders Prior Authorization Program Summary Urea Cycle Disorders Prior Authorization Program Summary FDA APPROVED INDICATIONS DOSAGE 1,2 Agent(s) Indication(s) Dosing -Adjunctive therapy in the chronic management of patients with urea cycle disorders

More information

Amino Acid Oxidation and the Urea Cycle

Amino Acid Oxidation and the Urea Cycle Amino Acid Oxidation and the Urea Cycle Amino Acids: Final class of biomolecules whose oxidation contributes significantly to the generation of energy Undergo oxidation in three metabolic circumstances

More information

Inborn Errors of Metabolism

Inborn Errors of Metabolism 30 Inborn Errors of Metabolism Inborn errors of metabolism (IEM) are disorders in which there is a block in the normal metabolic pathway that is caused by a genetic defect of a specific enzyme. The number

More information

Amino Acid Disorders. What is ASAL deficiency? Genetic Fact Sheets for Parents

Amino Acid Disorders. What is ASAL deficiency? Genetic Fact Sheets for Parents Genetic Fact Sheets for Parents Amino Acid Disorders Screening, Technology, and Research in Genetics is a multi-state project to improve information about the financial, ethical, legal, and social issues

More information

OVERVIEW M ET AB OL IS M OF FR EE FA TT Y AC ID S

OVERVIEW M ET AB OL IS M OF FR EE FA TT Y AC ID S LIPOLYSIS LIPOLYSIS OVERVIEW CATABOLISM OF FREE FATTY ACIDS Nonesterified fatty acids Source:- (a) breakdown of TAG in adipose tissue (b) action of Lipoprotein lipase on plasma TAG Combined with Albumin

More information

Chapter 16 Nutrition, Fluids and Electrolytes, and Acid-Base Balance Nutrition Nutrients Water o Functions Promotes metabolic processes Transporter

Chapter 16 Nutrition, Fluids and Electrolytes, and Acid-Base Balance Nutrition Nutrients Water o Functions Promotes metabolic processes Transporter Chapter 16 Nutrition, Fluids and Electrolytes, and Acid-Base Balance Nutrition Nutrients Water o Functions Promotes metabolic processes Transporter for nutrients and wastes Lubricant Insulator and shock

More information

Paediatric Clinical Chemistry

Paediatric Clinical Chemistry Paediatric Clinical Chemistry Dr N Oosthuizen Dept Chemical Pathology UP 2011 Paediatric biochemistry The child is not a miniature adult Physiological development Immature organ systems Growing individual

More information

UK NATIONAL METABOLIC BIOCHEMISTRY NETWORK GUIDELINES FOR THE INVESTIGATION OF HYPERAMMONAEMIA

UK NATIONAL METABOLIC BIOCHEMISTRY NETWORK GUIDELINES FOR THE INVESTIGATION OF HYPERAMMONAEMIA UK NATIONAL METABOLIC BIOCHEMISTRY NETWORK GUIDELINES FOR THE INVESTIGATION OF HYPERAMMONAEMIA Hyperammonaemia results from defective catabolism of amino acids to urea. Recognition and treatment of hyperammonaemia,

More information

Urea Cycle Disorders and Hyperammonemia: Diagnosable Treatable Screenable

Urea Cycle Disorders and Hyperammonemia: Diagnosable Treatable Screenable Urea Cycle Disorders and Hyperammonemia: Diagnosable Treatable Screenable Marshall L. Summar, M.D. Chief, Division of Genetics and Metabolism Children s National Medical Center Washington, DC, USA Disclosure

More information

ISOVALERIC ACIDAEMIA -ACUTE DECOMPENSATION (standard version)

ISOVALERIC ACIDAEMIA -ACUTE DECOMPENSATION (standard version) Contact Details Name: Hospital Telephone: This protocol has 5 pages ISOVALERIC ACIDAEMIA -ACUTE DECOMPENSATION (standard version) Please read carefully. Meticulous treatment is very important as there

More information

GA-1. Glutaric Aciduria Type 1. TEMPLE Tools Enabling Metabolic Parents LEarning. Information for families after a positive newborn screening

GA-1. Glutaric Aciduria Type 1. TEMPLE Tools Enabling Metabolic Parents LEarning. Information for families after a positive newborn screening Glutaric Aciduria Type 1 GA-1 Information for families after a positive newborn screening Adapted by the Dietitians Group BIMDG British Inherited Metabolic Diseases Group BASED ON THE ORIGINAL TEMPLE WRITTEN

More information

NEONATAL SEIZURES-PGPYREXIA REVIEW

NEONATAL SEIZURES-PGPYREXIA REVIEW NEONATAL SEIZURES-PGPYREXIA REVIEW This is a very important Postgraduate topics will few Q asked in undergraduation also. Lets see them in detail. References: 1.Volpe s Neurology of newborn 2.Nelson s

More information

UPDATE ON UREA CYCLE DISORDERS TREATMENT

UPDATE ON UREA CYCLE DISORDERS TREATMENT UPDATE ON UREA CYCLE DISORDERS TREATMENT George A. Diaz, MD, PhD Program for Inherited Metabolic Diseases Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai Disclosure

More information

Medical Policy An independent licensee of the Blue Cross Blue Shield Association

Medical Policy An independent licensee of the Blue Cross Blue Shield Association Urea Cycle Disorders Page 1 of 7 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Urea Cycle Disorders Prime Therapeutics will review Prior Authorization requests

More information

Metabolic diseases of the liver

Metabolic diseases of the liver Metabolic diseases of the liver Central role in metabolism Causes and mechanisms of dysfunction Clinical patterns of metabolic disease Clinical approach to problem-solving Specific disorders Liver s central

More information

Standard of Newborn Care in the Age of Birth Plans. Stephanie Deal, MD Tiffany McKee-Garrett, MD

Standard of Newborn Care in the Age of Birth Plans. Stephanie Deal, MD Tiffany McKee-Garrett, MD Standard of Newborn Care in the Age of Birth Plans Stephanie Deal, MD Tiffany McKee-Garrett, MD Disclosure We have no relevant financial relationships with the manufacturers(s) of any commercial products(s)

More information

Salicylate (Aspirin) Ingestion California Poison Control Background 1. The prevalence of aspirin-containing analgesic products makes

Salicylate (Aspirin) Ingestion California Poison Control Background 1. The prevalence of aspirin-containing analgesic products makes Salicylate (Aspirin) Ingestion California Poison Control 1-800-876-4766 Background 1. The prevalence of aspirin-containing analgesic products makes these agents, found in virtually every household, common

More information

Nutritional Interventions in Primary Mitochondrial Disorders

Nutritional Interventions in Primary Mitochondrial Disorders Nutritional Interventions in Primary Mitochondrial Disorders Carolyn J Ellaway MBBS PhD FRACP CGHGSA Genetic Metabolic Disorders Service Sydney Children s Hospital Network Disciplines of Child and Adolescent

More information

NEONATAL HYPOGLYCEMIA HEATHER MCKNIGHT-MENCI, MSN, CRNP CHILDREN S HOSPITAL OF PHILADELPHIA

NEONATAL HYPOGLYCEMIA HEATHER MCKNIGHT-MENCI, MSN, CRNP CHILDREN S HOSPITAL OF PHILADELPHIA NEONATAL HYPOGLYCEMIA HEATHER MCKNIGHT-MENCI, MSN, CRNP CHILDREN S HOSPITAL OF PHILADELPHIA WHAT IS NEONATAL HYPOGLYCEMIA? Glucose concentration low enough to cause signs and symptoms of impaired brain

More information

Permanent neonatal diabetes mellitus. Case Report

Permanent neonatal diabetes mellitus. Case Report Rawal Medical Journal An official publication of Pakistan Medical Association Rawalpindi Islamabad branch Established 1975 Volume 36 Number 4 October - December 2011 Case Report Permanent neonatal diabetes

More information

Presentation and investigation of mitochondrial disease in children

Presentation and investigation of mitochondrial disease in children Presentation and investigation of mitochondrial disease in children Andrew Morris Willink Unit, Manchester Mitochondrial function Carbohydrate Fat Respiratory chain Energy Mitochondria are the product

More information

Glycogen Storage Disease

Glycogen Storage Disease Glycogen Storage Disease 1 Introduction The food we eat is usually used for growth, tissue repair and energy. The body stores what it does not use. Excess sugar, or glucose, is stored as glycogen in the

More information

Genética e Hígado: Cómo contribuye la genética en el algoritmo diagnóstico de la enfermedad hepática pediátrica? Nicholas Ah Mew, MD

Genética e Hígado: Cómo contribuye la genética en el algoritmo diagnóstico de la enfermedad hepática pediátrica? Nicholas Ah Mew, MD Genética e Hígado: Cómo contribuye la genética en el algoritmo diagnóstico de la enfermedad hepática pediátrica? Nicholas Ah Mew, MD April 24, 2017 SAP 2017 Buenos Aires Genetic disorders are rare why

More information

Basal Ganglia Involvement in Mitochondrial Acetoacetyl-CoA Thiolase deficiency (T2).

Basal Ganglia Involvement in Mitochondrial Acetoacetyl-CoA Thiolase deficiency (T2). Basal Ganglia Involvement in Mitochondrial Acetoacetyl-CoA Thiolase deficiency (T2). Stéphanie Paquay Robert Debré Hospital Reference Center For Metabolic Diseases Paris, France Mitochondrial Acetoacetyl-CoA

More information

Beyond the case for NBS in South Africa. Chris Vorster 28/05/2016

Beyond the case for NBS in South Africa. Chris Vorster 28/05/2016 Beyond the case for NBS in South Africa Chris Vorster 28/05/2016 The case for NBS in SA Economic justification Cost Utility analysis = Cost/QALY GDP/Capita Immediate implementation (WHO) Political justification

More information

Attachment 1. Newborn Screening Program Description

Attachment 1. Newborn Screening Program Description Attachment 1 Newborn Screening Program Description The core mission of Texas Newborn Screening Program is to save children s lives through the early detection of life-threatening disorders. 34 Newborn

More information