Neurodegenerative disorders: an approach to investigation. Robert Robinson Practical Paediatric Neurology Study Days April 2018
|
|
- Amanda Ferguson
- 5 years ago
- Views:
Transcription
1 Neurodegenerative disorders: an approach to investigation Robert Robinson Practical Paediatric Neurology Study Days April 2018
2 Aims An approach to investigating and diagnosing young children with progressive encephalopathies Targeted investigations according to Age of presentation Predominant neurological signs Presence of additional specific features Overlap with other talks
3 Overview Approach to diagnosis Neonatal encephalopathies Late infantile motor deficits Leukodystrophy
4 Progressive neurological (neurodegenerative) disorders Progressive (irreversible) deterioration >3 months with Loss of attained intellectual or developmental abilities and Cognitive Motor Development of abnormal neurological signs Spasticity, ataxia, dystonia, hypotonia, weakness Epilepsy Visual, hearing impairment
5 Causes of neurodegenerative disorders Epileptic encephalopathies Neuromuscular disorders Hydrocephalus Cerebrovascular disorders CNS tumours Chronic CNS inflammation and infection Progressive neurogenetic/neurometabolic encephalopathies
6 Prevalence rates Progressive encephalopathies 0.5/1000 Central motor deficit (= CP) 2/1000 Epilepsy 5/1000 Severe intellectual disability 5/1000 CNS tumours 0.05/1000 Duchenne muscular dystrophy 0.12/1000
7 Approach to diagnosis - 1 Age of presentation Neonatal & Early infantile (<1 year); Late infantile/early juvenile (1-5); (+ 5y ) Juvenile and adult Establish if static or progressive disorder
8 Developmental trajectories
9 Approach to diagnosis - 2 By predominant symptoms: Motor deficit: spastic, dystonic, ataxic, neuropathic, mixed, Dementia Epilepsy Defect of special senses Presence of specific features ( handles ) e.g.: Macro/microcephaly; Dysmorphic features; Cutaneous; Ocular; Coma; Dystonia
10 Always consider treatable causes of progressive neurological disease Epilepsy Autistic regression Infection Hydrocephalus Tumour Nutritional deficiencies eg B12 Abusive and factitious illness
11 Case example 1
12 Neonatal encephalopathy with seizures A 10 day old baby Hypotonic since birth Onset of seizures at 4 days No evidence of infection, normal glucose, calcium, biochemistry
13 Neonatal encephalopathy with seizures Differential Diagnosis Investigations
14 Neonatal encephalopathy with seizures Normal CSF (including glycine) Normal ammonia, lactate Normal amino acids Normal organic acids MRI
15
16 Neonatal encephalopathy with seizures
17 Neonatal encephalopathy with seizures - Laboratory investigations Elevated plasma very long chain fatty acids Elevated bile acid intermediates Mutation in PEX1 gene (7q21).
18 Peroxisomal disorders presenting in neonates Zellweger s disease Neonatal adrenoleucodystrophy Rhizomelic chondrodysplasia punctata
19 Neonatal metabolic encephalopathy: causes Amino acid disorders Organic acid disorders Mitochondrial disorders Peroxisomal disorders Lysosomal enzymes Purine and pyrimidine disorders Metal metabolism disorders Carbohydrate disorders Vitamin metabolism disorders Transport defects Leukodystrophies
20 Neonatal encephalopathy with seizures - clinical clues Deterioration after a normal interval Metabolic acidosis, ketosis, odd smell, hypoglycaemia Hyperammonaemia Low plasma urate Retinopathy Hair abnormality Dysmorphic features, skeletal abnormality EEG
21 Neonatal encephalopathy with seizures Basic investigations glucose; LFT s; blood gas Cranial ultrasound EEG MR / (CT) brain Microarray Ammonia, lactate, urate Biotinidase
22 Neonatal encephalopathy with seizures Extended investigations CSF glucose, lactate and amino acids CSF pyridoxal phosphate CSF MTHF Very long chain fatty acids Copper and caeruloplasmin Carnitine Urine and plasma creatine, GAMT Urine and plasma amino acids Urinary sulphite Urinary organic acids Urinary AASA Fibroblast culture; muscle biopsy;
23 Mitochondrial disorders diagnostic clues Metabolic acidosis Elevated plasma and CSF lactate Ophthalmoplegia and ptosis Cardiomyopathy
24 Molybdenum cofactor deficiency Clinical clues: Lens dislocation Urinary sulphite Plasma urate
25 Congenital disorders of glycosylation 18 disorders now recognised CDG1 caused by mutation in the gene encoding phosphomannomutase Neonatal presentation: Hypotonia Nystagmus Ophthalmoplegia Hepatic dysfunction Diagnosis by transferrin electrophoresis
26 Menke s disease X-linked disorder Abnormality of copper metabolism Encephalopathy with seizures and intracerebral haemorrhage Low plasma copper Vasculopathy Bony fragility
27 Leucodystrophy as a cause of neonatal encephalopathy Pelizaeus Merzbacher disease Classic (X-linked) onset weeks from birth Conatal/late onset forms (AR) Hypotonia Nystagmus Head-nodding, stridor Evolving spasticity Proteolipid (PLP) deletion
28 Genetic EIEE
29
30 Early infantile seizures and dementia - Causes Late / delayed presentation of neonatal onset disorders Plus: Tay Sachs Alpers disease Biotinidase deficiency Early infantile Batten s disease
31 Neuronal Ceroid lipofuscinoses (Batten Disease) Group of severe AR conditions Progressive blindness, seizures and neurodegeneration Originally classified as : Infantile (CLN1, PPT1) Late infantile (CLN2, TPP2) Juvenile (CLN3) Adult Now classified on basis of enzyme defect, genetics, pathological features, phenotype
32 Recombinant human tripeptidyl peptidase-1 (TPP1) 24 patients with CLN2 Significant attenuation in rate of decline in motor and language scores
33 Early infantile seizures and dementia - Investigations As for neonatal onset disorders Plus: VEP/ERG Lysosomal enzymes Electron microscopy skin, lymphocytes Mutation analysis CLN1, CLN2, CLN3, CTSD
34 Case example 2
35 Late infantile central motor deficit A girl presents at 1.5 year of age with normal development until 1 year Followed by slowing in motor development And now loss of independent walking
36 Late infantile central motor deficit OFC 75 th centile Gaze-evoked nystagmus in all directions Normal fundi Mild lower facial weakness Hypotonia in trunk and limbs Reflexes present in arms, absent in legs No visceromegaly
37 Late infantile central motor deficit
38 Late infantile central motor deficit Normal lysosomal enzymes Normal ammonia, lactate and amino acids Normal csf lactate, amino acids
39 Late infantile central motor deficit ENMG: Normal nerve conduction velocities Denervation on EMG Visual evoked potentials Abnormal, delayed responses Normal ERG
40 Late infantile central motor deficit Progressive deterioration continues Visual impairment Dysphagia Loss of social interaction What investigation needs to be done?
41 Late infantile central motor deficit Skin biopsy: Mutation in PLA2G6 gene Diagnosis: Infantile neuroaxonal dystrophy
42 Late infantile central motor deficit - Causes Ataxia telangiectasia ( others Leucodystrophies (metachromatic + Infantile neuroaxonal dystrophy Arginase deficiency Late variant gangliosidoses
43 Late infantile central motor deficit - Causes PDH deficiency (x-linked) Mitochondrial cytopathies Rett syndrome CDG CNS tumours Hydrocephalus
44 Late infantile central motor deficit - Clinical clues Recurrent infection Visual impairment Neuropathy Lactic acidosis Disorders of eye movement Stroke-like episodes
45 Leukodystrophies Genetically determined progressive neurological disorders Abnormalities of structure and development of myelin Recognised by their clinical, imaging and pathology characteristic
46 Hereditary white matter disorders Lysosomal disorders Peroxisomal disorders Mitochondrial disorders DNA repair disorders Defects in myelin proteins Amino acidopathies and organic acidopathies Many others, including congenital muscular dystrophy
47 Leukodystrophies in childhood May 1997-November 2014 n=349, 18 diagnoses Developmental Medicine & Child Neurology 11 FEB 2016 DOI: /dmcn
48 Metachromatic leukodystrophy Arylsulfatase A deficiency Late infantile, juvenile and later variants Late infantile Progressive spasticity and ataxia Absent reflexes and optic atrophy Most die before 8 Juvenile Present at 6-10 years Behavioural disorder, dementia, extrapyramidal movements
49 Krabbe s leucodystrophy Early infantile and later presenting variants Galactocerebrosidase deficiency Early infantile Onset in first 6 months progressive spasticity, optic atrophy and peripheral neuropathy Death often by 2.5 years May be misdiagnosed as cerebral palsy
50 X-linked adrenoleukodystrophy
51 Alexander s leukodystrophy Onset from early infancy to later childhood Progressive spasticity, macrocephaly, dementia Characteristic MR scans frontal predominance No known biochemical disorder Some may be familial GFAP gene deletion in 90%
52
53 Canavan s disease Onset before 1 year Spasticity, macrocephaly, optic atrophy Death in mid to late childhood Urinary excretion of N- acetyl aspartate Spongiform appearance of white matter ASPA mutations (aspartoacylase)
54
55 Megalencephalic leukoencephalopathy with subcortical cysts Infantile onset macrocephaly Delayed onset motor deterioration with spasticity and ataxia Preserved cognition Late onset epilepsy Subcortical cysts in anterior and temporal areas + diffuse white matter abnormality MLC1/HEPACAM mutations Improving phenotype (heterozygous)
56
57 Vanishing white matter disease Childhood ataxia with central nervous system hypomyelination Progressive spastic and ataxic disorder Episodes of sudden deterioration may follow minor head injury Relative preservation of cognition Optic atrophy and blindness Diffuse white matter abnormality, progressing to CSF signal Mutations in 5 genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5) account for 90%
58 Investigations for leukodystrophy MR brain scan and MRS ENMG Lysosomal enzymes Early morning fresh urine for metachromatic material Very long chain fatty acids N-acetyl aspartate Plasma and CSF lactate DNA for Mitochondrial, PLP, GFAP
59 PIND study May 1997-Nov children meeting the criteria for PIND. Diagnosis established in 1580 (42%) 193 distinct disorders. 803/1580 (51%) had leukodystrophy or genetic leukoencephalopathy 349 children leukodystrophies 18 diagnoses 454 children with genetic leukoencephalopathies 38 diagnoses Mucopolysaccharidoses (n=100) GM1 and GM2 gangliosidoses (n=91) Mitochondrial disorders (n=50).
60 Progressive intellectual and neurological deterioration cases with definite diagnoses: the six most commonly reported disease groups. Verity C et al. Arch Dis Child 2010;95: Copyright BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.
61 What about next generation sequencing? Gene panels Whole exome sequencing Whole genome sequencing Phenotyping resources: OMIM Genereviews Phenotips Treatable ID
62 Summary Investigate first for commoner, treatable and reversible disorders (infection, epilepsy etc) Establish whether static or progressive Categorise according to age and predominant area of regression Look for diagnostic clues Target investigations
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 informationSummary. Syndromic versus Etiologic. Definitions. Why does it matter? ASD=autism
Summary It is becoming clear that multiple genes with complex interactions underlie autism spectrum (ASD). A small subset of people with ASD, however, actually suffer from rare single-gene Important to
More informationNational Metabolic Biochemistry Network Best Practice Guidelines. The Biochemical Investigation of Fits and Seizures for Inherited Metabolic Disorders
Introduction National Metabolic Biochemistry Network Best Practice Guidelines The Biochemical Investigation of Fits and Seizures for Inherited Metabolic Disorders These guidelines describe the differential
More informationClinical Summaries. CLN1 Disease, infantile onset and others
Clinical Summaries CLN1 Disease, infantile onset and others The gene called CLN1 lies on chromosome 1. CLN1 disease is inherited as an autosomal recessive disorder, which means that both chromosomes carry
More informationSELECTIVE VULNERABILITY (HYPOXIA AND HYPOGLYCEMIA)
DEFICIENCY OF METABOLITE -HYPOXIA AND HYPOGLYCEMIA -HYPOVITAMINOSIS SELECTIVE VULNERABILITY (HYPOXIA AND HYPOGLYCEMIA) -SPECIFIC CELL TYPE NEURONS>OLIGODENDROCYTES>ASTROCYTES -SPECIFIC BRAIN REGION PYRAMIDAL
More informationChildhood epilepsy: the biochemical epilepsies. Dr Colin D Ferrie Consultant Paediatric Neurologist Leeds General Infirmary
Childhood epilepsy: the biochemical epilepsies Dr Colin D Ferrie Consultant Paediatric Neurologist Leeds General Infirmary Definitions Epileptic Seizure Manifestation(s) of epileptic (excessive and/or
More informationDevelopmental delay Poor School Progress. I Smuts Department of Paediatrics
Developmental delay Poor School Progress I Smuts Department of Paediatrics References Normal development: Handbook of Neurology: Paediatric clinical examination guideline How do children present Children
More informationTraining 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 informationCLINICAL 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 informationA CASE OF GIANT AXONAL NEUROPATHY HEMANANTH T SECOND YEAR POST GRADUATE IN PAEDIATRICS INSTITUTE OF SOCIAL PAEDIATRICS GOVERNMENT STANLEY HOSPITAL
A CASE OF GIANT AXONAL NEUROPATHY HEMANANTH T SECOND YEAR POST GRADUATE IN PAEDIATRICS INSTITUTE OF SOCIAL PAEDIATRICS GOVERNMENT STANLEY HOSPITAL CASE HISTORY Nine year old male child Second born Born
More informationNeonatal Hypotonia Guideline Prepared by Dan Birnbaum MD August 27, 2012
Neonatal Hypotonia Guideline Prepared by Dan Birnbaum MD August 27, 2012 Hypotonia: reduced tension or resistance to range of motion Localization can be central (brain), peripheral (spinal cord, nerve,
More informationNeonatal Hypotonia. Encephalopathy acute No encephalopathy. Neurology Chapter of IAP
The floppy infant assumes a frog legged position. On ventral suspension, the baby can not maintain limb posture against gravity and assumes the position of a rag doll. Encephalopathy acute No encephalopathy
More informationNatural History of JNCL and other NCLs
Natural History of JNCL and other NCLs Jonathan W. Mink, MD PhD Departments of Neurology, Neurobiology & Anatomy, Brain & Cognitive Sciences, and Pediatrics University of Rochester Neuronal Ceroid Lipofuscinosis
More informationMovement disorders in childhood: assessment and diagnosis. Lucinda Carr
Movement disorders in childhood: assessment and diagnosis Lucinda Carr Movement disorders in childhood: Assessment Classification Causes Diagnosis Presentation of movement disorders in childhood: Concerns
More informationmyelin in the CNS Multiple axons are oligodendrocyte
Pathologic classification of white matter disorders d Demyelinating - loss of normal myelin autoimmune/inflammatory component Dysmyelinating - loss of chemically abnormal myelin Hypomyelinating - paucity
More informationEvaluation of the Hypotonic Infant and Child
Evaluation of the Hypotonic Infant and Child Basil T. Darras, M.D. Neuromuscular Program Boston Children s Hospital Harvard Medical School Boston, MA, USA Classification and General Clinical Evaluation
More informationNEONATAL MUSCULAR HYPOTONIA
NEONATAL MUSCULAR HYPOTONIA Differential Diagnosis Systemic causes of neonatal hypotonia should be identified rapidly as they are usually transient if treated appropriately. Major differential diagnoses
More informationSCAD and GA-II: Truths and Confusions
SCAD and GA-II: Truths and Confusions Bill Rhead* Medical College of Wisconsin *MD, PhD GA-II Severe GA-II is as bad as: SCAD + MCAD + COMBINED! VLCAD + IVA + GA-I Severe GA-II is always fatal Mild
More informationNutritional 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 informationHereditary disorders of peroxisomal metabolism.
Hereditary disorders of peroxisomal metabolism http://www.cytochemistry.net/cell-biology/perox.jpg Peroxisomes single membrane organelles from less than 100 to more than 1000 per eucaryotic cell more than
More informationTHIAMINE TRANSPORTER TYPE 2 DEFICIENCY
THIAMINE TRANSPORTER TYPE 2 DEFICIENCY WHAT IS THE THIAMINE TRANSPORTER TYPE 2 DEFICIENCY (hthtr2)? The thiamine transporter type 2 deficiency (hthtr2) is a inborn error of thiamine metabolism caused by
More informationPeroxisomal Disorders
Peroxisomal Disorders George Gray Birmingham Childrens Hospital Peroxisomal Disorders Peroxisomes are large single membrane bound organelles that are present in the cytoplasm of all cells. They are formed
More informationREQUISITION FORM NOTE: ALL FORMS MUST BE FILLED OUT COMPLETELY FOR SAMPLE TO BE PROCESSED. Last First Last First
#: DEPARTMENT OF NEUROLOGY COLUMBIA COLLEGE OF PHYSICIANS & SURGEONS Room 4-420 630 West 168th Street, New York, NY 10032 Telephone #: 212-305-3947 Fax#: 212-305-3986 REQUISITION FORM NOTE: ALL FORMS MUST
More informationNON-JEWISH CHILD WITH CANAVAN DISEASE
case report NON-JEWISH CHILD WITH CANAVAN DISEASE Slouková E. 1, Ošlejšková H. 1, Šoukalová J. 2, Masaříková H. 3 1 Department of Paediatric Neurology, Faculty of Medicine, Masaryk University and Faculty
More informationHereditary disorders of peroxisomal metabolism.
Hereditary disorders of peroxisomal metabolism http://www.cytochemistry.net/cell-biology/perox.jpg Peroxisomes single membrane organelles from less than 100 to more than 1000 per eukaryotic cell more than
More informationThe Floppy Baby. Clare Betteridge
The Floppy Baby Clare Betteridge The floppy baby Identification Evaluation Investigation Diagnosis Examples What is a floppy baby? Elbows and knees loosely extended. Head control is usually poor or absent.
More informationvariant led to a premature stop codon p.k316* which resulted in nonsense-mediated mrna decay. Although the exact function of the C19L1 is still
157 Neurological disorders primarily affect and impair the functioning of the brain and/or neurological system. Structural, electrical or metabolic abnormalities in the brain or neurological system can
More informationDysmorphology Guy Besley
Dysmorphology Guy Besley Willink Biochemical Genetics Unit, Manchester Children s s Hospital Dysmorphic presentation Congenital malformation Disorder of embryogenesis Intrauterine insult infection; chromosomal/genetic
More informationWhat does an EEG show?
EEG Video EEG Ambulatory EEG There s a whole lot of Shakin going on Vagus Nerve Stimulators Division of Child Neurology, Developmental Pediatrics and Genetics Intrathecal Baclofen Pumps EEG first used
More informationSyllabus for Training in Inborn Errors of Metabolism for Scientists and Medically Qualified Laboratory Staff
Training Syllabus LABORATORY SYLLABUS Syllabus for Training in Inborn Errors of Metabolism for Scientists and Medically Qualified Laboratory Staff This syllabus is intended as a guide. Whilst the training
More informationNeurology. Access Center 24/7 access for referring physicians (866) 353-KIDS (5437)
Neurology The Neurology practice at Valley Children s provides diagnostic services, medical treatment, and followup care to infants, children, and adolescents who have suspected or confirmed neurological
More informationNewborn 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 informationFatty Acids Synthesis L3
Fatty Acids Synthesis L3 The pathway for fatty acid synthesis occurs in the cytoplasm, whereas, oxidation occurs in the mitochondria. The other major difference is the use of nucleotide co-factors. Oxidation
More informationCase Report Familial Case of Pelizaeus-Merzbacher Disorder Detected by Oligoarray Comparative Genomic Hybridization: Genotype-to-Phenotype Diagnosis
Hindawi Case Reports in Genetics Volume 2017, Article ID 2706098, 4 pages https://doi.org/10.1155/2017/2706098 Case Report Familial Case of Pelizaeus-Merzbacher Disorder Detected by Oligoarray Comparative
More informationWhat s New in Newborn Screening?
What s New in Newborn Screening? Funded by: Illinois Department of Public Health Information on Newborn Screening Newborn screening in Illinois is administered by the Illinois Department of Public Health.
More informationSYLLABUS 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 informationThe University of Arizona Pediatric Residency Program. Primary Goals for Rotation. Neurology
The University of Arizona Pediatric Residency Program Primary Goals for Rotation Neurology 1. GOAL: Understand the role of the pediatrician in preventing neurological diseases, and in counseling and screening
More informationWhat s New in Newborn Screening?
What s New in Newborn Screening? Funded by: Illinois Department of Public Health Information on Newborn Screening Newborn screening in Illinois is mandated and administered by the Illinois Department of
More informationCHRONIC MYELOGENOUS LEUKEMIA
CHRONIC MYELOGENOUS LEUKEMIA SHUFFLING THE GENETIC DECK IN CML 9 9 (q+) 22 Ph (22q-) bcr bcr-abl abl Fusion protein causes cancer GLEEVEC AND BCR-ABL FUSION PROTEIN GENETIC MEDICINE A. Genetic diseases
More informationThe child with hemiplegic cerebral palsy thinking beyond the motor impairment. Dr Paul Eunson Edinburgh
The child with hemiplegic cerebral palsy thinking beyond the motor impairment Dr Paul Eunson Edinburgh Content Coming to a diagnosis The importance of understanding the injury MRI scans Role of epilepsy
More informationDate of commencement: February Principal Investigator Dr. Jayesh J. Sheth CASE RECORD FORM
ICMR-FRIGE-MULTICENTRIC LSDs Project Foundation for Research in Genetics & Endocrinology [FRIGE], FRIGE House, Jodhpur Gam road, Satellite, Ahmedabad-380015 Tel no: 079-26921414, Fax no: 079-26921415 E-mail:
More informationClinical Approach to Diagnosis of Lysosomal Storage Diseases
Clinical Approach to Diagnosis of Lysosomal Storage Diseases M. Rohrbach, MD, PhD FMH Pädiatrie und FMH Medizinische Genetik Abteilung Stoffwechsel Universitätskinderklinik Zürich Lysosomal storage disorders
More informationNYEIS Version 4.3 (ICD) ICD - 10 Codes Available in NYEIS at time of version launch (9/23/2015)
D82.1 Di George's syndrome E63.9 Nutritional deficiency, unspecified E70.21 Tyrosinemia E70.29 Other disorders of tyrosine metabolism E70.30 Albinism, unspecified E70.5 Disorders of tryptophan metabolism
More informationHypotonia Care Pathway Update: Diagnosis Garey Noritz, MD...
Hypotonia Care Pathway Update: Diagnosis Garey Noritz, MD Disclosure Information- AACPDM 72 nd Annual Meeting October 9-13, 2018 Speaker Name: Garey Noritz, MD Disclosure of Relevant Financial Relationships
More informationUrea 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 informationExploding Genetic Knowledge in Developmental Disabilities. Disclosures. The Genetic Principle
Exploding Genetic Knowledge in Developmental Disabilities How to acquire the data and how to make use of it Elliott H. Sherr MD PhD Professor of Neurology & Pediatrics UCSF Disclosures InVitae: clinical
More informationEvolution of Genetic Testing. Joan Pellegrino MD Associate Professor of Pediatrics SUNY Upstate Medical University
Evolution of Genetic Testing Joan Pellegrino MD Associate Professor of Pediatrics SUNY Upstate Medical University Genetic Testing Chromosomal analysis Flourescent in situ hybridization (FISH) Chromosome
More informationMetabolic 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 informationApproach to the Genetic Diagnosis of Neurological Disorders
Approach to the Genetic Diagnosis of Neurological Disorders Dr Wendy Jones MBBS MRCP Great Ormond Street Hospital for Children National Hospital for Neurology and Neurosurgery What is a genetic diagnosis?
More informationSEX-LINKED INHERITANCE. Dr Rasime Kalkan
SEX-LINKED INHERITANCE Dr Rasime Kalkan Human Karyotype Picture of Human Chromosomes 22 Autosomes and 2 Sex Chromosomes Autosomal vs. Sex-Linked Traits can be either: Autosomal: traits (genes) are located
More informationMyelination, Leukodystrophies and Hypomyelinating Disorders. Florian Eichler, M.D. Massachusetts General Hospital Harvard Medical School
Myelination, Leukodystrophies and Hypomyelinating Disorders Florian Eichler, M.D. Massachusetts General Hospital Harvard Medical School Myelin Lipid bilayer enhanced by intrinsic and extrinsic proteins
More informationNeurologic Examination
John W. Engstrom, MD October 16, 2015 Neurologic Examination Overview The Neurologic Examination Neurologic Examination John W. Engstrom, M.D. Dept. of Neurology University of California, San Francisco
More informationINTRODUCTION. 1.
KRABBE DISEASE INTRODUCTION Krabbe disease is a genetic defect that affects the nervous system. It is caused by the shortage (deficiency) of an enzyme called galactosylceramidase. This enzyme deficiency
More informationDiagnostic Approach to Developmental Delay. Dr Kang Ying Qi Consultant Developmental Pediatrician 20 May 2017
Diagnostic Approach to Developmental Delay Dr Kang Ying Qi Consultant Developmental Pediatrician 20 May 2017 What is development? Young Baby Adulthood Wide variation between children Variation between
More informationDocument Details Investigation of Global Developmental Delay
Title Trust Ref No 1977-28087 Local Ref (optional) Main points the document covers Who is the document aimed at? Author Approved by (Committee/Director) Approval Date 14/9/2015 Initial Equality Impact
More informationDisease of Myelin. Reid R. Heffner, MD Distinguished Teaching Professor Emeritus Department of Pathology and Anatomy January 9, 2019
Disease of Myelin Reid R. Heffner, MD Distinguished Teaching Professor Emeritus Department of Pathology and Anatomy January 9, 2019 1 I HAVE NO CONFLICTS OF INTEREST OR DISCLOSURES TO DECLARE. I HAVE NO
More informationLaura Tormoehlen, M.D. Neurology and EM-Toxicology Indiana University
Laura Tormoehlen, M.D. Neurology and EM-Toxicology Indiana University Disclosures! No conflicts of interest to disclose Neuroimaging 101! Plain films! Computed tomography " Angiography " Perfusion! Magnetic
More informationRedefining HIV encephalopathy in children living in SSA
Redefining HIV encephalopathy in children living in SSA Charles RJC Newton Kenya Medical Research Institute/ Wellcome Trust Collaborative Programme, Kilifi, Kenya Epidemiology of HIV in Children living
More informationThe Neurologic Examination. John W. Engstrom, M.D. University of California San Francisco School of Medicine
The Neurologic Examination John W. Engstrom, M.D. University of California San Francisco School of Medicine Overview The Neurologic Examination Mental status demonstration/questions Cranial nerves demonstration/questions
More informationNeuroradiological Imaging Techniques in Pediatric Neurology
Neuroradiological Imaging Techniques in Pediatric Neurology Rajan Patel, MD Director, Pediatric Neuroimaging Assistant Professor, Division of Neuroradiology DISCLOSURE No financial disclosure. LEARNING
More informationMITOCHONDRIAL DISEASE. Amel Karaa, MD Mitochondrial Disease Program Massachusetts General Hospital
MITOCHONDRIAL DISEASE Amel Karaa, MD Mitochondrial Disease Program Massachusetts General Hospital Disclosures & Disclaimers United Mitochondrial Disease Foundation Research Grant North American Mitochondrial
More informationApproach to the Child with Developmental Delay
Approach to the Child with Developmental Delay Arwa Nasir Department of Pediatrics University of Nebraska Medical Center DISCLOSURE DECLARATION Approach to the Child with Developmental Delay Arwa Nasir
More informationProvide specific counseling to parents and patients with neurological disorders, addressing:
Neurology Description: The Pediatric Neurology elective will give the resident the opportunity to learn how to obtain an appropriate history and perform a complete neurologic exam. Four to five half days
More informationMedical Conditions Resulting in High Probability of Developmental Delay and DSCC Screening Information
Jame5. L.Jma5, ~reuiry Medical Conditions Medical Conditions Resulting in High Probability of Developmental Delay and DSCC Screening Information I Not Listed later Children with medical conditions which
More informationIntroduction 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 informationInfantile-onset Alexander disease in a child with long-term follow-up by serial magnetic resonance imaging: a case report
Nishibayashi et al. Journal of Medical Case Reports 2013, 7:194 JOURNAL OF MEDICAL CASE REPORTS CASE REPORT Open Access Infantile-onset Alexander disease in a child with long-term follow-up by serial magnetic
More informationFRAMBU. Resource Centre for Rare Disorders
FRAMBU Resource Centre for Rare Disorders Frambu Resource Centre for Rare Disorders is one of nine centres working with rare disorders in Norway. All nine centres are part of the Norwegian National Advisory
More informationEPILEPSY. Elaine Wirrell
EPILEPSY Elaine Wirrell Seizures are amongst the most common of neurological disorders in the pediatric age range. The incidence of new-onset epilepsy in children is approximately 40 per 100,000 per year
More informationSubspecialty Rotation: Child Neurology at SUNY (KCHC and UHB) Residents: Pediatric residents at the PL1, PL2, PL3 level
Subspecialty Rotation: Child Neurology at SUNY (KCHC and UHB) Residents: Pediatric residents at the PL1, PL2, PL3 level Prerequisites: Any prior pediatric rotations and experience Primary Goals for this
More informationClinical Approach to Leukoencephalopathies
29 Deborah L. Renaud, M.D. 1 1 Departments of Neurology and Pediatrics, Mayo Clinic, Rochester, Minnesota Semin Neurol 2012;32:29 33. Address for correspondence and reprint requests Deborah L. Renaud,
More informationTRANSAMINATION 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 informationCentral Nervous System
Central Nervous System Developmental delay Loss of milestones Intellectual disability Dementia Seizures Neuropsychiatric disturbances Cerebral palsy Migraines Stroke and stroke-like episodes Movement disorders:
More informationCSF Investigations in patients with seizures. Dr Simon Olpin Sheffield Children s Hospital
CSF Investigations in patients with seizures Dr Simon Olpin Sheffield Children s Hospital Background Epileptic seizures common feature in many inherited metabolic disorders particularly those involving
More informationpanel tests assessing multiple genes at the same time for the diagnosis of one or more related disorders
NGS tests panel tests assessing multiple genes at the same time for the diagnosis of one or more related disorders UKGTN website lists 13 laboratories offering a total of 56 panel test UKGTN listed panel
More informationModule : 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 informationTOXIC AND NUTRITIONAL DISORDER MODULE
TOXIC AND NUTRITIONAL DISORDER MODULE Objectives: For each of the following entities the student should be able to: 1. Describe the etiology/pathogenesis and/or pathophysiology, gross and microscopic morphology
More informationInborn errors of metabolism causing epilepsy
DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY REVIEW Inborn errors of metabolism causing epilepsy SHAMIMA RAHMAN EMMA J FOOTITT SOPHIA VARADKAR PETER T CLAYTON Clinical and Molecular Genetics and Neurosciences
More informationCase Reports. Neonatal Seizure: A Rare Aetiology Easily Missed by Routine Metabolic Screening LY SIU, L KWONG, SN WONG, NS KWONG
HK J Paediatr (new series) 2009;14:37-41 Case Reports Neonatal Seizure: A Rare Aetiology Easily Missed by Routine Metabolic Screening LY SIU, L KWONG, SN WONG, NS KWONG Abstract Key words We present the
More informationChild Neurology Elective PL1 Rotation
PL1 Rotation The neurology elective is available to first year residents in either a 2 or 4 week block rotation. The experience will include performing inpatient consultations, attending outpatient clinics
More informationThe Neurology of HIV Infection. Carolyn Barley Britton, MD, MS Associate Professor of Clinical Neurology Columbia University
The Neurology of HIV Infection Carolyn Barley Britton, MD, MS Associate Professor of Clinical Neurology Columbia University HIV/AIDS Epidemiology World-wide pandemic, 40 million affected U.S.- Disproportionate
More informationINBORN 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 informationScholars Journal of Medical Case Reports
DOI: 10.21276/sjmcr.2016.4.6.27 Scholars Journal of Medical Case Reports Sch J Med Case Rep 2016; 4(6):448-452 Scholars Academic and Scientific Publishers (SAS Publishers) (An International Publisher for
More informationPostnatal Exome Sequencing
Postnatal Exome Sequencing Ata Bushehri, MD, PhD candidate Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Genetic Counseling Overview Pattern of Inheritance
More informationUCL INSTITUTE OF NEUROLOGY DCEE. HNF1B and the brain
UCL INSTITUTE OF NEUROLOGY DCEE HNF1B and the brain Sanjay Sisodiya Department of Clinical and Experimental Epilepsy UCL Institute of Neurology National Hospital for Neurology and Neurosurgery, Queen Square
More informationCLN2 disease progresses rapidly. Diagnose earlier to treat sooner.
Brineura (cerliponase alfa) injection for intraventricular use is indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid
More informationVascular Disorders. Nervous System Disorders (Part B-1) Module 8 -Chapter 14. Cerebrovascular disease S/S 1/9/2013
Nervous System Disorders (Part B-1) Module 8 -Chapter 14 Overview ACUTE NEUROLOGIC DISORDERS Vascular Disorders Infections/Inflammation/Toxins Metabolic, Endocrinologic, Nutritional, Toxic Neoplastic Traumatic
More informationClinical Cell Biology Organelles in Health and Disease
Department of Ophthalmology University of Kiel, University Medical Center Director: Prof. Dr. Johann Roider Clinical Cell Biology Organelles in Health and Disease Prof. Dr. Alexa Klettner Clinical cell
More informationNEONATAL 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 informationManagement of Neonatal Seizures
Management of Neonatal Seizures Manal E. Moustafa Assistant Professor of Pediatric Neurology and Epilepsy Children s Healthcare of Atlanta/Emory University Disclosures I have none! 1 Objectives Recognition
More informationTHE VEGETATIVE STATE IN INFANCY AND CHILDHOOD
THE VEGETATIVE STATE IN INFANCY AND CHILDHOOD Stephen Ashwal MD, Professor of Pediatrics and Neurology, Chief, Division of Child Neurology, Department of Pediatrics, Loma Linda University School of Medicine,
More informationThe Role of Organic Acids in the Diagnosis of Peroxisomal Biogenesis Disorders
The Role of Organic Acids in the Diagnosis of Peroxisomal Biogenesis Disorders Catherine Dibden Northern General Hospital Sheffield Children s Hospital Peroxisomes Small sub-cellular organelles Present
More informationEpilepsy in the Primary School Aged Child
Epilepsy in Primary School Aged Child Deepak Gill Department of Neurology and Neurosurgery The Children s Hospital at Westmead CHERI Research Forum 15 July 2005 Overview The School Age Child and Epilepsy
More informationMuscle Metabolism. Dr. Nabil Bashir
Muscle Metabolism Dr. Nabil Bashir Learning objectives Understand how skeletal muscles derive energy at rest, moderate exercise, and strong exercise. Recognize the difference between aerobic and anaerobic
More informationData Collection Worksheet
Data Collection Worksheet To maximize consistency, the authors of the scale state that it is essential that clinicians adhere to the scale instructions. They also advise that the scales be administrated
More informationBROADENING YOUR PATIENT S OPTIONS FOR GENETIC CARRIER SCREENING.
BROADENING YOUR PATIENT S OPTIONS FOR GENETIC CARRIER SCREENING. The Inheritest SM Carrier Screen provides relevant genetic screening for many inherited diseases found throughout the pan-ethnic US population.
More informationNo relevant disclosures
No relevant disclosures - Epileptic Encephalopathy (EE): Epileptic activity itself contributes to cognitive and behavioural impairments - Developmental and Epileptic Encephalopathy (DEE): Impairments occur
More informationThere are several types of epilepsy. Each of them have different causes, symptoms and treatment.
1 EPILEPSY Epilepsy is a group of neurological diseases where the nerve cell activity in the brain is disrupted, causing seizures of unusual sensations, behavior and sometimes loss of consciousness. Epileptic
More informationD evelopmental disabilities occur in approximately
1128 REVIEW Developmental delay: when to suspect and how to investigate for an inborn error of metabolism M A Cleary, A Green... The purpose of this review is to provide a practical guideline on the suspicion
More informationHematopoietic Stem Cell Transplantation for Adrenoleukodystrophy
Hematopoietic Stem Cell Transplantation for Adrenoleukodystrophy 2011 NHLBI Pediatric Workshop Sept. 14, 2011 Paul Orchard, M.D. Division of Pediatric Blood and Marrow Transplant University of Minnesota
More informationSredišnja medicinska knjižnica
Središnja medicinska knjižnica Maradin, M., Fumić, K., Hansikova, H., Tesarova, M., Wenchich, L., Dorner, S., Sarnavka, V., Zeman, J., Barić, I. (2006) Fumaric aciduria: Mild phenotype in a 8-year-old
More information