Evening Case studies, Tuesday April 30, Vijay L. Grey McMaster University
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1 Evening Case studies, Tuesday April 30, 2013 Vijay L. Grey McMaster University
2 Case 1 Gus Diaz was born to a 28-year-old gravida I mom who had evidence of gestational diabetes. It was managed with attention to diet and exercise. The baby's weight, head circumference, and length were all within normal.
3 Case 1 The baby appeared jittery at 2h and Mom tried to nurse. A POCT glucose was measured and was 41mg/dL (2.3mmol/L). The sample was sent to the lab for confirmation and the value was 39mg/dL (2.1mmol/L). The baby was given dextrose and no longer was jittery. POCT glucose was 63mg/dL (3.5mmol/L). The baby seemed to nurse successfully throughout the day and no other symptoms were recorded.
4 Question Why was the lab confirmation necessary? Comment on the accuracy/precision of POCT glucose meters
5 Case 1 The next day again the baby was jittery and a POCT glucose was done. It was 49mg/dL(2.7mmol/L) and the lab result was 30mg/dL (1.7mmol/L). The baby was given dextrose again. Throughout the day the baby nursed and the glucose was variable at about 47mg/dL (2.6 mmol/l) pre-prandial
6 Question Recurrent hypoglycemia? Other tests?
7 Risk Factors for hypoglycemia Maternal metabolism IV glucose Maternal diabetes Other factors Intra uterine growth retardation Preterm Hyper-insulism Endocrine disorder Inherited metabolic disorder
8 Persistent Hypoglycemia Plasma glucose <36mg/dL (2.0mmol/L) Inadequate glucose supply Increased glucose utilization
9 Other results Urine ketones absent Β-hydroxybutyrate < 1.04mg/dL (100μmol/L) FFA ordered but result not available
10 Case 1 On day 2 a plasma insulin was ordered and the result was 27μU/mL RI= 3-19μU/mL FFA result = 0.2mmol/L ( mmol/L)
11 Persistent hypoglycemia Inadequate glucose supply ketonuria Increased glucose utilization No ketonuria Low FFA Urine reducing substances Plasma K and Na Acid-base status Insulin >10U/L Β-hydroxybutyrate <1.04mg/dL (100μmol/L) C-peptide Investigate for endocrine and metabolic causes Investigate for hyperinsulism
12 Hyperinsulism Acquired Maternal diabetes Gestational diabetes Insulinoma SGA Genetic GK deficiency Beckwith syndrome
13 Question How is gestational diabetes diagnosed?
14 The diagnosis of GDM is made when Fasting glucose 92mg/dL (5.1mmol/L) 1h OGTT 180mg/dL (10.0mmol/L) 2h OGTT 153 mg/dl (8.5 mmol/l)
15 Case 2 2y old African American with recurrent wheezing. Of note the patient has not gained weight in the past six months and is on the low end of growth chart Mother says patient eats well and has 2-3 loose stools a day.
16 History Birth History 37 wk gestation Normal pregnancy Birth weight = 4.1kg and height=53.5cm(80%ile) Breast fed
17 Question What are causes of failure to thrive? Inadequate calories Chronic disease e.g., malabsorption, renal disease, lung disease Childhood cancer Hypothyroidism Diabetes Disorders of GH-IGF axis
18 History He has had frequent colds and ear infections At last checkup 6 months ago his growth seemed to have slowed, but otherwise appeared healthy.
19 Question What lab tests would you order? Celiac testing Sweat Chloride TSH and ft 4 glucose
20 Lab Results Sweat Chloride = 70mmol/L All other results unremarkable Diagnosis CF Frequency of CF carriers In Caucasians 1 in 25 in African Americans 1 in 65
21 CF CFTR gene was identified 20y ago and the 1800 mutations make the relation between genotype and phenotype challenging since all mutations may not be disease causing
22 CF CF is caused by loss of function in the CFTR gene Diagnosis is based on clinical symptoms, +ve sweat chloride And CF causing mutations One particular mutation F508 occurs in ~70% of CFTR genes from CF patients
23 Genotype and Phenotype The F508 mutation appears to be associated with the classic form of CF: 1) high level of Cl- in sweat 2) pancreatic insufficiency However, pulmonary disease -- the life-limiting feature of CF -- appears to be variable in those with this common mutation. This reflects the phenotypic variation of the F508 mutation.
24 Genotype and Phenotype Although F508 is the most common CF mutation, its frequency varies among populations: a. Northern Europeans % of CF mutations b. Southern Europeans % of CF mutations c. Ashkenazi & African-American lower rates
25 Categories of CFTR mutations
26 Classes Class I Failure to synthesize full length protein Class I defect is characterize by x (stop signal) in gene (or nonsense alleles) i.e.: 1. G542X 2. R553X 3. W1282X Class II Improper folding/ trafficking to cell membrane (misfolded) i.e.: 1. ΔF N1303K
27 Classes Class III Defect in regulation impairs opening of channel (gating defect) i.e: 1. G551D 2. G551S Class IV Defect in channel impairs ion transport (conductance defect) i.e.: 1. R117H 2. R334W 3. R347P
28 Classes Class V Splicing error causes variable synthesis of protein (CFTR) i.e kb C T 2. A455E Class VI Protein truncation causes increased cell surface turnover i.e deletion TC (defective CFTR stability at the cell surface)
29 Other Questions Was NBS done? Results were indeterminate Sweat Chloride was 20 meq/l (mmol/l) and 33 meq/l (mmol/l) on 2 separate occasions IRT and 0 CF mutation (panel screened for 20 common mutations)
30 Sweat testing in Newborns Infants with intermediate sweat chloride values and no or 1 CF-causing mutation cannot be diagnosed definitively. Sweat testing should be repeated 2-6months later
31 Case 2 Patients may be PS at birth but become PI within 1-2 y What lab tests should be done at this time? Malabsorption (fecal fat) Serum Lipase Nutritional status assessed.
32 Case 3-Billy Jones Baby Boy, 39 3/7 weeks gestation, birth weight 3350 grams, Father is from Scotland and Mother is from the Middle East, Mother is blood group O+. Spontaneous vaginal delivery at h on March 1/08. No complications. Baby is well with no concerns. Mother is breastfeeding.
33 Case 3-Billy Jones At 24 h of age the nurse noted that the baby appeared clinically jaundiced The TSB is ordered and it is 10mg/dL (170 μmol/l) During the night a nurse performed a TCB measurement and it was 13mg/dL (222 μmol/l)
34
35 Case 3-Billy Jones Since the baby has plotted in the HIGH RISK ZONE and mother is blood group O+, a Coombs test is required. The Coombs test is negative.
36 Indication for Coombs Testing
37 The TSB is repeated the next morning and the result on Mar 2/08 at at 34 hours of age is 15mg/dL (265 μmol/l). Intensive phototherapy is initiated. The physician phoned the laboratory to enquire about G-6PD testing.
38 Phototherapy Nomogram (
39 Question Why G6PD? Screen at-risk infants African American, South-east Asian, Greek, Italian, Sephardic Jews, Chinese
40 Copyright 1999 American Academy of Pediatrics Incidence of hyperbilirubinemia Kaplan, M. et al. Pediatrics 1999;104:68-74
41 Case pm Thursday Dec 24 th Patient with Na- 199 meq/l (mmol/l) CL- 172 meq/l (mmol/l) Other results K normal, chloride elevated
42 Case 4 A call to the ward and technologist was informed that baby was started on TPN yesterday. Frequent measurements will be required
43 Case 4-Question Should further values be telephoned as critical? The ward has a printer and results are also electronic
44 Case 4 Time Na K Cl CO meq/l (mmol/l) meq/l (mmol/l) meq/l (mmol/l) meq/l (mmol/l) 28/3 1pm pm pm pm pm /3 5am am pm /3 8am pm
45 Case 4 In pediatric hospitals, hypernatremia not uncommon due to improperly reconstituted formula. Frequent evaluations may be required as adjustments are made to a stable required level.
46 Case 5 History & Physical: 14 year-old, Hispanic female, presented with abdominal pain, dizziness and headache. She reported a few weeks of polyuria, nocturia, increased thirst and increased appetite. On physical exam, she was 5 4, 92 lbs, and illappearing.
47 CASE 5 Principle LaboratoryFindings: TestResult ph 7.08 ( ) pco 2 24 (41 54 mm/hg) HCO3 7 (18-26 meq/l) Glucose 932 (51.7) ( mg/dl[ mm])
48 Type of Acidosis? Question
49 CASE 5 Principle LaboratoryFindings: TestResult ph 7.08 ( ) pco 2 24 (41 54 mm/hg) HCO3 7 (18-26 mmol/l) Anion Gap 32 (5-14) Glucose 932 (51.7) ( mg/dl[ mm])
50 Question Metabolic Acidosis with Anion Gap Other tests?
51 Glucose Β-OHbutyrate (46.7) mg/dL (3-5.9mmol/L) HbA 1c % 0-4mg/dL
52 Diagnosis New Onset Diabetic Ketoacidosis (DKA)
53 Most common cause of a high anion gap metabolic acidosis -OH-butyrate Ketone - ~75% of ketones during ketosis Best ketone for monitoring resolution of ketosis Urine ketones measure acetoacetate
54 Diabetes diagnosis A1C > 6.5% or FPG > 126 mg/dl (7.0 mmol/l) or 2 hr glucose > 200 mg/dl (11.1 mmol/l) during 75 g - OGTT
55 Case 6 A 10 year old boy had some routine electrolytes drawn. Na meq/l (mmol/l) K 13.0 H meq/l (mmol/l) Cl meq/l (mmol/l) Ca <0.125 (0.05) *L mg/d( mmol/l) Albumin g/dl
56 Case 6 The lab phones the ward and asks for another sample Na meq/l (mmol/l) K meq/l (mmol/l) Cl meq/l (mmol/l) Ca 9.0 (2.25 ) mg/d( mmol/l) Albumin g/dl Explain
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