Metabolics Flashcards
List 5 clinical features that are suspicious for IEM in a severely ill neonate
Well at birth Lethargy Poor feeding Seizure Vomiting Hypotonia Liver dysfunction AG-acidosis Hypoketotic hypoglycemia Unusual odor
List 4 clinical presentations of IEM in an older child
Developmental regression Seizures Encephalopathy Myopathy Recurrent vomiting Cardiomyopathy Unusual odor (especially during illness)
What initial labs do you order in suspected IEM
First tier: CBC, diff VBG Lytes Glucose Ammonium Lactate Urine ketones Urine reducing substances
Second tier: Urine OA Plasma AA Plasma acylcarnitine Plasma free carnitine CSF AA, NT, lactate
As a rule of thumb, hyperammonemia with no acidosis is suggestive of which IEM?
Urea cycle defect
As a rule of thumb, hyperammonemia, AG acidosis, ketosis, hypoglycemia is suggestive of which IEM?
Organic acidemias (e.g. propionic acidemia)
As a rule of thumb, AG-acidosis and elevated lactate is suggestive of which IEMs?
- Disorders of glycogenolysis (e.g. GSD I)
- Disorders of pyruvate metabolism (e.g. pyruvate dehydrogenase deficiency)
- Disorders of gluconeogenesis (e.g. fructose 1, 6 bisphosphatase, pyruvate carboxlase deficiency, PEPCK)
- Mitochondrial disorders
What IEMs are associated with cytpenias?
GSD Type I-neutropenia
Propionic acidemia-neutropenia, thrombocytopenia
MMA
Describe the pathophysiology of glycogen storage diseases
Defects in glycogen metabolism cause:
i) Hypoglycemia
ii) Ketosis (because fat is being broken down instead of glucose)
iii) Accumulation of glycogen in tissues
List the most common glycogen storage diseases that primarily affect the liver
Type Ia/Ib (Von GIerke Dz): Glucose-6-phosphatase deficiency
Type III: Debrancher deficiency (involves liver and muscle)
Type IX: Liver phosphorylase kinase deficiency
List the most common glycogen storage diseases that primarily affect the muscle
o Type II (Pompe): Lysosomal acid α-glucosidase deficiency
Type V: Myophosphorylase deficiency (McArdle disease)
How do liver glycogen storage diseases typically present?
Fasting hypoglycemia
Ketosis
Hepatomegaly
Hypotonia
How do muscle glycogen storage diseases typically present?
Symptoms with exercise
Muscle pain, cramps
Myoglobinuria
How does GSD Ia/b (von Gierke) present?
Early infancy Hepatomegaly Hypoglycemia Lactic acidosis Hypotonia Mild DD FTT Recurrent infections (Neutropenia) Bleeding diathesis (platelet dysfn) Renal-large kidneys, FSGS, HTN
List laboratory features consistent with GSD Ia/b
Hypoglycemia Lactic acidosis Ketoacidosis Hyperlipidemia Neutropenia Hyperuricemia
How do you diagnose GSD Ia/b?
Molecular DNA testing
If negative, muscle/liver biopsy
Treatment of GSD Ia/b
- Keep blood glucose normal:
- Frequent administration of uncooked cornstarch
- Add maltodextrin to breastmilk - GCSF for neutropenia
- Allopurinol for hyperuricemia
- Liver transplant
List 3 clinical features of Pompe disease (GSD II)
Cardiomyopathy
Severe hypotonia
Macroglossia
Hepatomegaly (d/t heart failure)
How do you diagnose Pompe disease?
↓ acid maltase activity in leukocytes or fibroblasts can
Muscle biopsy not required
What are the characteristic ECG findings in Pompe disease?
Short PR BV hypertrophy (high voltage QRS in all leads)
Treatment for Pompe disease
Enzyme replacement therapy
High protein, low carbohydrate diet
OT/PT
What enzyme is deficient in classic galactosemia?
GALT (galactose-1-phosphate uridyl transferase)
Describe the pathophysiology of galactosemia
Accumulation of galactose because of GALT deficiency
Galactose converted to galactitol=TOXIC
Injury to kidney, liver and brain
How and when does classic galactosemia typically present?
First few days of life after receiving BF/formula containing lactose
Conjugated hyperbilirubinemia Vomiting Hypoglycemia Cataracts Hepatomegaly-->Liver failure Mental retardation
What infection are neonates with galactosemia at increased risk of?
E. Coli sepsis