Inborn Errors: Hypoglycemia & Disorders of Fat Utilization Flashcards
1
Q
Major glycogen storage diseases
A
- G6Phosphatase Deficiency
- Debranching enzyme deficiency
- Branching enzyme deficiency
- Phosphorylase deficiency
- Phosphorylase kinase deficiency
2
Q
Biochemical mechanisms of G6Phosphatase Deficiency
A
- Profound defect in hepatic glucose production during fasting
- Liver is dramatically enlarged with glycogen
- Lactic acidosis
- Increased fatty acid synthesis → hypertriglyceridemia
- Elevated ketones from fat oxidation
3
Q
Clinical presenation of G6P deficiency
A
- Infants present within 1st year of life
- Increased risk of infections
- Growth retardation
- Improves in adulthood
4
Q
Characteristics of debranching enzyme deficiency
A
- Present later in early life with moderate hypoglycemia, hepatomegaly, delayed growth and short stature
- Increased ketones from fat oxidation
- Can affect liver + muscles or just liver
- Improves clinically by adulthood
5
Q
Characteristics of branching enzyme deficiency
A
- Abnormal glycogen accumulates in liver and skeletal muscle
- Tissue damage most prominent symptoms
- Also get hepatomegaly and weakness due to myopathy, cardiomyopathy
- Severe liver injury → cirrhosis + death < 6 years old
6
Q
Characteristics of phosphorylase deficiency
A
- Mild phenotype
- Hepatomegaly + mild muscle weakness during exercise
- Hypoglycemia mild 12-15 hours after meal
- Avoid long fasting
7
Q
Characteristics of phosphorylase kinase deficiency
A
- More severe
- Liver fibrosis
- Moderate to severe hypoglycemia
- Can progress to cirrhosis
8
Q
Cause of Hereditary fructose intolerance
A
- Aldolase B deficiency
- causes build up of fructose-1-phosphate which inhibits glycolysis & gluconeogenesis
9
Q
Clinical features of hereditary fructose intolerance
A
- Occurs when fruit is introduced into diet
- Hypoglycemia
- N/V
- Palor
- Coma
- Progressive Liver and kidney failure → elevated LFTs
- Symptoms worsen with high fructose
- Treat with fructose restriction
10
Q
Cause of galactosemia
A
- Galactosemia occurs when there is a deficiency in the enzyme that produces UDP galactose.
- The enzyme is galactose-1-phosphate uridyltransferase (GALT)
11
Q
Clinical presentation of Galactosemia
A
- Occurs when milk introduced into diet
- Buildup of galactose and its metabolites → liver damage and jaundice
- Coagulation disturbances
- Cataract formation
- N/V after ingestion of milk
- Neuro problems including ataxia, tremor, speech impairment
- Treatment is dietary lactose restriction
12
Q
Common disorders of fat metabolism
A
- CoA Dehydrogenase deficiency (MCAD)Medium chain acyl
- Very long chain acyl CoA dehydrogenase deficiency (VLCAD)
- CPT-1 deficiency
13
Q
Clinical features of CoA Dehydrogenase deficiency (MCAD)Medium chain acyl
A
- Can’t β oxidize medium chain fatty acids
- Increased peripheral glucose utilization
- Gluconeogenic precursors end up as organic acids in urine
- Failure to produce ketone bodies
- Presents in infancy → childhood after prolonged fasting, esp during viral illness
- Low insulin
- High medium chain acyl carnitines
14
Q
Clinical features of Very long chain acyl CoA dehydrogenase deficiency (VLCAD)
A
- Similar to MCAD but milder and appears later in life
- Muscle soreness and rhabdomyolysis after exercise
15
Q
Clinical features of CPT-1 deficiency
A
- CPT1 carries fatty acids into mitochondria → defect in fat oxidation
- Fasting hypoglycemia
- Present in infancy after illness
- Increased serum carnitine, low levels of acyl carnitines
- Elevated ammonia
- Treatment = constant carbs to prevent hypoglycemia
