Inborn Errors: Hypoglycemia & Disorders of Fat Utilization Flashcards Preview

DEMS: Unit II > Inborn Errors: Hypoglycemia & Disorders of Fat Utilization > Flashcards

Flashcards in Inborn Errors: Hypoglycemia & Disorders of Fat Utilization Deck (18)
Loading flashcards...

Major glycogen storage diseases

  • G6Phosphatase Deficiency
  • Debranching enzyme deficiency
  • Branching enzyme deficiency
  • Phosphorylase deficiency
  • Phosphorylase kinase deficiency


Biochemical mechanisms of G6Phosphatase Deficiency

  • 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


Clinical presenation of G6P deficiency

  • Infants present within 1st year of life
  • Increased risk of infections
  • Growth retardation
  • Improves in adulthood


Characteristics of debranching enzyme deficiency

  • 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


Characteristics of branching enzyme deficiency

  • 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


Characteristics of phosphorylase deficiency

  • Mild phenotype
  • Hepatomegaly + mild muscle weakness during exercise
  • Hypoglycemia mild 12-15 hours after meal
  • Avoid long fasting


Characteristics of phosphorylase kinase deficiency

  • More severe
  • Liver fibrosis
  • Moderate to severe hypoglycemia
  • Can progress to cirrhosis


Cause of Hereditary fructose intolerance

  • Aldolase B deficiency
  • causes build up of fructose-1-phosphate which inhibits glycolysis & gluconeogenesis


Clinical features of hereditary fructose intolerance

  • 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


Cause of galactosemia

  • Galactosemia occurs when there is a deficiency in the enzyme that produces UDP galactose.
  • The enzyme is galactose-1-phosphate uridyltransferase (GALT)


Clinical presentation of Galactosemia 

  • 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


Common disorders of fat metabolism

  • CoA Dehydrogenase deficiency (MCAD)Medium chain acyl
  • Very long chain acyl CoA dehydrogenase deficiency (VLCAD)
  • CPT-1 deficiency


Clinical features of CoA Dehydrogenase deficiency (MCAD)Medium chain acyl

  • 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


Clinical features of Very long chain acyl CoA dehydrogenase deficiency (VLCAD)


  • Similar to MCAD but milder and appears later in life
  • Muscle soreness and rhabdomyolysis after exercise


Clinical features of CPT-1 deficiency

  • 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


Common non-inborn causes of hypoglycemia

Large for gestational age newborn → high serum insulin + hypoglycemia post birth

Ketogenic hypoglycemia → elevated ketones, reduced muscle protein

Insulinoma → Adults as part of MEN-1. Surgical removal

Cortisol deficiency → Adrenal/pituitary gland failure.  Low insulin + cortisol when hypoglycemic.

Insulin overdose → child abuse, homicide.  No extra C-peptide present

Sulfonylurea ingestion → increased insulin, C-peptide, screen + for sulfonylurea

Ethanol ingestion → inhibits gluconeogenesis.  Happens in alcoholics who drink a lot without eating carbs

Too little lean and fat mass


Key blood tests in hypoglycemia dx

  • Confirmatory glucose concentration
  • Insulin
  • cortisol, growth hormone
  • Ketones (acetoacetate - urine/β-OH butyrate - blood)
  • Lactate and pyruvate in suspected glycogen storage disease (Sufonylurea screen)
  • C-peptide


Key Urine tests in hypoglycemia


Urine reducing substances (“non-glucose”) in newborns suspected of galactosemia