Congenital Metabolic Disorders Flashcards Preview

USMLE Step 1 > Congenital Metabolic Disorders > Flashcards

Flashcards in Congenital Metabolic Disorders Deck (22)
Loading flashcards...

Pyruvate dehydrogenase deficiency

Findings: neurologic defects Enzyme deficient: Pyruvate Dehydrogenase Accumulated substrate: Pyruvate, Alanine Treatment: increase intake of ketogenic nutrients such as fat or lysine and leucine


Glucose 6-phosphate dehydrogenase deficiency

Findings: Hemolytic anemia, Heinz bodies (oxidized hemoglobin precipitated within RBCs), Bite cells (from phagocytic removal of Heinz bodies by splenic macrophages) Enzyme Deficient: Glucose-6-phosphate dehydrogenase Deficient cellular molecule: NADPH Precipitating factors: ingestion of fava beans, sulfonamides, primaquine, antituberculosis drugs, infection (inflammatory response produces free radicals, cause oxidative damage to RBCs) Inheritance: XR; most common human enzyme deficiency; more prevalent among blacks, increased malarial resistance


Essential fructosuria

Findings: fructose in blood and urine Enzyme Deficient: Fructokinase Inheritance: AR


Fructose intolerance

Findings: Hypoglycemia, jaundice, cirrhosis, vomiting Enzyme Deficient: Aldolase B Accumulated substrate: Fructose-1-phosphate Inheritance: AR Phosphorylated fructose builds up in cells causing inhibition of glycogenolysis and gluconeogenesis Treatment: decrease intake of both fructose and sucrose


Galactokinase deficiency

Findings: galactose appears in blood and urine, infantile cataracts; failure of child to track objects or to develop a social smile Enzyme Deficient: Galactokinase Accumulated substrate: Galactitol Inheritance: AR


Classic galactosemia

Findings: Failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation Enzyme Deficient: Galactose-1-phosphate uridyltransferase Accumulated substrate: Galactitol Inheritance: AR Treatment: exclude galactose and lactose from diet


Lactase deficiency

Findings: bloating, cramps, osmotic diarrhea; may follow gastroenteritis Enzyme Deficient: Lactase Treatment: avoid dary products or add lactase pills to diet


Ornithine transcarbamoylase (OTC) deficiency

Findings: Orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia (tremor, vomiting, cerebral edema, blurring of vision) Enzyme Deficient: OTC Accumulated Substrate: ammonia Inheritance: XR Often evident in the first few days of life, may present later.



Findings: mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor Enzyme Deficient: phenylalanine hydroxylase OR tetrahydrobiopterin cofactor Inheritance: AR Tyrosine becomes essential. Maternal PKU with lack of dietary therapy results in microcephaly, mental retardation, growth retardation, and congenital heart defects for the infant.


Leber's hereditary optic neuropathy

Findings: progressive loss of central vision and eventual blindness due to degeneration of the optic nerve Enzyme Defect: NADH dehydrogenase (complex 1 of ETC) Inheritance: mitochondrial (maternal) Most common onset in the third decade.


Kearns-Sayre syndrome

Findings: degeneration of retinal pigments, ophthalmoplegia, pain in the eyes, and cardiac conduction defects, which may because death. Muscle biopsy reveals ragged red fibers marked by an irregular contour and structurally abnormal mitochondria that stain red. Inheritance: mitochondrial (maternal) Onset occurs before age 20 years.


MELAS syndrome

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes


MERRF syndrome

Myoclonus epilepsy with ragged red fibers


Von Gierke's disease

Findings: Severe fasting hypoglycemia, ketosis, hyperlipidemia, lactic acidosis, enlarged liver and kidneys (hepatorenomegaly) Enzyme Deficient: Glucose 6-phosphatase (liver and kidney) Inheritance: AR


Pompe's disease

Findings: Infant and Adult forms: Infant: mental retardation, hypotonia, cardiomegaly leading to death by age 2 Adult: gradual skeletal myopathy Enzyme Deficient: alpha-1,4-Glucosidase (lysosomes) Inheritance: AR


Cori's disease

Findings: Mild hypoglycemia, hepatomegaly; decrease in free glucose after epinephrine challenge Enzyme Deficient: Debranching enzyme (muscle and liver), amylo-alpha-1,6-glucosidase Inheritance: AR Abnormal glycogen structure: many short-branched chains


Andersen's disease

Findings: Hepatosplenomegaly, cirrhosis, liver failure leading to death by age 2 Enzyme Deficient: Branching enzyme (liver and spleen), glucosyl 4,6-transferase Inheritance: AR Abnormal glycogen structure: few long chains with very few branches


McArdle's disease

Findings: Muscle cramping, fatigue, and myoglobinuria with strenuous exercise; no increase in lactic acid after exercise Enzyme Deficient: Muscle glycogen phosphorylase Inheritance: AR



Findings: Dark connective tissue, brown pigmented sclera, urine turns black on prolonged exposure to air. Possible debilitating arthralgias. Enzyme Deficient: homogentisic acid oxidase Inheritance: AR Mostly a benign disease.


Cystinuria: mechanism, tx

  • defect in renal + intestinal transporter of COLA:
    • Cysteine
    • Ornithine
    • Lysine
    • Arginine
  • ==> excess cysteine @ urine ==> precipitation of hexagonal cysteine stones
  • Tx: alkalinization of urine (e.g. K-citrate, acetozolamide)


Homocystinuria: presentation

  • intellectual disability, osteoporosis, tall stature, kyphosis, lens subluzation, thrombosis, atherosclerosis
  • increased homocysteine in urine
  • types:
    • cystathione synthase deficiency
      • tx = decrease methionine, increase cysteine, increase B12 & folate in diet
    • decreased cystathione synthase fxn
      • tx = increase B6++,  increase cysteine in diet
    • homocysteine methyltransferase deficiency
      • tx = increased methionine in diet


Maple syrup urine disease

  • urine smells like maple syrup
  • due to blocked degredations of branched amino acids
    • isoleucine
    • leucine
    • valine
    • ("I Love Vermont" maple syrup)
  • ==> increased alpha-keto acids @ blood
  • ==> CNS defects, intellectual disability, death
  • tx: restrict aa + add thiamine

Decks in USMLE Step 1 Class (97):