PATH - Metabolism Deficiencies Flashcards
Pyruvate dehydrogenase complex deficiency
X-linked
Causes a buildup of pyruvate that gets shunted to *lactate (via LDH) and *alanine (via ALT).
Findings: Neurologic defects, lactic acidosis, INC serum *alanine starting in infancy
TX
INC intake of ketogenic nutrients (eg, high fat
content or INC *lysine and *leucine).
Lysine and Leucine—the onLy pureLy ketogenic
amino acids.
Glucose-6-phosphate
dehydrogenase deficiency
X-linked recessive disorder
most common human enzyme deficiency
INC malarial resistance.
NADPH is necessary to keep *glutathione reduced, which in turn detoxifies free radicals and peroxides
DEC NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents (eg, fava beans, sulfonamides, primaquine, antituberculosis
drugs)
*Heinz bodies—denatured Hemoglobin precipitates within RBCs due to oxidative
stress.
*Bite cells—result from the phagocytic removal of Heinz bodies by splenic macrophages.
Think, “Bite into some Heinz ketchup.”
Infection (most common cause) can also precipitate hemolysis; inflammatory
response produces free radicals that diffuse
into RBCs, causing oxidative damage
Essential fructosuria
Autosomal recessive
Involves a defect in *fructokinase
A benign, asymptomatic condition
SX: fructose appears in blood and urine.
Fructose intolerance
Autosomal recessive
Hereditary deficiency of *aldolase B.
*Fructose-1-phosphate accumulates, results in inhibition of glycogenolysis and gluconeogenesis
Symptoms present *following consumption of fruit, juice, or honey.
Urine dipstick will be⊝ (tests for glucose only); reducing sugar can be detected in the urine
SX: hypoglycemia, jaundice, cirrhosis, vomiting.
TX: DEC intake of both fructose and sucrose (glucose + fructose).
Fructose is to Aldolase B as Galactose is to UridylTransferase (FAB GUT).
Galactokinase deficiency
Autosomal recessive
Hereditary deficiency of *galactokinase
*Galactitol accumulates
Symptoms develop when infant *begins feeding (lactose present in breast milk and routine formula)
Symptoms: galactose appears in blood (galactosemia) and urine (*galactosuria); infantile cataracts.
May present as failure to track objects or to develop a social smile.
Classic galactosemia
Autosomal recessive
Absence of *galactose-1-phosphate uridyltransferase
SX: failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability. Can lead to E coli sepsis in neonates.
TX: exclude galactose and lactose (galactose + glucose) from diet.
Fructose is to Aldolase B as Galactose is to UridylTransferase (FAB GUT).
Lactase deficiency
Insufficient lactase enzyme–>dietary lactose intolerance
*Primary: age-dependent decline *after childhood (absence of lactase-persistent allele), common in
people of Asian, African, or Native American descent.
- Secondary: loss of brush border due to gastroenteritis (eg, rotavirus), autoimmune disease, etc.
- Congenital lactase deficiency: rare, due to defective gene
SX: Bloating, cramps, flatulence, osmotic diarrhea
Stool demonstrates DEC pH and breath shows INC hydrogen content with lactose hydrogen breath test.
Intestinal biopsy reveals normal mucosa in patients with hereditary lactose intolerance.
Hyperammonemia
Results in excess NH3, which depletes α-ketoglutarate, leading to inhibition of TCA cycle.
Ammonia accumulation—tremor (*asterixis),
slurring of speech, somnolence, vomiting,
cerebral edema, blurring of vision
TX: limit protein in diet
N-acetylglutamate synthase deficiency
urea cycle disorder
Required cofactor for carbamoyl phosphate synthetase I.
Absence of N acetylglutamate–>hyperammonemia
Presents in neonates as poorly regulated respiration and body temperature, poor feeding, developmental delay, intellectual disability (identical to presentation of carbamoyl phosphate synthetase I deficiency).
Ornithine transcarbamylase
deficiency
X-linked recessive
Most common urea cycle disorder.
Interferes with the body’s ability to eliminate ammonia.
Often evident in the first few days of life, but may present later.
Excess carbamoyl phosphate is converted
to orotic acid
Findings: INC orotic acid in blood and urine, DEC BUN, symptoms of hyperammonemia.
No megaloblastic anemia (vs orotic aciduria).
