Biochem - Disorders of Metabolism

Question 1

Glucose 6-phoshate dehydrogenase deficiency

Answer 1

decrease NADPH in RBCs -> hemolytic anemia d/t poor RBC defense against oxidizing agents (OXIDATIVE DAMAGE)
XR, >African American, incr malarial resistance
Heinz bodies - denatured globin chains precipitate within RBCs d/t oxidative stress
Bite cells - result from phagocytic removal of Heinz bodies by splenic macrophages

Question 2

essential fructosuria

Answer 2

defect in FRUCTOKINASE, AR
benign, asymptomatic
hexokinase becomes pathway of converting fructose to fructose 6-phosphate
symptoms: fructose in blood/urine

Question 3

hereditary fructose intolerance

Answer 3

defect in ALDOLASE B, AR
fructose 1-phosphage accumulates -> decrease available phosphate -> inhibit glycogenolysis and gluconeogenesis
symptoms following consumption of fruit, juice or honey
reducing sugar detected in urine
symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
treatment: decrease intake of both fructose and sucrose

Question 4

galactokinase deficiency

Answer 4

defect in GALACTOKINASE, AR
galactitol accumulates if galactose present in diet
symptoms: galactosemia, galactosuria, infantile cataracts
may present w/ failure to track objects or to develop a social smile

Question 5

classic galactosemia

Answer 5

absence of GALACTOSE-1-PHOSPHAGE URIDYLTRANSFERASE, AR
accumulation of toxic substances (galactitol)
symptoms develop when infant begins feeding -> failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
[predispose neonates to E. coli sepsis]
treatment: exclude galactose and lactose from diet

Question 6

ornithine transcarbamylase deficiency

Answer 6

urea cycle disorder, XR
interferes w/ body’s ability to eliminate ammonia
excess carbamoyl phosphate -> orotic acid
findings: increase orotic acid in blood and urine, decrease BUN, symptoms of hyperammonemia
NO MEGALOBLASTIC ANEMIA

Question 7

Phenylketonuria

Answer 7

decrease phenylalanine hydroxylase or decrease tetrahjydrobiopterin cofactor, AR
tyrosine becomes essential
increase phenylalanine -> phenyl ketonuria
findings: intellectual disability, growth retardation, seizures, fair complexion, eczema, musty body odor (disorder of aromatic amino acid metabolism)
treatment: decrease phenylalanine and increase tyrosine

Question 8

maple syrup urine disease

Answer 8

blocked degradation of branched amino acids (isoleucine, leucine, valine) d/t decrease branched-chain α-ketoacid dehydrogenase (B1) -> increase α-ketoacids in blood, AR
causes severe CNS defects, intellectual disability, and death
presentatioN: vomiting, poor feeding, urine smells like maple syrup/burnt sugar
treatment: restrict isoleucine, leucine, valine in diet, thiamine supplementation

Question 9

alkaptonuria

Answer 9

congenital deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate -> pigment-forming homogentisic acid accumulation in tissue, AR
usually benign
findings: bluish-black connective tissue, ear cartilage, and sclerae; urine turns black w prolonged exposure to air
may have debilitating arthralgias

Question 10

homocystinuria

Answer 10

All AR:
cystathione synthase deficiency (tx: decr methionine, incr cysteine, incr B6, B12, and folate)
decr affinity of cystathione synthase for pyridoxal phosphate (tx: marked incr B6 and incr cysteine)
methionine synthase deficiency (tx: incr methionine)
presentation:
incr homocysteine in urine
Osteoporosis
Marfanoid habitus
Ocular changes (downward and inward lens subluxation)
Cardiovascular effects (thrombosis and atherosclerosis -> stroke and MI)
kyphosis
intellectual disability

Question 11

cystinuria

Answer 11

hereditary defect in renal PCT and intestinal amino acid transporter that prevents resorption of cystine, ornithine, lysine, and arginine (COLA), AR
excess cystine in urine -> recurrent precipitation of hexagonal cystine stones
tx: urinary alkalization and chelating agents, good hydration
dx: urinary cyanide-nitroprusside test