METABOLIC DISORDERS Flashcards
NADPH is necessary to keep glutathione
reduced, which in turn detoxifies free radicals
and peroxides.
bite cells
heinz bodies
Glucose-6-phosphate
dehydrogenase
deficiency
Involves a defect in fructokinase.
fructose appears in blood and urine.
Essential fructosuria
Hereditary deficiency of aldolase B
hypoglycemia, jaundice, cirrhosis, vomiting.
Hereditary fructose
intolerance
Hereditary deficiency of galactokinase.
galactose appears in blood (galactosemia) and urine (galactosuria); infantile cataracts.
Galactokinase
deficiency
Absence of galactose-1-phosphate uridyltransferase.
Symptoms develop when infant begins feeding (lactose present in breast milk and routine formula)
and include failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability.
Classic galactosemia
An alternative method of trapping glucose in the cell is to convert it to its alcohol counterpart,
sorbitol, via aldose reductase.
tissues with an insufficient amount/activity of this enzyme are at risk of
intracellular sorbitol accumulation, causing osmotic damage (eg, cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in diabetes).
Sorbitol
Insufficient lactase enzyme dietary lactose intolerance. Lactase functions on the intestinal brush
border to digest lactose (in milk and milk products) into glucose and galactose.
Bloating, cramps, flatulence, osmotic diarrhea.
Lactase deficiency
Can be acquired (eg, liver disease) or hereditary (eg, urea cycle enzyme deficiencies).
Presents with flapping tremor (eg, asterixis),
slurring of speech, somnolence, vomiting,
cerebral edema, blurring of vision.
Hyperammonemia
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 (part of the pyrimidine synthesis pathway).
Ornithine
transcarbamylase
deficiency
Due to phenylalanine hydroxylase or
tetrahydrobiopterin (BH4) cofactor (malignant PKU).
Tyrosine becomes essential. phenylalanine increases and leads to increase in phenyl ketones in urine.
Findings: intellectual disability, growth
retardation, seizures, fair complexion, eczema,
musty body odor.
Phenylketonuria
Blocked degradation of branched amino
acids (Isoleucine, Leucine, Valine) due to branched-chain α-ketoacid dehydrogenase
(B1).
Causes α-ketoacids in the blood, especially those of leucine.
Maple syrup urine
disease
Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate leading to pigment-forming homogentisic acid builds up in tissue
bluish-black connective tissue, ear cartilage, and sclerae (ochronosis); urine turns black on
prolonged exposure to air.
Alkaptonuria
Cystathionine synthase deficiency
decrease affinity of cystathionine synthase for pyridoxal phosphate
Methionine synthase
Methylenetetrahydrofolate reductase
Homocystinuria
Hereditary defect of renal PCT and intestinal
amino acid transporter that prevents
reabsorption of Cystine, Ornithine, Lysine, and Arginine
Excess cystine in the urine can lead to recurrent precipitation of hexagonal cystine stones
Cystinuria
Most commonly present in infancy with poor feeding, vomiting, hypotonia, high anion gap metabolic acidosis, hepatomegaly, seizures.
Organic acidemias
