Metabolic Disease Flashcards
overflow
due to increase in plasma levels exceeding the renal threshold
OR
due to increase in urine caused by lack of reabsorption by tubules when plasma levels are elevated (no threshold)
renal disorder
due to lack of reabsorption in tubules caused by tubular defects when plasma levels are normal
most common abnormalities
overflow disorders ( as opposed to renal)
Primary aminoaciduria definition
known as inborn errors of metabolism inherited defect 2 types 1. enzyme is defective/deficient 2. tubular reabsorption dysfunction
secondary aminoaciduria definition
due to other causes such as severe liver disease or generalized renal tubular dysfunction
Cystinuria general
inherited autosomal recessive renal aminoaciduria (!) defective tubular reabsorption of cystine, arginine, lysine & ornithine
clinical signs of cystinuria
formation of calculi & cystine stones - because cystine is less soluble than the other amino acids that are not reabsorbed
ways to avoid stone formation
staying well hydrated & D-penicillamine
Screening tests for Cystinuria
cystine crystals (!!!) in the urine cyanide-nitroprusside test= red-purple (!)
Cystinosis general
inborn error of metabolism- recessive
intracellular deposition of cystine in lysosomes of all body cells, especially in kidney, eye, bone marrow & spleen
2ndary effect on proximal renal tubule- cystine crystals accumulate in PT= fanconi’s syndrome develops
clinical symptoms of cystinosis
growth retardation, ricketts, acidosis, polydipsia, polyuria
severe cases = renal failure
treatment for cystinosis
renal dialysis
cystine-depleting medications
transplant
if not treated, most patients die by 10 years of age due to renal damage
screening tests for cystinosis
cyanide-nitroprusside test= red-purple (!)
clinitest - orange-red
Homocystinuria general
lack enzyme cystathione synthase= converts homocysteine to cystathione which is needed for brain development
screening tests for homocystinuria
cyanide-nitroprusside= positive
silver nitroprusside test - only homocystine will react (not cystine)
Maple Syrup urine disease
rare, inherited, autosomal recessive
accumulation of branched-chain amino acids - leucine, isoleucine & valine
defect or deficiency in enzyme responsible for normal oxidative decarb to acyl-CoA derivatives
newborn symptoms of maple syrup urine disease
acute ketoacidosis vomiting seizures lethargy urine has distinctive maple syrup odor due to rapid accumulation of ketoacids
screening test for maple syrup urine disease
2,4-dinitropenylhydrazine (DNPH)= yellow
ferric chloride = green-gray
diagnosis is made by amino acid analysis using MS/MS
Phenylketonuria general
inherited, autosomal recessive
deficient/defective phenylalanine hydroxylase
results in buildup of phenylketones in serum & urine
clinical symptoms of phenylketonuria
delayed development & feeding difficulties
‘mousy’ or ‘musty’ odor of urine (!!)
decreased skin pigmentation (!!)
increased plasma levels of phenylalanine leads to brain injury /mental retardation
screening test for phenylketonuria
guthrie microbial inhibition test (blood)-if phenylalanine is increased it will counteract the action of the inhibitor in the test & the microbes will grow
ferric chloride test= green-gray
Alkaptonuria general
rare, recessive disease
deficient/defective enzyme homogentisic acid oxidase causing a buildup of homogentisic acid
clinical symptoms of alkaptonuria
ochronosis- abnormal dark blue or black tissue pigmentation
degenerative arthritis
urine darkens after becoming alkaline (!!)
screening test for alkaptonuria
ammonical silver nitrate- black color
benedict’s test- yellow precipitate
ferric chloride- transient deep blude
confirmatory- TLC or HPLC
