Metabolic Disease

Question 1

overflow

Answer 1

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)

Question 2

renal disorder

Answer 2

due to lack of reabsorption in tubules caused by tubular defects when plasma levels are normal

Question 3

most common abnormalities

Answer 3

overflow disorders ( as opposed to renal)

Question 4

Primary aminoaciduria definition

Answer 4

known as inborn errors of metabolism
inherited defect
2 types
1. enzyme is defective/deficient
2. tubular reabsorption dysfunction

Question 5

secondary aminoaciduria definition

Answer 5

due to other causes such as severe liver disease or generalized renal tubular dysfunction

Question 6

Cystinuria general

Answer 6

inherited autosomal recessive
renal aminoaciduria (!)
defective tubular reabsorption of cystine, arginine, lysine & ornithine

Question 7

clinical signs of cystinuria

Answer 7

formation of calculi & cystine stones - because cystine is less soluble than the other amino acids that are not reabsorbed

Question 8

ways to avoid stone formation

Answer 8

staying well hydrated & D-penicillamine

Question 9

Screening tests for Cystinuria

Answer 9

cystine crystals (!!!) in the urine
cyanide-nitroprusside test= red-purple (!)

Question 10

Cystinosis general

Answer 10

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

Question 11

clinical symptoms of cystinosis

Answer 11

growth retardation, ricketts, acidosis, polydipsia, polyuria

severe cases = renal failure

Question 12

treatment for cystinosis

Answer 12

renal dialysis
cystine-depleting medications
transplant
if not treated, most patients die by 10 years of age due to renal damage

Question 13

screening tests for cystinosis

Answer 13

cyanide-nitroprusside test= red-purple (!)

clinitest - orange-red

Question 14

Homocystinuria general

Answer 14

lack enzyme cystathione synthase= converts homocysteine to cystathione which is needed for brain development

Question 15

screening tests for homocystinuria

Answer 15

cyanide-nitroprusside= positive

silver nitroprusside test - only homocystine will react (not cystine)

Question 16

Maple Syrup urine disease

Answer 16

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

Question 17

newborn symptoms of maple syrup urine disease

Answer 17

acute ketoacidosis
vomiting
seizures
lethargy
urine has distinctive maple syrup odor due to rapid accumulation of ketoacids

Question 18

screening test for maple syrup urine disease

Answer 18

2,4-dinitropenylhydrazine (DNPH)= yellow
ferric chloride = green-gray
diagnosis is made by amino acid analysis using MS/MS

Question 19

Phenylketonuria general

Answer 19

inherited, autosomal recessive
deficient/defective phenylalanine hydroxylase
results in buildup of phenylketones in serum & urine

Question 20

clinical symptoms of phenylketonuria

Answer 20

delayed development & feeding difficulties
‘mousy’ or ‘musty’ odor of urine (!!)
decreased skin pigmentation (!!)
increased plasma levels of phenylalanine leads to brain injury /mental retardation

Question 21

screening test for phenylketonuria

Answer 21

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

Question 22

Alkaptonuria general

Answer 22

rare, recessive disease

deficient/defective enzyme homogentisic acid oxidase causing a buildup of homogentisic acid

Question 23

clinical symptoms of alkaptonuria

Answer 23

ochronosis- abnormal dark blue or black tissue pigmentation
degenerative arthritis
urine darkens after becoming alkaline (!!)

Question 24

screening test for alkaptonuria

Answer 24

ammonical silver nitrate- black color
benedict’s test- yellow precipitate
ferric chloride- transient deep blude
confirmatory- TLC or HPLC

Question 25

Tyrosinuria causes

Answer 25

several causes:
transient-immature liver
acquired severe liver disease
hereditary disorder: no enzymes are produced; usually fatal

Question 26

lab findings of tyrosinuria

Answer 26

tyrosine & leucine crystals

‘cabbage-like’ odor to urine (!!)

Question 27

screening test for tyrosinuira

Answer 27

nitrosonaphthol test - non specific for urine

ferric chloride- transient green

Question 28

Melanuria general

Answer 28

increased melanin due to a malignant melanoma

urine darkens when exposed to air or sunlight (!!)

Question 29

melanuria screening test

Answer 29

must be differentiated from alkaptonuria (also turns black)
ferric chloride- gray or black precipitate (!)
sodium nitroprusside- red
ehrlich’s reagent- red

Question 30

Galactosuria general

Answer 30

inherited autosomal recessive defect in CHO metabolism
deficiency- galactose-1-phosphate uridyl transferase
galactose cannot be converted to glucose

Question 31

complications/ tests for galactosuria

Answer 31

w/o treatment, infants often die of E. coli sepsis; if not, mentally/physically retarded by 3-4 months
clinitest- positive
TLC to confirm

Question 32

Phenylalanine-tyrosine disorders (list)

Answer 32

phenylketonuria-phenylalanine hydroxylase
alkaptonuria-homogentisic acid oxidase
tyrosinuria
melanuria

Question 33

cystine disorders (list)

Answer 33

cystinuria-defective tubular reabsorption
cystinosis- cystine deposition
homocystinuria- cystathione synthase