URINE SCREENING FOR

METABOLIC DISORDERS
 AMINOACIDURIA
• INCREASE AMINO ACID IN
BLOOD
• INCREASE AMINO ACID IN
URINE
• EXAMPLES: PKU, MSUD
Phenylketunira, maple syrup, Congenital
hypothyroidism, g6pd defeciency
congenital renal hyperplasia
INBORN ERROR OF
METABOLISM!
 FAILURE TO INHERIT A GENE
THAT CODES FOR A PARTICULAR
ENZYME
• NORMAL AMINO ACID IN
BLOOD
• INCREASE AMINO ACID IN
URINE
• Due to defective tubular
reabsorption of amino acids
• EXAMPLES: Cystinuria,
Fanconi’s Syndrome
Newborn screening:
MS tandem spectro: capillary blood
 P h e n y l a l a n i n e a n d Ty r o s i n e M e t a b o l i s m

Green:
disease
associated

Blue:
Enzyme
associate
 PHENYLALANINE-TYROSINE DISORDERS
PHENYLKETONURIA (PKU)
(-) Gene that codes for
Clinical “Mousy Odor” ofhydroxylase
Phenyl -alanine urine
manifestations May lead to severe mental retardation
Abnormal Urinary Phenylalanine, phenyllacetic acid, phenylpyruvic acid
constituents
Tests FeCl3 tube test = ____________________________
Phenistix strip = (+) gray to gray- green color (30s reading time)
_____________________________________
blue green color
Confirmatory: Ion-exchange High Performace Liquid Chromatography
Gapre inhibtion test

Prevention:

Avoid intake of alanine rich food

Milk, bread, rice

Foods to take:
Beans, root crops
 GUTHRIE BACTERIAL INHIBITION TEST!
 sensitive to serum phenylalanine concentrations >4
mg/dL
 Bacillus subtilis is cultured with beta2-thienylalanine
 ___________________inhibits
inhibits the growth the growht of B. subtilis
 Phenylalanine counteracts the action of beta2-
thienylalanine
Tandem Mass Spectrophotometry: best
 PHENYLALANINE-TYROSINE DISORDERS
TYROSYLURIA
(-) Gene that codes for Type I Fumarylacetoacetate hydrolase (FAH)
Type 2_____________________________
Tyrosin aminotransferase
Type 3 p-hydroxyphenylpyruvic acid dioxygenase
Clinical Tyrosine and leucine crystals in urine; liver and renal disease
manifestations (temporary or permanent)
Rancid butter odor of urine
Abnormal Urinary p-hydroxyphenylpyruvic acid and p-hydroxyphenyllactic acid
constituents
Tests FeCl3 tube test = ____________________________
Nitroso-naphthol= Ferric
__________________________
chloride transient test
Confirmatory: Chromatography, Quantitative Serum Assay of tyrosine
(+) orange red *use of nitric acid*
 PHENYLALANINE-TYROSINE DISORDERS
ALKAPTONURIA
(-) Gene that codes for
Absence of gene
Clinical Dark blue to black pigmentation of cartilage and connective
manifestations tissues, liver and cardiac disorders
Urine ____________________________________from
staniding atsettles
room temperature
Abnormal Urinary
constituents
Tests FeCl3Homogentesic acid
tube test = _________________
Bilirubin: clears
Clinitest= (+) yellow precipitate
Transient blue
Alkalinization of fresh urine
Confirmatory: Paper or thin-layer chromatography, Capillary electrophoresis
 PHENYLALANINE-TYROSINE DISORDERS
MELANURIA
(-) Gene that codes for --
Clinical Malignant melanoma
over secretion of melanin in melanocytes
manifestations Due to ______________________________________________
Urine darkens upon air exposure
coritisol, aldosterone,
Abnormal Urinary Melanin
constituents
Tests FeCl3 tube test = (+) Gray/Black ppt
Sodium nitroprusside test = (+) Red
Ehrlich test= _____________

Erlich's reagent
 BRANCHED-CHAIN AMINO ACID DISORDERS
MAPLE SYRUP URINE DISEASE (MSUD)
(-) Gene that codes for Deficiency in decarboxylases and other enzymes needed for the
conversion of ketoamino acids to fatty acids
Clinical Caramelized sugar/Maple syrup odor of urine, failure to thrive,
manifestations mental retardation
__________________________________in blood & urine
Abnormal Urinary Ketoacids (α-ketoisovaleric; α-ketoisocaproic; α-keto,β-
constituents increase leucine, isoleucine, valine
methylvaleric)
Tests 2,4-Dinitrophenylhydrazine (DNPH) test
________________________________
+ yellow turbidity
newborn screening: gold standard
 BRANCHED-CHAIN AMINO ACID DISORDERS
ORGANIC ACIDEMIAS
(-) Gene that codes for 1. ________________= Isovaleryl CoA in the leucine pathway
2. &Isovaleric acidiemia
3. Propionic and Methylmalonic acidemias = Error in the
metabolic pathway converting valine, isoleucine, threonine,
and methionine to succinyl CoA
Clinical 1. Sweaty feet odor of urine
manifestations 2. & 3  Early severe illness, vomiting, metabolic acidosis,
hypoglycemia, increased serum ammonia, ketonuria
Abnormal Urinary Isovalerylglycine
constituents Propionic and methylmalonic acid
Tests Methylmalonic acidemias :
P-nitroaniline test = _______________________

Emerald green
TRYPTOPHAN METABOLISM
 TRYPTOPHAN DISORDERS
INDICANURIA
Clinical  Generalized aminoaciduria (Fanconi’s syndrome)
manifestations  ______________________of urine (upon air exposure)
Seen in:
a) Intestinal disorders
b) Hartnup disease  rare inherited disorder
_____________________________________
Abnormal Urinary also known as BLUE DIAPER SYNDROME
constituents
Tests Indican
Obermayer’s test:
FeCl3 +Urine+ Chloroform  __________________________

FERRI ORBITAL
SWELLING
 TRYPTOPHAN DISORDERS
ARGENTAFFINOMA
ETIOLOGY  Carcinoid tumors involving the
_____________________________________of the intestine
AGENTAFFIN CELLS OR INTEROCHROMAFFIN
Clinical  Vascular and bronchospastic symptoms (carcinoid syndrome)
manifestations
Abnormal Urinary
constituents
5- hiAA (5-hydroxy-indole ACETIC ACID
Tests FeCl3 tube test = (+) Blue-green
Nitroso-naphthol w/ nitrous acid = (+) Violet
*Patient should avoid eating bananas, pineapples & tomatoes

these fruits are rich in

serotonin

bananas, tomato, pineapple

 CYSTINE DSORDERS
CYSTINURIA
ETIOLOGY  Defect in renal tubular reabsorption
 Defective tubular reabsoption of:
1. C_________ = least soluble crystalize in urine
2. O_________
Cysteine
3. L__________
Ornithine soluble in H2O
4. A_________ Converted into:
Leucine
Clinical  Sulfur odor of urine
Arginine
manifestations  Cystine crystals in urine
cysteine
 Formation of urinary calculi
 Fanconi’s syndrome
Abnormal Urinary Cystine, lysine, arginine, ornithine or Cystine and lysine only
constituents
Tests _____________________________________________
Rgt: Cyanide Nitroprusside
BRANDS modification of legal nitroprusside
___________________________

Red- purple color

cystinuria combined with UTI: corps like odor

 CYSTINE DSORDERS
CYSTINOSIS
ETIOLOGY  Regarded as genuine Inborn error of metabolism
 Defect in the lysosomal membranes which prevents the
release of cystine into the cellular cytoplasm for metabolism
Clinical  Deposition of cystine crystals in many areas of the body
manifestations
Abnormal Urinary CYSTINE
Accumulate in the eyes
constituents
Tests Brand’s modification of Legal’s nitroprusside
Rgt: Cyanide Nitroprusside
(+) red-purple color
 CYSTINE DSORDERS
HOMOCYSTINURA
ETIOLOGY  ________________________________________
Absence of cystathaione beta synthase
which leads
to defects in the methionine metabolism thus increasing
homocystine throught the body
Clinical  Failure to thrive, cataracts, mental retardation,
manifestations thromboembolic problems
Abnormal Urinary
constituents
Methionine and homocysteine
Tests Silver-nitroprusside test = (+)_______________
+ red
 MUCOPOLYSACCHARIDE DISORDERS
MUCOPOLYSACCHARIDOSIS
ETIOLOGY  Accumulation of incompletely metabolized polysaccharide
portions in the lysosomes of connective tissue cells and their
increase excretion in the urine
Clinical  _____HURLER_____________ Mental retardation
manifestations Accumulation of mucopolysaccharides in the cornea of the
eyes
 __________________ Sex linked recessive, rarely seen in
females
Hunter syndrome
 __________________No Mental Retardation is the only
abnormality
Sunfillipo
Abnormal Urinary Dermatan sulfate, keratan sulfate, heparan sulfate
constituents
Tests Acid albumin Test= (+) White Turbidity
Screening test: Cetyltrimethylammonium bromide (CTAB) test =
_____________________________
Mucopolysaccharide paper = ______________________
t+turbidity
HUNTER SYNDROME
HURLER SYNDROME

SANFILIPPO SYNDROME
 PURINE DISORDER
(LESCH-NYHAN DISEASE)
ETIOLOGY
Absence of hypo
Clinical  Severe motor defects, mental retardation, tendency
manifestations toward self destruction, gout, renal calculi,
_____________________________________
Abnormal Urinary Uric acid
constituents
Tests Increase Uric acid in the blood

Orange sand diaper

 PORPHYRIN DISORDERS (PORPHYRIAS)
 Urine color = Red/Purple/burgundy-Red/Purplish
Red/Portwine
 Colorless in = Lead poisoning

DISORDER (-) GENE THAT CODES FOR

Ala hydratase Aminolevulinic acid (ALA)
deficiency porphyria Synthetase
Acute intermittent Uroporphyrinogen synthase
porphyria
Congenital Uroporphyrinogen cosynthase
erythropoietic
porphyria
Porphyria cutanea Uroporphyrinogen
tarda decarboxylase
Hereditary Coproporphyrinogen oxidase
coproporphyria
Variegate porphyria Protoporphyrinogen oxidase
  LEAD POISOING inhibits ALA synthase and Ferrochelatase
enzyme

SCREENING TESTS
Specimen:
1. Ehrlich’s reaction
2. Fluorescence at 550-600 nm
3.
___________________________
pre erythrocyte
___________________________
4. The______________________
(Two drops of urine are added to
the Hoesch reagent, which is
Hoesch
Ehrlich’s reagent plus HCl. )
5. Watson-Schwartz test
Urine, Stool, Blood, Bile
Detects d-ALA, porphobilinogen
Test for Uroporphyrin, coproporphyrin &
Protoporphyrin
_________________________________-
CDC +recommended test for Lead poisoning
violet pink flouresence
is a rapid screen for urinary porphobilinogen.
The uppermost part of the solution turns red
in the presence of porphobilinogen.
See your chemical examination or urine
Branzel