Urine Screening of

Metabolic Disorders

Overflow vs Renal Disorders

Overproduction of a
Overflow
normal
or abnormal
substance to the point
that the tubules are
not able to prevent it
from escaping into the
urine.
Increased levels in
blood & urine
Inherited defect
Acquired defect

Renal

Faulty tubular
reabsorption mechanism
Increased levels seen in
urine only

Value of Urinalysis

Value of Urinalysis

Phenylketonuria (PKU)

Mousy odor urine

1/10,000 - 20,000 births
Autosomal recessive trait
Absence of phenylalanine
hydroxylase
Urinalysis
Follow-up procedure in doubtful Dx
cases
Screening test for proper dietary
control in previously Dx cases
Monitoring the dietary intake of
pregnant women known to lack
phenylalanine hydroxylase

Phenylketonuria Diagnostic
Urinalysis
Tests
Place 1 mL of urine in a

Microbial inhibition test

(Guthrie)

1.

2.

3.

tube.
Slowly add 5 qtts.of
10% ferric chloride.
Observe color

permanent blue green color

(+)

Uses Bacillus subtilis

(+) Phenylalanine
counteracts the action of 2-thienylalanine,
an inhibitor of B. subtilis
(present in the media)
growth is observed

Tyrosyluria

urine may contain excess tyrosine or its

degradation products, phydroxyphenylpyruvic acid and phydroxyphenyllactic acid.

Transitory tyrosinemia in premature infants

Acquired severe liver diseases

Enzyme deficiency

Autosomal Recessive

Type I - no fumarylacetoacetate hydrolase

(FAH)
Type II no tyrosine aminotransferase
Type III - p-hydroxyphenylpyruvic acid
dioxygenase
Tested with nitroso-naphthol test and

Clinical Presentations &

Lab Dx

Melanuria

Tyrosine metabolized further to melanin,

thyroxine, epinephrine, protein and tyrosine
sulfate
Deficiency albinism
Increased in urine urine darkening (after
exposure to air)

Proliferation of melanocytes
malignant melanoma
Tumors secrete 5,6- dihydroxyindole
melanogen melanin

Melanin may react with Na nitroferricyanide

(acetone rgt. Strip) may producer ed color

Ferric chloride tube test, a gray or black

Alkaptonuria

(Alkali lover)

One of the 6 IEM described by Garrod

(1902)
No Homogentisic acid oxidase HA
accumulation

Brown or black-stained cloth or reddishstained disposable diapers

May progress to arthritis, liver and

cardiac disorders

Ferric chloride test deep blue color

Clinitest yellow ppt.

Addition of alkali in urine urine

darkening
AgNO3 test, paper and TLC

Amino Acid Disorders

(Branched-Chain Amino Acid
Disorders)

Having a methyl group that branches from

the main aliphatic C chain

Maple Syrup Urine

Disease

Inherited as autosomal
recessive trait

Failure to inherit gene for

enzyme capable of oxidative
decarboxylation of ketoisovaleric, ketoisocaproic, -keto-methylvaleric

Exhibit failure to thrive w/in

1 wk

Maple Syrup odor is due to

rapid accumulation of ketoacids

Organic Acidemias

Sx: Early severe illness,

vomiting, metabolic acidosis,
hypoglycemia, ketonuria and
increased serum NH3

Commonly:

Isovaleric acidemia

Propionic acidemia

Methylmalonic acidemia

Isovaleric acidemia sweaty

feet urine due to accumulation of
isovaleryl glycine w/o isovaleryl
CoA

Amino Acid Disorders

(Tryptophan Disorders)

Indicanuria

Due to obstruction, abnormal bacteria present,

malabsorption syndromes, Hartnup disease

Blue diaper syndrome

5-hydroxyindoleacetic acid (5-HIAA)

Carcinoid tumors involving argentaffin excess amounts

of serotonin increased urinary 5-HIAA levels
Addition of nitrous acid and 1-nitroso-2-naphthrol
purple to black urine
>25 mg/24h indicates tumor

Cystine
Disorders (Sulfur-like odor
Inability of renal tubules
to reabsorb cystine
urine)

Only amino acid found

during
analysis of calculi
Cystinuria
Has two modes of
inheritance

Poor reabsorption of all

four amino acidscystine,
lysine, arginine, and
ornithine
cystine and lysine are not
reabsorbed

Tested by cyanidenitroprusside test redpurple color

Cystinosis
Genuine
IEM, can be
nepropathic/nonnepropathic

Subdivided as infantile
and late-onset
cystinosis

Defect in lysosomal
membranes

Leads to crystalline
deposits in cornea, bone
marrow, lymph nodes,
and internal organs

Cystinosis (contd)

Fanconi syndrome

Renal transplants and cystinedepleting meds extend lives

from renal failure

Nonnephropathic benign but

may cause ocular disorders

Infantile nephropathic cystinosis

Lab dx: poluria, generalized

aminoaciduria, (+) Clinitest for
reducing substances, lack of
urinary concentration

Homocystinuria

Defect in metabolism of methionine

Leads to failure to thrive, cataracts and mental

retardation, thromboembolic problems, and death

(+) with cyanide-nitroprusside test

Silver nitroprusside test confirms presence

Thromboembolism is related with:

Endothelial cell damage

Smooth muscle cell proliferation
Lipid peroxidation
Upregulation of prothrombotic factors (XII and V)
Downregulation of antithrombotic factors or endothelialderived nitric oxide

Porphyrin Disorders

Porphyrin heme intermediate

Free erythrocyte protoporphyrin

CDC screening test for Pb poisoning

Pophyrias commonly due to lead

poisoning, excessive alcohol intake,
iron deficiency, chronic liver disease
and renal disease

Rarity: Inherited porphyrias >

Acquired

Related with vampirism

Laboratory Diagnosis

Ehrlich reaction - can be

used only for the detection
of ALA and porphobilinogen
Watson-Schwartz reaction differentiation between the
presence of urobilinogen and
porphobilinogen
Hoesch Test
Fluorescence tests does
not distinugish porphyrins

Mucopolysaccharide Disorders

Mucopolysaccharides aka glycosaminoglycans

Incomplete breakdown of polysacchride portion in

lysosomes of CT
Usually found in urine as dermatan, keratan and
heparan sulfates.
Hurler syndrome skeletal structure and mental
retardation; cornea
Hunter syndrome rarely seen in females,
Sanfilippo syndrome only mental retardation
Bone marrow transplants and gene replacement therapy
U/A: Acid-Albumin, Cetyltrimethylammonium bromide
(CTAB) turbdity tests and metachromatic staining spot
tests

Mucopolysaccharidosis

Purine and CHO Disorders

Lesch-Nyhan Disease
Inherited, sex-linked recessive
Without enzyme hypoxanthine guanine
phosphoribosyltransferase
Sx: severe motor defects, mental retardation, tendency
towards self destruction, gout and renal calculi.
Uric acid like orange sand in diapers
Melituria
Pentosuria
Galactosuria failure to thrive, liver disorders, cataracts and
severe mental retardation

Deficiency in GALT, galactokinase, UDP-galactose-4-epimerase

Lactosuria
Fructosuria