AUBF: URINE SCREENING FOR METABOLIC  Inborn Error of Metabolism/IEM – failure to inherit

DISORDERS the gene to produce a particular enzyme or by organ

Romie Solacito, MLS3C malfunction from disease or toxic reactions. \
Overflow Versus Renal Disorders
Newborn Screening Tests
 Tandem Mass Spectrophotometry (MS/MS) –
capable of screening the infant blood sample for
specific substances associated with particular IEMs.

AMINO ACID DISORDERS

 The amino acid disorders with urinary screening
tests include phenylketonuria (PKU), tyrosyluria,
alkaptonuria, melanuria, maple syrup urine disease,
organic acidemias, indicanuria, cystinuria, and
cystinosis.

Phenylalanine – Tyrosine Disorders – overproduction of

 Two categories of abnormal metabolic substances in
melanin (PKU, tyrosyluria, and alkaptonuria)
the urine:
 Phenylketonuria/Aminoaciduria/PKU – increase
 Overflow – disruption of a normal metabolic
amount of keto acids (phenylpyruvate). Disrupted
pathway that can causes increased plasma
conversion of phenylalanine to tyrosine.
concentration
o Enzyme Affected: Phenylalanine Hydroxylase
 Renal – malfunctions in the tubular reabsorption
o Diet: Low intake of milk to avoid mental
mechanism
capabilities and aspartame.
 The most frequently encountered overflow
o Laboratory Diagnosis: blood collected after 24
metabolic disorders involved in protein, fat and
hours after birth or 4 hours after birth, if the
carbohydrates (essential for complete metabolism)
cutoff level for normal results is lowered from
4 mg/dL to 2 mg/dL, the presence of PKU
 should be detected. Urine Testing using ferric
chloride – blue green color (positive).
 Tyrosyluria/Tyrosinemia – accumulation of excess
tyrosine in the plasma (tyrosinemia) producing
urinary overflow may be due to several causes and
is not well categorized. inherited or metabolic
defects. Excess tyrosine in urine or presence of p-
hydroxyphenyl pyruvic acid and p-hydroxyphenyl
lactic acid (T2).
o Enzyme/s Affected: Type 1 –
fumarylacetoacetate hydrolase (renal tubular
disorder/liver failure). Type 2 – Tyrosine
Aminotransferase (corneal erosion/lesions on
palms, fingers and soles). Type 3 - p-
hydroxyphenylpyruvic acid dioxygenase.
o Diet: restrictions of phenylalanine and tyrosine
– mental retardation.
o Laboratory Diagnosis: MS/MS. Nitroso-
Naphthol Test for Tyrosine – Orange Red
color (positive).
 Melanuria - Increased urinary melanin darkens the
urine after air exposure. Malignan melanoma –
secretes 5,6-duhyroxyindole.
o Laboratory Diagnosis: sodium nitroferricyanide
(acetone reagent strip) - red color (Positive)
 Alkaptonuria – (brown/black stained) darkened
urine after becoming alkaline from standing at room
temperature. Liver and cardiac disorders.
o Enzyme Affected: homogentisic acid oxidase
o Laboratory Diagnosis: Ferric Chloride Test –
deep blue (positive). Clinitest – yellow
precipitate (positive). Silver Nitrate – black
color (positive). Paper and Thin Layer
Chromatography – quantitating.
Branched-Chain Amino Acid Disorders - two major
groups of disorders are associated with errors in the
metabolism of the branched-chain amino acids
 Maple Syrup Urine Disease – newborn screening,
inherited (IEM). Involve the amino acids (leucine,
isoleucine and valine).
o Enzyme Affected: enzyme able to produce
oxidative decarboxylation
o Laboratory Diagnosis: 2, 4 –
Dinitrophenylhydrazine (DNPH) – yellow
turbidity or precipitate (positive).
 Organic Acidemia – vomiting accompanied by
metabolic acidosis, hypoglycemia, ketonuria, and
 ammonia increased. Can be isovaleric, propionic
and methylmalonic acidemia (isoleucine, valine,
threonine, and methionine to succinyl coenzyme A)
o Enzyme Affected: accumulation of
isovalerylglycine - Isovaleryl coenzyme A in
leucine pathway – sweaty feet odor urine.
o Laboratory Diagnosis: MS/MS
Tryptophan Disorders – increased urinary excretion of
indicant and 5-HIAA.
 Indicanuria – Hartnup disease (increased amounts
of tryptophan are converted to indole and indigo
blue when exposed to air)
 5-Hydroxyindoleacetic Acid/5-HIAA - Serotonin is
produced from tryptophan by the argentaffin cells
in the intestine and it degradation product is 5-HIAA
(2 to 8ml) and when carcinoid tumors occur there’s
an excessive production of serotonin and 5-HIAA.
o Laboratory Diagnosis: nitrous acid and 1-nitroso-
2-naphthol to 24hr urine – purple to
black(positive).
Cystine Disorders – two distinct disorders. It is now
known that although both disorders are inherited, one is
a defect in the renal tubular transport of amino acids
(cystinuria) and the other is an IEM (cystinosis)
 Cystinuria – elevated cystine in urine. Inability of renal
absorption of cystine, lysine, arginine, and ornithine.
o Laboratory Diagnosis: first morning urine for
microscopy. Cyanide-Nitroprusside Test for
Cystine – red purple color(positive)
 Cystinosis – genuine IEM, three variations, ranging
from a severe fatal disorder developed in infancy to a
benign form appearing in adulthood. Can be
nephropathic (infantile or lateonset) and
nonnephropathic (ocular disorder).
 Homocystinuria - Defects in the metabolism of the
amino acid methionine. Develop thrive, cataracts,
mental retardation thromboembolic problems and
death.
o Laboratory Diagnosis: Silver Nitroprusside Test
for Homocystine – red purple (positive)
Porphyrin Disorders - Disorders of porphyrin metabolism
are collectively termed porphyrias.
Mucopolysaccharide Disorders
 Mucopolysaccharides, or glycosaminoglycans, are a
group of large compounds located primarily in the
connective tissue.
 There are many types of mucopolysaccharidoses,
but the best known are Hurler syndrome, Hunter
syndrome, and Sanfilippo syndrome
 In both Hurler and Hunter syndromes, the skeletal
structure is abnormal and there is severe mental
retardation
 Hurler syndrome, mucopolysaccharides accumulate
in the cornea of the eye.
 Hunter syndrome is inherited as sex-linked recessive
and is rarely seen in females.
 Sanfilippo syndrome, the only abnormality is
mental retardation.
 The most frequently used screening tests are the
acid-albumin and cetyltrimethylammonium
bromide (CTAB) turbidity tests and the
metachromatic staining spot tests – thick white
turbidity (positive).

Purine Disorders - disorder of purine metabolism known

as Lesch-Nyhan disease that is inherited as a sex-linked
recessive result in massive excretion of urinary uric acid
crystals.
 Enzyme Affected: hypoxanthine guanine
phosphoribosyltransferase

Carbohydrate Disorders
 The presence of increased urinary sugar (melituria)
is most frequently due to an inherited disorder.
 Galactosuria, indicating the inability to properly
metabolize galactose to glucose. can be caused by a
deficiency in any of three enzymes, galactose-1-
phosphate uridyl transferase (GALT), galactokinase,
and UDP-galactose-4-epimerase.
 Lactosuria may be seen during pregnancy and
lactation.
 Fructosuria is associated with parenteral feeding
 pentosuria with ingestion of large amounts of fruit.