SCREENING FOR METABOLIC DISORDER Flashcards by Ssherwyn Lavarias

Urine may contain additional abnormal substances not tested
by routine urinalysis - can be detected or monitored by additional
abnormal screening tests that can also be performed in
urinalysis laboratory.

SCREENING FOR METABOLIC DISORDER

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METABOLIC DISORDERS CAUSES

Overflow
Renal
Inborn error of metabolism

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Result from disruption of a normal metabolic pathway
that causes increased plasma concentrations of amino
acids (non-metabolize substances) that either override
the reabsorption ability of the renal tubules or are
not normally reabsorbed from the filtrates

OVERFLOW

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Due to defective tubular reabsorption of amino acids

RENAL

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Failure to inherit a gene that codes for a particular
enzyme

INBORN ERROR OF METABOLISM (IEM)

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Testing for many substances is now performed using
Tandem Mass Spectrophotometry (MS/MS)

INBORN ERROR OF METABOLISM (IEM)

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It is
capable of screening infant blood sample for specific
substances associated with particular IEMs

Tandem Mass Spectrophotometry (MS/MS

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Newborn Screening Tests

o Phenylketonuria
o MSUD
o Isovaleric Acidemia
o Cystinuria
o Cystinosis
o Homo-cystinuria
o Congenital hypothyroidism
o Congenital hyperplasia
o Galactosemia
o G6PD

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Homogentisic
acid color

Black

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Melanin color

Black

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Indican color

Dark or bluish color

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Porphyrins color

(pink
to reddish-brown
or purple)

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Phenylketonuria odor

mousy
odor

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Maple syrup
urine disease

(sweet or syrup or
burnt sugar

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Isovaleric
acidemia

(sweaty
feet

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Cystinuria
Cystinosis
Homocystinuria
Odor

(rotten
egg order)

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What are the crystals produce in ABNORMAL METABOLIC CONSTITUENTS OR
CONDITIONS DETECTED IN THE ROUTINE URINALYSIS

Cystine
Leucine
Tyrosine
Lesch-Nyhan disorder

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Most well-known aminoaciduria that can lead to
mental retardation

PHENYLKETONURIA (PKU)

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(-) gene that codes for Phenylalanine Hydroxylase

PHENYLKETONURIA (PKU)

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PKU is (-) gene that codes for _____

Phenylalanine Hydroxylase

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Screening Tests for PKU

FeCl3 tube test = (+) blue-green color
o Phenistix strip = (+) gray to gray-green color

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Positive result for FeCl3 tube test in PKU

(+) blue-green color

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Positive result for phenistox strip in PKU

(+) gray to gray-green color

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Most well-known test for PKU
• Obtain a blood sample from the heel-stick and placed
on filter paper disks and placed in culture media

GUTHRIE BACTERIAL INHIBITION TEST (GUTHRIE’S
MICROBIAL INHIBITION ASSAY)

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B.subtilis is cultured with ____

Beta-2-thienylalanine (TE)

B2-TE inhibits the growth of

B.subtilis

It counteracts the action of B2-TE

Phenylalanine

accumulation of excess tyrosine in the plasma (tyrosinemia) producing urinary overflow

TYROSYLURIA

TYROSYLURIA is (-) for a gene that decodes for:

o Type 1: Fumarylacetoacetate hydrolase (FAH) o Type 2: Tyrosine aminotransferase o Type 3: p-hydroxyphenylpyruvic acid dioxygenase

May also be seen in patients with severe liver disease (will produce tyrosine and leucine crystals)

TYROSYLURIA

TYROSYLURIA urine odor

"Rancid butter" odor

Screening and confirmatory test for tyrosyluria

Screening: Nitrosonaphthanol • Confirmatory: Chromatography

• Deficiency in homogentisic acid oxidase • Increased homogentisic acid • Produces brown pigment deposits in body tissues that can lead to arthritis, and liver and cardiac problems.

ALKAPTONURIA

ALKAPTONURIA screening tests

• Screening Test o Ferric chloride tube test o Benedict's test o Alklinization of fresh urine

Increased urinary melanin that produces a darkening of urine • Indicates malignant melanoma

MELANURIA

Screening test for MELANURIA

• Screening: o FeCl3 tube test o Sodium nitroprusside test o Ehrlich test

This differ from other amino acids by having a methyl (-CH3) group that branches from the main aliphatic carbon chain

BRANCHED-CHAIN AMINOACIDURIAS

Two major groups of BRANCHED-CHAIN AMINOACIDURIAS

1. Accumulation of one or more of the early amino acid degradation products (ex: MSUD) 2. Accumulation of organic acids produced further down in the amino acid metabolic pathway - Organic acidemias (isovaleric, propionic, methylmalonic)

Clinical findings of BRANCHED-CHAIN AMINOACIDURIAS

Ketonuria

Most common IEM in the Philippines

MAPLE SYRUP URINE DISEASE

MAPLE SYRUP URINE DISEASE (-) Gene that encodes for the enzyme for metabolism of the ketoacids of ______

Leucine, Isoleucine and Valine

• Causes severe mental retardation, convulsions, acidosis, and hypoglycemia if untreated • Death occurs during first year

MAPLE SYRUP URINE DISEASE

Screening test for MAPLE SYRUP URINE DISEASE

o 2,4-dinitrophenylhydrazine o FeCl3 tube test

• Generalized symptoms o early severe illness, often with vomiting accompanied by metabolic acidosis; hypoglycemia; ketonuria; and increased serum ammonia

ORGANIC ACIDEMIAS

Most commonly encounted disorders in ORGANIC ACIDEMIAS

o Isovaleric acidemia - "sweaty feet" urine odor o Propionic acidemia o Methylmalonic acidemia - detected using pnitroaniline test

"sweaty feet" urine odor

Isovaleric acidemia

detected using pnitroaniline test

Methylmalonic acidemia

increased urinary excretion of the metabolites indican and 5-hydroxyindoleacetic acid

TRYPTOPHAN AMINOACIDURIA

TRYPTOPHAN AMINOACIDURIA usually seen in cases of _____

argentaffinoma

a metabolite in serotonin)

5-hydroxyindoleacetic acid

increased amounts of tryptophan are converted to indole Seen in intestinal disorders: o Obstruction o Presence of abnormal bacteria o Hartnup disease = Blue diaper syndrome

INDICANURIA

INDICANURIA screening test

Obermayer's test

INDICANURIA urine color

Indigo blue

• Degradation product of serotonin (Serotonin is produced from tryptophan by argentaffin cells in the intestines) • Argentaffin cell tumors

5-HYDROXYINDOLEACETIC ACID

Screening test for 5-HYDROXYINDOLEACETIC ACID

o FeCl3 tube test o Nitrosonaphthol with nitrous acid

Patient prep for 5-HYDROXYINDOLEACETIC ACID

Avoid eating foods rich in serotonin

A condition marked by elevated amounts of the amino acid cystine in the urine

CYSTINURIA

Due to inability of the renal tubules to reabsorb cystine filtered by the glomerulus

CYSTINURIA

CYSTINURIA Defective reabsorption:

Cystine, Ornithine, Lysine, and Arginine

It is Sulfur odor urine

CYSTINURIA

(-) gene that codes for an enzyme responsible from cystine metabolism

CYSTINOSIS

Cystine deposits in many areas of the body, what are they?

BM, cornea, lymph nodes and internal organs)

(-) gene that codes for the enzyme cystathione beta- synthase

HOMOCYSTINURIA

TESTS FOR CYSTINURIA AND CYSTINOSIS

-Brand's Modification of Legal's nitroprusside test -Thin layer or Ion-exchange chromatography -High-voltage electrophoresis

Brand's Modification of Legal's nitroprusside test reagent?

Cyanide nitroprusside

Seen in Lead Poisoning

PORPHYRIN DISORDERS

What is the gene that decode for, for the disorder: -Acute intermittent porphyria

Uroporphyrinogen synthase

Defect in the metabolism of the amino acid methionine (leads to increased homocystine)

HOMOCYSTINURIA

HOMOCYSTINURIA is detected by?

silver-nitroprusside test

CDC recommends analysis of (___________) for the presence of free-erythrocyte protoporphyrin as a screening test for lead poisoning

whole blood

What is the gene that decode for, for the disorder: - ALA hydratase def porphyria

ALA synthase

What is the gene that decode for, for the disorder: - congenital erythropoietic porphyria

Uroporphyrinogen cosynthase

What is the gene that decode for, for the disorder: -Porphyria cutanea tarda

Uroporphyrinogen decarboxylase

What is the gene that decode for, for the disorder: -Hereditary coproporphyria

Coproporphyrinogen oxidase

What is the gene that decode for, for the disorder: -Variegate porphyria

Protoporphyrinogen oxidase

Screening Tests specimen used?

urine, blood, stool

Detects d-ALA and porphobilinogen

Ehrlich’s reaction

Test for uroporphyrin, coproporphyrin, and protoporphyrin: violet/ pink/red

Fluorescence at 550-600nm

Accumulation of incompletely metabolized polysaccharide portions in the lysosome

Mucopolysaccharide Disorders

CDC-recommended test for lead poisoning

FEP

mucopolysaccharides accumulate in the cornea; skeletal structure abnormality and severe mental retardation

HURLER

skeletal structure abnormality and severe mental retardation

HUNTER

mental retardation only

SANFILIPO

cetylmethylammonium bromide test = white turbidity

CETYLTRIMETHYLAMMONIUM BROMIDE TEST (CTAB)

massive excretion of uric acid crystals in the urine caused by the failure to inherit the gene to produce hypoxantine guanine phosphoribosyltransferase; “orange sand” in diaper

Lesch-Nyhan Disease

It is purine disease

Lesch-Nyhan Disease