SCREENING FOR METABOLIC DISORDERS Flashcards by Arriane Cyrel (MTI)

Many of the abnormal results obtained in routine urinalysis are related to [?] rather than renal disease

metabolic disorders

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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

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-Result from disruption of a normal metabolic pathway that causes increased plasma concentrations of amino acids

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)

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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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Amino Acid Disorders

Phenylketonuria (PKU)
Tyrosyluria
Alkaptonuria
Melanuria
Maple syrup urine disease(MSUD)
Organic acidemias
Indicanuria
Cystinuria
Cystinosis

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-Aminoacidurias

Phenylketonuria

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-(-) gene that codes for Phenylalanine Hydroxylase

Phenylketonuria

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-“Mousy” urine odor

Phenylketonuria

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Screening Tests:

FeCl3 tube test
Phenistixstrip

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= (+) blue-green color

FeCl3 tube test

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= (+) gray to gray-green color

Phenistixstrip

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•B.subtilisis cultured with Beta-2-thienylalanine (TE)

Guthrie bacterial inhibition test

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•B2-TE inhibits the growth of B.subtilis

Guthrie bacterial inhibition test

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•Phenylalanine counteracts the action of B2-TE

Guthrie bacterial inhibition test

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

Tyrosyluria

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Tyrosyluria (-) for a gene that decodes for:

Type 1: Fumarylacetoacetatehydrolase (FAH)
Type 2: Tyrosine aminotransferase
Type 3: p-hydroxyphenylpyruvicacid dioxygenase

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: Fumarylacetoacetatehydrolase (FAH)

Type 1

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: Tyrosine aminotransferase

Type 2

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: p-hydroxyphenylpyruvicacid dioxygenase

Type 3

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

Tyrosyluria

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-“Rancid butter” odor

Tyrosyluria

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Tyrosyluria Screening:

Nitrosonaphthanol

Tyrosyluria Confirmatory:

Chromatography

-Deficiency in homogentisicacid oxidase

Alkaptonuria

-Increased homogentisicacid

Alkaptonuria

-Produces brown pigment deposits in body tissues that can lead to arthritis, and liver and cardiac problems.

Alkaptonuria

Ferric chloride tube test

Alkaptonuria

Benedict’s test

Alkaptonuria

Alklinizationof fresh urine

Alkaptonuria

-Increased urinary melanin that produces a darkening of urine

Melanuria

-Indicates malignant melanoma

Melanuria

-“black urine”

Melanuria

FeCl3 tube test

Melanuria

Sodium nitroprussidetest

Melanuria

Ehrlich test

Melanuria

The branched-chain amino acids 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: 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

Branched-Chain Aminoacidurias

Clinical Findings: Ketonuria

Branched-Chain Aminoacidurias

-Most common IEM in the Philippines

Maple Syrup Urine Disease

-(-) Gene that codes for the enzyme for metabolism of the ketoacidsof Leucine, Isoleucineand Valine

Maple Syrup Urine Disease

-“Caramelized sugar/Maple syrup/Curry” urine odor

Maple Syrup Urine Disease

-Causes severe mental retardation, convulsions, acidosis, and hypoglycemia if untreated

Maple Syrup Urine Disease

-Death occurs during first year

Maple Syrup Urine Disease

2,4-dinitrophenylhydrazine

Maple Syrup Urine Disease

FeCl3 tube test

Maple Syrup Urine Disease

early severe illness, often with vomiting accompanied by metabolic acidosis; hypoglycemia; ketonuria; and increased serum ammonia

Organic Acidemias

Isovalericacidemia–“sweaty feet” urine odor

Organic Acidemias

Propionic acidemia

Organic Acidemias

Methylmalonicacidemia–detected using p-nitroanilinetest

Organic Acidemias

-increased urinary excretion of the metabolites indicanand 5-hydroxyindoleacetic acid

TRYPTOPHAN AMINOACIDURIA

-increased amounts of tryptophan are converted to indole

Indicanuria

Obstruction

Indicanuria

Presence of abnormal bacteria

Indicanuria

Hartnupdisease = Blue diaper syndrome

Indicanuria

-Indigo blue urine color

Indicanuria

Obermayer’stest

Indicanuria

-Degradation product of serotonin (Serotonin is produced from tryptophan by argentaffincells in the intestines)

5-Hydroxyindoleacetic Acid

-Argentaffincell tumors

5-Hydroxyindoleacetic Acid

FeCl3 tube test

5-Hydroxyindoleacetic Acid

Nitrosonaphtholwith nitrous acid

5-Hydroxyindoleacetic Acid

Pxprep: Avoid eating foods rich in serotonin

5-Hydroxyindoleacetic Acid

-A condition marked by elevated amounts of the amino acid cystinein the urine

Cystinuria

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

Cystinuria

-Defective reabsorption: lysine, arginine, and ornithine, cystine

Cystinuria

-Sulfur odor urine

Cystinuria

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

Cystinosis

-Cystine deposits in many areas of the body (BM, cornea, lymph nodes and internal organs)

Cystinosis

Brand’s Modification of Legal’snitroprussidetest

Reagent: Cyanide nitroprusside

Tests for Cystinuria and Cystinosis

Thin layer or Ion-exchange chromatography

Tests for Cystinuria and Cystinosis

High-voltage electrophoresis

Tests for Cystinuria and Cystinosis

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

Homocystinuria

-(-) gene that codes for the enzyme cystathione betasynthase

Homocystinuria

-Detected by silver-nitroprusside test

Homocystinuria

-Disorders of porphyrin metabolism

PorphyrinDisorders

-Urine color: Red, purple, burgundy red, purplshred, Port wine

PorphyrinDisorders

-Lead Poisoning

PorphyrinDisorders

ALA synthetase

ALA hydratasedefporphyria

Uroporphyrinogen synthase

Acute Intermittent porphyria

Uroporphyrinogen cosynthase

Congenital erythropoietic porphyria

Uroporphyrinogen decarboxylase

Porphyria cutanea tarda

Coproporphyrinogen oxidase

Hereditary coproporphyria

Protoporphyrinogen oxidase

Variegate porphyria

Detects d-ALA and porphobilinogen

Ehrlich’s Rxn

Tests for uroporphyrin, coproporphyrin& protoporphyrin: violet/pink/red

Fluorescence at 550-600 nm

CDC-recommended test for Lead Poisoning

FEP

Accumulation of incompletely metabolized polysaccharide portions in the lysosome

MUCOPOLYSACCHARIDE DISORDERS

-mucopolysaccharidesaccumulate in the cornea; skeletal structure abnormality and severe mental retardation

HURLER

-skeletal structure abnormality and severe mental retardation

HUNTER

-mental retardation only

SANFILIPO

-cetyltrimethylammonium bromide test ==WHITE TURBIDITY

CTAB

-massive excretion of uric acid crystals in the urine caused by:-Failure to inherit gene to produce

LESCH-NYHAN DISEASE

:”orange sand” in diaper

PURINE DISORDERS

HYPOXANTINE GUANINE

PURINE DISORDERS

PHOSPHORIBOSYLTRANSFERASE

PURINE DISORDERS