AUB - Urine Screening for Metabolic Disorders

URINE SCREENING FOR METABOLIC DISORDERS Overflow  The kidney is normal  Metabolic substances accumulate in blood and excreted in urine.  This is due to inherited disorders brought about by failure to inherit the gene which will determine the production of enzymes necessary for the normal metabolism of substances like CHON and CHO Renal 

There is an inability of the kidney to reabsorb constituents that is essential for the body’s equilibrium.

AMINO ACID DISORDERS

Urinary Melanin 

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ALKAPTONURIA     

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First identified in Norway in 1934 by Ivan Følling. most well known of the aminoacidurias. can cause SEVERE mental retardation if left undetected. it is caused by failure to inherit the gene to produce the enzyme phenylalanine hydroxylase. Urine characteristic is MOUSY ODOR sample.

Ferric Chloride Tube test – blue green 

is a nonspecific test that will react with many other amino acids and commonly ingested medications

2 MAJOR GROUPS OF DISORDERS MSUD • accumulation of one or more of the early amino acid degradation products

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Disorders of tyrosine metabolism may result from either inherited or metabolic defects. urine may contain excess tyrosine or its degradation products, p-hydroxyphenylpyruvic acid and phydroxyphenyllactic acid

Three types of Tyrosyluria/ Tyrosinemia Type I • Deficient in fumarylacetoacetate hydrolase enzyme. • Produces a generalized renal tubular disorder and progressive liver failure in infants soon after birth. Type II • caused by lack of the enzyme tyrosine aminotransferase. • Patients develop corneal erosion and lesions on the palms,fingers, and soles of the feet believed to be caused by crystallization of tyrosine in the cells Type III • lack of the enzyme p-hydroxyphenylpyruvic acid dioxygenase. • can result in mental retardation if dietary restrictions of phenylalanine and tyrosine are not implemented. MELANURIA Melanin  pigment responsible for the dark color of hair, skin, and eyes.  Deficient production of melanin= albinism

Organic Acidemia • accumulation of organic acids produced further down in the amino acid metabolic pathway.

MAPLE SYRUP URINE DISEASE (MSUD)   

TYROSYLURIA/ TYROSINEMIA 

one of the six original inborn errors of metabolism described by Garrod in 1902. ―alkali lover‖= ALKAPTONURIA urine from patients with this condition darkened after becoming alkaline from standing at room temperature 3rd major aminoacidura failure to inherit the gene at produce the enzyme homogentisic acid oxidase

BRANCHED-CHAIN AMINO ACID DISORDERS

PHENYLKETONURIA   

indicates the overproliferation of the normal melanin producing cells (melanocytes) producing a malignant melanoma. Produces 5,6,-hydorxyindole that will oxidize melanogen to melanin. Blackens urine upon exposure to air

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caused by an IEM Discovered in 1954 by Menke. There is accumulation of valine, isoleucine, leucine and their corresponding keto-acids that leads to encephalopathy and other progressive neurodegeneration if left untreated. Deficiency in decarboxylases and transaminases.

ORGANIC ACIDEMIA Isovaleric Acidemia • possess a characteristic odor of ―sweaty feet.‖ • caused by the accumulation of isovalerylglycine • deficiency in isovaleryl coenzyme Propionic Acidemia • result from errors in the metabolic pathway converting isoleucine, valine, threonine, and methionine to succinyl coenzyme A. Methylmalonic Acidemia • result from errors in the metabolic pathway converting isoleucine, valine, threonine, and methionine to succinyl coenzyme A.

TRYPTOPHAN DISORDERS INDICANURIA • •

increased amounts of tryptophan are converted to indole and then to indican then eventually excreted in urine. Seen in malabsorption, obstruction and in rare inherited disorder (Hartnup’s disease.)

5-HYDROXYINDOLEACETIC ACID (5-HIAA) •

Caused by excessive production of SEROTONIN, which results to elevated urinary 5-HIAA

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Normal daily excretion of 5-HIAA is 2-8 mg/ day. Increased production is seen in argentaffinoma. (>25 mg/day)

CYSTINE DISORDERS CYSTINURIA • • • • •

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Defect in the renal transport of amino acid. Characterized by marked by elevated amounts of the amino acid cystine in the urine. increased urinary cystine. Can cause renal calculi formations in early life. disorder has two modes of inheritance: reabsorption of all four amino acids—cystine, lysine, arginine, and ornithine—is affected cystine and lysine are not reabsorbed Sulfur odor of urine sample

Hurler’s Syndrome  skeletal structure is abnormal  there is severe mental retardation.  Accumulation of mucopolysaccharide eyes in the cornea of the eye Hunter’s Syndrome  skeletal structure is abnormal  there is severe mental retardation. Sanfilippo’s Syndrome  Can cause mental retardaton ONLY!

PURINE DISORDER LESCH-NYHAN DISEASE  

CYSTINOSIS • • • • •

Regarded as a genuine Inborn Error of Metabolism Has 2 general categories: Nephrotic cystinosis non-nephropathic cystinosis Presence of crystalline deposits of cystine crystals in different areas of body. (eyes, BM, lymph nodes) Fanconi’s syndrome also occurs. Sulfur odor of urine sample

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CARBOHYDRATE DISORDERS MELITURIA   

HOMOCYSTINURIA  

Due to the defect in methionine metabolism. increased homocystine can result in failure to thrive, cataracts, mental retardation, thromboembolic problems, and death

Porphyrias  disorders of porphyrin metabolism.  can be inherited or acquired from erythrocytic and hepatic malfunctions or exposure to toxic agents.  a common disease of early royalty in Europe as a result of intermarriage among the royals of different countries. PORPHYRINURIA   

observation of a red or port wine color to the urine after exposure to air. port wine urine color is more prevalent in the erythropoetic porphyrias. staining of the teeth may also occur.

MUCOPOLYSACCHARIDE DISORDERS MUCOPOLYSACCHARIDOSES Mucopolysaccharide   

Also known as glycosaminoglycans group of large compounds located primarily in the connective tissue. products most frequently found in the urine are dermatan sulfate, keratan sulfate, and heparan sulfate.

General term pertaining to increased urinary sugar. Inherited in nature. Does not cause any disturbance in body’s metabolism.

GALACTOSURIA 

PORPHYRIN DISORDERS Porphyrin  intermediate compounds in the production of heme.

An inherited disorder that is characterized by massive excretion of urinary URIC ACID Crystrals. Deficiency in hypoxanthine-guanine phosphoribosyl transferase. Patients suffer from severe motor defects, mental retardation tendency toward self- destruction, gout, and renal calculi

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Presence of galactose in urine that is due to inability of the body to metabolize galactose to glucose. Can be caused by the deficiency in any of the three enzymes:

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Galactose-1-phosphate uridyl transferase(GALT) Can cause the most severe and fatal symptoms associated with galactosuria

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Galactokinase Deficiency can cause cataract development in adulthood

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UDP-galactose-4-epimerase May be asymptomatic or can produce mild melaturic symptoms.

Other causes of Melituria LACTOSURIA 

may be seen during pregnancy and lactation.

FRUCTOSURIA 

associated with parenteral feeding and pentosuria with ingestion of large amounts of fruit.

SPECIAL SCREENING TESTS FOR URINE

15. Lesch-Nyhan Disease a. Determination of Uric Acid level in blood b. Microscopic Examination in Urine – increase in Uric Acid Crystals

1. Phenylketonuria a. Guthrie Test – growth of B. subtilis b. Phenistix – green gray c. 2,4 Dinitrophenylhydrazine – yellow d. Ferric Chloride Test Tube Test – blue green

16. Melituria a. Clinitest – orange red

2. Tyrosinemia a. Ferric Chloride Test Tube Test – transient green b. Phenistix – transient green c. 2,4 DNPH – yellow d. Nitroso-naphthol – red e. Microscopic Examination – tyrosine crystals are seen

COLOR    

Homogentistic Acid Melanin Indican Porphyrin

ODOR      

Phenylketonuria Maple Syrup Urine Disease Isovaleric Acidemia Cystinuria Cystinosis Homocystinuria

3. Alkaptonuria a. Ferric Chloride Test Tube Test – transient blue b. Silver Nitroprusside Test – black c. Clinitest – orange red 4. Melanuria a. Ferric Chloride Test Tube Test – gray black b. Acetest – purple c. Ehrlich’s Rxn – red 5. Maple Syrup Urine Disease a. Ferric Chloride Test Tube Test – green gray b. Nitroso-naphthol – red c. 2,4 DNPH – yellow d. Acetest – purple 6. Isovaleric and Propionic Acidemia a. 2,4 DNPH – yellow b. Acetest – purple 7. Mehtylmalonic Acidemia a. 2,4 DNPH – yellow b. Acetest – purple c. ρ-nitroaniline Test – emerald green 8. Indicanuria a. Ferric Chloride Test Tube Test – violet blue with chloroform 9. 5-Hyroxyindoleacetic Acid (5-HIAA) a. Ferric Chloride Test Tube Test – blue green b. Nitroso-naphthol – violet 10. Cystinuria a. Cyanide-nitroprusside – red purple 11. Cystinosis a. Cyanide-nitroprusside – red purple b. Clinitest – orange red 12. Homocystinuria a. Cyanide-nitroprusside – red purple b. Silver-nitroprusside – red purple 13. Porphyrinuria a. Ehrlich’s Rxn – red 14. Mucopolysaccharide Disorders a. Cetyltrimethylammonium bromide – white turbidity b. Metachromatic Staining Spot Test – blue spot

Abnormal Metabolic Constituent or Conditions Detected in Routine Urinalysis

CRYSTALS  Cystine  Leucine  Tyrosine  Lesch-Nyhan Disease Major Disorder and Carbohydrate Metabolism Associated with Abnormal Urinary Constituents Classified as to Functional Defect OVERFLOW Inherited  Phenylketonuria  Tyrosinemia  Alkaptonuria  Maple Syrup Urine Disease  Organic Acidemia  Cystinosis  Porphyria  Mucopolysaccharidoses  Melituria (Galactosuria)  Lesch-Nyhan Disease Metabolic  Tyrosinemia  Melanuria  Indicanuria  5-Hydroxyindoleacetic Acid  Porphyria Renal  

Hartnup Disease Cystinuria