AUBF PART 2

Benedict test / Silver nitrate test

Urine test for Alkaptonuria

Ferric chloride test

Urine test for Alkaptonuria, MSUD, Melanuria, PKU

Hoesch test / Watson-Schwartz test

Urine test for Porphyria

Nitrosonaphthol test

Urine test for Tyrosinuria

PTAMO CPMGL

1. Phenylketonuria

2. Tyrosinemia

3. Alkaptonuria

4. MSUD

5. Organic acidemias

6. Cystinosis

7. Porphyria

8. Mucopolysaccharidoses

9. Galactosemia

10. Lesch-Nyhan disease

Overflow inherited metabolic disorders

IMI 5P

1. Infantile tyrosinemia

2. Melanuria

3. Indicanuria

4. 5-hydroxyindoleacetic acid

5. Porphyria

Metabolic disorders of urine

HC

Hartnup disease

Cystinuria

Renal related urine disorder

Phenylketonuria

Results in severe intellectual disability. Increased amounts of keto acids, including phenylpyruvate. Occurs when the normal conversion of phenylalanine to tyrosine is disrupted. Produces children with fair complexions and lighter hair and eyes even in dark skinned families due to the decreased production of tyrosine and its pigmentation metabolite melanin. Caused by failure to inherit the gene to produce the enzyme phenylalanine hydroxylase. Autosomal recessive trait.

Tyrosyluria

Accumulation of excess tyrosine in the plasma producing urinary overflow. Most frequently seen type is transitory which is caused by underdevelopment of the liver function required to produce the enzymes necessary to complete the tyrosine metabolism. Urine may contain excess tyrosine, p-hydroxyphenylpyruvic acid and p-hydroxyphenyllactic acid.

Type 1 Tyrosyluria

Caused by the deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). Produces a generalized renal tubular disorder and progressive liver failure in infants soon after birth. Diagnosed by the detection of tyrosine and succinylacetone in the urine and blood.

Type 2 tyrosinemia

Caused by lack of the enzyme tyrosine aminotransferase. Patients develop corneal erosions and lesions on the palms, fingers, and soles of the feet, believed to be caused by the crystallization of tyrosine in the cells. Patients may also have elevated 4-hydroxyphenylpyruvic acid in urine.

Type 3 tyrosinemia

Caused by lack of the enzyme p-hydroxyphenylpyruvic acid dioxygenase. Can result in intellectual disability, seizures, and intermitted ataxia if dietary restrictions of phenylalanine and tyrosine are not implemented. Diagnosed by the presence of elevated levels of plasma tyrosine and the presence of the urine metabolites 4-hydroxyphenylpyruvic acid, 4-hydroxyphenyllactic, and 4-hydroxyphenylacetic acid.

Melanuria

Increased urinary melanin. Indicates the prolifeeration of the normal melanin-producing cells, producing a malignant melanoma. These tumors secrete a colorless precursor of melanin, 5,6-dihydroxindole, which oxidizes to melanogen and then to melanin, producing the characteristic dark urine

Alkaptonuria

One of the six original IEMs described by Garrod. Third major defect in the phenylalanine-tyrosine pathway and occurs from failure to inherit the gene to produce the enzyme homogentisic acid oxidase. Brown stained or black stained cloth diapers and reddish stained diapers. Ochronosis, deposits in connective tissue, liver and cardiac diseases occur. Vitamin C is used because it hinders the accumulation and deposition of homogentisic acid.

Melanin

May react with sodium nitroferricyanide, producing a red color

Maple Syrup Urine Disease (MSUD)

Inherited as an autosomal recessive trait. Failure to inherit the gene for the enzyme necessary produce oxidative decarboxylation of a-ketoisovaleric, a-ketoisocaproic and a-keto-b-methylvaleric. Production of strong maple syrup odor caused by the rapid accumulation of keto acids in the urine. Treatment is restriction of dietary BCAAs.

2,4-dinitrophenylhydrazine test (DNPH)

Screening test for MSUD

Isovaleric acidemia

May be suspected when urine specimens, and sometimes the patient possess “sweaty feet” odor. This odor is caused by the accumulation of isovalerlyglycine due to a deficiency of isovaleryl coenzyme A in the pathway.

Propionic/Methylmalonic acidemias

Results from errors in the metabolic pathway converting isoleucine, valine, threonine, and methionine to succinyl coenzyme A.

Propionic acid

The immediate precursor to methylmalonic acid

Indicanuria

Also known as “Hartnup disease”. Causes increased amounts of tryptophan to be converted into indole. The excess indole is reabsorbed from the intestine into the blood stream and circulated to the liver, where it is converted to indican and then excreted in the urine.

5-Hydroxyindoleacetic Acid

Degradation product of Serotonin. Adding nitrous acid and 1-nitroso-2-naphthol to urine that contains it causes the urine to turn purple to black. Excretion of greater than 25mg/24h can be an indication of argentaffin cell tumors. Test is performed on a random or first morning specimen.

Cystinuria

Is marked by elevated amounts of the amino acid cystine in the urine. Due to the inability of the renal tubules to reabsorb cystine filtered by the glomerulus. Has two modes of inheritance where one in which reabsorption of all four amino acids (cystine, lysine, arginine, and ornithine) is affected, or one in which only cystine and lysine are not reabsorbed. Tested using cyanide-nitroprusside.

Cystinosis

Can range from a severe fatal disorder developed in infancy to a benign form appearing in adulthood. One can be nephropathic and non-nephropathic. Defect in the lysosomal membranes prevents the release of cystine into the cellular cytoplasm for metabolism. The incomplete metabolism of cystine results in crystalline deposits in many areas othe body. Fanconi syndrome also occurs. It

Homocystinuria

Defects in the metabolism of the amino acid methionine produces an increase in homocystein trhought the body. Increased levels results in failure to thrive, cataracts, intellectual disability, thromboembolic problems, stroke, and death. Gives a positive result with cyanide-nitroprusside test with a silver-nitroprusside test.

Porphyrins

Intermediate compounds in the productions of heme

Porphyrinuria

Observation of a red or port wine color to the urine after exposure to air. Uses Ehrlich reaction and fluorescence under UV in 550 to 600 nm range. Acetyl acetone must be added to convert ALA to porphobilinogen.

Hurler syndrome

Skeletal structure is abnormal and there is severe mental retardation. Mucopolysaccharides accumulate in the cornea of the eye. Inability of the renal tubules to reabsorb cystine filtered by the glomerulus. Treated by bone marrow transplants and gene replacement therapy.

Hunter syndrome.

Skeletal structure is abnormal and there is severe mental retardation. Mucopolysaccharides accumulate in the cornea of the eye. Defect in the lysosomal membranes.

Sanfilippo syndrome

Mental retardation. Defect in methionine metabolism.

Lesch-Nyan disease

Inherited as sex-linked recessive results in massive excretion of urinary uric acid crystals. Failure to inherit the gene to produce the enzyme hypoxanthine guanine phosphoribosyltransferase and is responsible for the accumulation of uric acid throughout the body. Patients suffer from severe motor defects, intellectual disability, a tendency towards self-destruction, gout, and renal calculi.

Galactosuria

Indicates the inability to properly metabolize galactose to glucose. Results in infant failure to thrive combined with liver disorders, cataracts, and severe intellectual disability.