Metabolic Diseases Flashcards
Phenylketonuria, including test
Causes severe mental retardation. Normal conversion of phenylalanine to tyrosine is disrupted after failure to inherit the gene to produce the enzyme phenylalanine hydroxylase. Also produces children with fair complexions—even in dark-skinned families—owing to the decreased production of tyrosine and its pigmentation metabolite melanin. As the child matures, alternative pathways of phenylalanine metabolism develop. Test for phenylpyruvic acid use a ferric chloride reaction that produces a permanent blue-green color.
Tyrosyluria
Inherited or acquired defect in Tyrosine metabolism, urine may contain excess tyrosine or its degradation products, p-hydroxyphenylpyruvic acid and p-hydroxyphenyllactic acid. Seen in premature infants, with underdevelopment of the liver function required to produce the enzymes necessary to complete the tyrosine metabolism or acquired through severe liver disease. Tyrosine and leucine crystals may be observed.
Inherited Tyrosyluria (3 Types)
Type 1: caused by the deficiency of the enzyme fumarylacetoacetate hydrolase (FAH) and produces a generalized renal tubular disorder and progressive liver failure in infants soon after birth.
Type 2: tyrosinemia is caused by lack of the enzyme tyrosine aminotransferase. Develop corneal erosion and lesions on the palms, fingers, and soles of the feet caused by crystallization of tyrosine in the cells.
Type 3: tyrosinemia is caused by lack of the enzyme p-hydroxyphenylpyruvic acid dioxygenase. This can result in mental retardation if dietary restrictions of phenylalanine and tyrosine are not implemented
Alkaptonuria
Failure to inherit the gene to produce the enzyme homogentisic acid oxidase, causing homogentisic acid to accumulate in the blood, tissues, and urine.
Maple Syrup Urine Disease
Involves leucine, isoleucine, and valine. Transamination of the three amino acids in the liver to the keto acids (α-ketoisovaleric, α-ketoisocaproic, and α-keto-β-methylvaleric) occurs normally. The gene for the enzyme necessary for oxidative decarboxylation of these keto acids is not inherited, causing their accumulation in the blood and urine.
Tryptophan Disorders
Normally, Tryptophan in the gut is either reabsorbed for use by the body or is converted to indole and excreted.
In inherited disorders (including Hartnup Disease) increased amounts of tryptophan are converted to indole, reabsorbed and circulated to the liver, where it is converted to indican and then excreted in the urine.
Hartnup Disease
Hartnup disease affects not only the intestinal reabsorption of tryptophan but also the renal tubular reabsorption of other amino acids, resulting in a generalized aminoaciduria
5-Hydroxyindoleacetic Acid
Serotonin is produced from tryptophan by the argentaffin cells; when carcinoid tumors involving the argentaffin (enterochromaffin) cells develop, excess amounts of serotonin are produced, resulting in the elevation of urinary 5-HIAA levels. Adding nitrous acid and 1-nitroso-2-naphthol to urine that contains 5-HIAA causes the urine to turn purple to black.
Cystinuria
Inability of the renal tubules to reabsorb cystine filtered by the glomerulus. Because cystine is much less soluble than the other three amino acids, laboratory screening determinations are based on observing cystine crystals in the sediment of concentrated or first morning specimens.
Cystinosis
The disorder has two general categories, termed nephropathic and nonnephropathic, within these are three variations, ranging from a severe fatal disorder developed in infancy to a benign form appearing in adulthood. It creates crystalline deposits of cystine in many areas of the body, including the cornea, bone marrow, lymph nodes, and internal organs. The proximal convoluted tubules are affected by the cystine deposits which interfere with reabsorption
Homocystinuria
Defects in the metabolism of the amino acid methionine produce an increase in homocystine. An additional screening test for homocystinuria must be performed by following a positive cyanide-nitroprusside test result with a silver-nitroprusside test, in which only homocystine will react.
Poryphyrin Disorders
ALA, porphobilinogen, and uroporphyrin are the most soluble - appear in the urine.
Classified by their clinical symptoms, either neurologic/psychiatric or cutaneous photosensitivity or a combination of both.
The two screening tests for porphyrinuria use the Ehrlich reaction and fluorescence under ultraviolet light. Acetyl acetone must be added to the specimen to convert the ALA to porphobilinogen prior to performing the Ehrlich test, it can only be used to find these two substances.
Fluorescent screening for the other porphyrins uses their extraction into a mixture of glacial acetic acid and ethyl acetate. Positive reactions fluoresce as violet, pink, or red, depending on porphyrin concentration.
Lesch-Nyhan Disease
Inherited as a sex-linked recessive results in massive excretion of urinary uric acid crystals. Failure to inherit the gene to produce the enzyme hypoxanthine guanine phosphoribosyltransferase is responsible for the accumulation of uric acid throughout the body.
