Disorders Phenylketonuria

Enzyme Deficient / Cause Phenylalanine hydroxylase

Substances which accumulate in Urine Phenylalanine Phenylacetic acid Phenylpyruvic acid Tyrosine -hydroxyphenylpyruvic acid -hydroxyphenyllactic acid

Clinical Significance Mental Retardation

Tyrosyluria/Tyrosinuria

-hydroxyphenylpyruvic acid oxidase

Transitory Tyrosinemia Hereditary Tyrosinemia associated w/ liver and renal disorders Dark blue to black pigmentation of cartilage & connective tissues Liver & Cardiac disorders Malignant melanoma

Alkaptonuria

Homogentistic acid oxidase

Homogentistic acid

Melanuria

Overproliferation of melaninproducing cells Decarboxylases and other enzymes necessary for conversion of keto amino acids to fatty acids

Melanin

Maple Syrup Urine Disease (MSUD)

Amino acids: Valine, Leucine and Isoleucine

Elevated plasma keto acids Symptoms: Neonatal vomiting, seizure and stupor, often episodes of hypoglycemia Organic acidemias Symptoms: Early severe illness, vomiting, Metabolic acidosis, hypoglycemia, increased serum ammonia, Ketonuria

Organic acidemias: A. Isovaleric academia

Isovaleryl CoA in the leucine pathway Error in the metabolic pathway Converting isoleucine, valine, threonine and methionine to succinyl CoA

Isovalerylglycine

B. Propionic and Methylmalonic acidemias

Methylmalonic acid Propionic acid

Disorders Tryptophan Disorders: A. Indicanuria

Enzyme Deficient / Cause

Substances which accumulate in Urine

Clinical Significance

Increased amount of tryptophan which is converted to indole then to indicant and excreted in urine

Indican

Malabsorption syndrome, gastric cancer, intestinal obstruction, diseases of the stomach, presence of abnormal intestinal bacteria, Hartnup Disease Malignant tumors involving the Argentaffin cells in the intestines

B. Disorder in the production of 5-Hydroxyindoleacetic acid

Excess amount of Serotonin

5-HIAA

Cystine Disorders: A. Cystinuria Inability of renal tubules to reabsorb cystine filtered by the glomerulus Inborn error in metabolism of cystine but of unknown cause Cystine, lysine, arginine, ornithine Formation of urinary calculi

B. Cystinosis

Cystine

Fanconis Syndrome Cystine crystals deposits in many areas of the body; Inability to reabsorb amino acids, potassium, water, phosphorus and sugars Mental retardation

C. Homocystinuria

Defect in the metabolism of homocystine due to deficiency of enzyme cystathionine synthase

Homocystine and methionine

Disorders Porphyrin Disorders

Enzyme Deficient / Cause Inherited as inborn error of metabolism or Acquired through erythrocyctic and hepatic malfunctions caused either by metabolic disease or exposure to toxic agents Inherited disorders in the metabolism of polysaccharides

Substances which accumulate in Urine Porphobilinogen, aminolevulinic acid, coproporphyrin, uroporphyrin, protoporphyrin

Clinical Significance Porphyrias Lead Poisoning

Mucopolysaccharides Disorders

Dermatan sulfate, keratin sulfate, Heparin sulfate

Sanfilippos Syndrome Hurlers Syndrome Hunters Syndrome Lesch-Nyhan Disease

Purine Disorders

Deficiency in enzyme hypoxanthine-guanine phosphoribosyl transferase Inherited Disorder

Accumulation of uric acid through out the body

Melituria

Urinary sugars

Majority do not cause metabolic disturbance