AUB - Inborn Error of Metabolism

Disorders

Enzyme Deficient / Cause

Substances which accumulate in Urine Phenylalanine Phenylacetic acid Phenylpyruvic acid

Phenylketonuria

Phenylalanine hydroxylase

Tyrosyluria/Tyrosinuria

ρ-hydroxyphenylpyruvic acid oxidase

Tyrosine ρ-hydroxyphenylpyruvic acid ρ-hydroxyphenyllactic acid

 Alkaptonuria  Alkaptonuria

Homogentistic Homogentistic acid oxidase

Homogentistic Homogentistic acid acid

Melanuria

Overproliferat ion of melaninproducing cells

Melanin

Maple Syrup Urine Disease (MSUD)

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

 Amino acids: acids: Valine, Leucine and Isoleucine

Isovaleryl CoA in the leucine pathway Error in the metabolic pathway

Isovalerylglycine

Converting isoleucine, valine, threonine and methionine to succinyl CoA

Methylmalonic acid Propionic acid

Organic acidemias:  A. Isovaleric Isovaleric academia academia

B. Propionic and Methylmalonic acidemias

Clinical Significance

Mental Retardation

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

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

Disorders

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

Excess amount of Serotonin

5-HIAA

Malignant tumors involving the Argentaffin cells in the intestines

Tryptophan Disorders:  A. Indicanuria Indicanuria

B. Disorder in the production of  5-Hydroxyindoleacetic acid

Cystine Disorders:  A. Cystinuria Cystinuria

Inability of renal tubules to reabsorb cystine filtered by the glomerulus

Cystine, lysine, arginine, ornithine

Formation of urinary calculi

B. Cystinosis

Inborn error in metabolism of  cystine but of unknown cause

Cystine

Fanconi’s Syndrome Cystine crystals deposits in many areas of the body; Inability to reabsorb amino acids, potassium, water, phosphorus and sugars

C. Homocystinuria

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

Homocystine and methionine

Mental retardation

Disorders

Enzyme Deficient / Cause

Porphyrin Disorders

Inherited as inborn error of  metabolism or Acquired through erythrocyctic and hepatic malfunctions caused either by metabolic disease or  exposure to toxic agents

Mucopolysaccharides Disorders

Inherited disorders in the metabolism of polysaccharides

Purine Disorders

Melituria

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

Clinical Significance

Porphyrias Lead Poisoning

Dermatan sulfate, keratin sulfate, Heparin sulfate

Sanfilippo’s Syndrome Hurler’s Syndrome Hunter’s Syndrome

Deficiency in enzyme hypoxanthine-guanine phosphoribosyl transferase

 Accumulation  Accumulation of of uric acid acid through out the body

Lesch-Nyhan Disease

Inherited Disorder

Urinary sugars

Majority do not cause metabolic disturbance