Diseases

Urea Cycle Disorders

Description: Urea Cycle Disorders are inherited genetic defects. Normally, the liver supplies six enzymes to metabolize the protein that we eat. In these disorders, the liver fails to produce enzymes necessary to metabolize protein. Instead, one of the enzymes is either partially produced, or not produced at all.

There are six enzyme disorders of the urea cycle namely: Carbamyl Phosphate Synthetase (CPS) deficiency, N-Acetulglutamate Synthetase (NAGS) deficiency, Ornithine Transcarbamylase (OTC) deficiency, Argininosuccinic Acid Synthetase (Citrullinemia/ AS) deficiency, Argininosuccinate Lyase (Argininosuccinic Aciduria/ AL/ASA) deficiency, and Arginase (AG) deficiency.

Effect: The protein builds up in the bloodstream as ammonia, causing irreversible brain damage, coma, and eventually death.

Treatment: The treatment of urea cycle disorders consists of reducing the amount of protein the child consumes, giving medication to take extra ammonia out of the body, and adding arginine or citrulline (according to the specific UCD being treated) to help the body use protein.

Arginosuccinate lyase deficiency

Longevity w/out meds:	adulthood
Prevalence:	Worldwide 1:70,000

Carbamoyl Phospate synthetase (CPS) deficiency

Longevity w/out meds:	lethal neonatal type 1-2 weeks Delayed onset type
Prevalence:	Worldwide unknown US 1:75,000 Japan 1:800,000

Ornithine Transcarbamylase (OTC) deficiency

Longevity w/out meds:	neonatal onset – die rapidly Late treated infants who survive may manifest developmental disabilities
Prevalence:	Worldwide 1:80:000

Citrullinemia

Longevity w/out meds:	longest survival of an untreated infant with classic citrullinemia type I is 17 days
Prevalence Worldwide:	Type I 1:57,000 Type II 1:100,000-230,000

Source: Mr. Jess G Thoene, MD
Active Emeritus Professor of Pediatrics
Director, Biochemical Genetics Laboratory
University of Michigan
Ann Arbor, MI
jthoene@umich.edu
http://www.ncbi.nlm.nih.gov