Citrullinemia Type I


Citrullinemia Type I, (Argininosuccinate Synthetase Deficiency, Citrullinuria, Citrullinemia, ASS) is an autosomal recessive urea cycle disorder that causes ammonia and other toxic substances to accumulate in the blood. Two forms of citrullinemia have been described, both having different signs and symptoms, and are caused by mutations in different genes. Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions that takes place in the liver. These reactions process excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. Citrullinemia Type I is an autosomal recessive disease caused by mutation in the ASS gene which codes for argininosuccinate synthetase. A deficiency in this enzyme results in accumulation of citruilline as well as glycine and orotic acid in urine. Infants appear normal at birth, but within the first week of life symptoms such as feeding difficulties, irritability, hypotonia, seizures, and vomiting present and eventually lead to premature death.

Pathway legend Zoom in

Pathway Image

Pathway legend Zoom in

References

  1. eMedicine: Article 942435
  2. OMIM: Entry 215700
  3. Uniprot: P00966
  4. Walser, M. Urea cycle disorders and other hereditary hyperammonemic syndromes. (1983). Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S.; Goldstein, J. L.; Brown, M. S. The Metabolic Basis of Inherited Disease. (pp 402-483) (5th ed). New York: McGraw-Hill.
  5. Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. (2007). Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (pp 35) (2nd ed). Heilbronn: SPS Verlagsgesellschaft
  6. MCMURRAY WC, RATHBUN JC, MOHYUDDIN F, KOEGLER SJ: CITRULLINURIA. Pediatrics. 1963 Sep;32:347-57. Pubmed
  7. Northrup H, Lathrop M, Lu SY, Daiger SP, Beaudet AL, O’Brien WE: Multilocus linkage analysis with the human argininosuccinate synthetase gene. Genomics. 1989 Oct;5(3):442-4. Pubmed
  8. Saheki T, Ueda A, Hosoya M, Kusumi K, Takada S, Tsuda M, Katsunuma T: Qualitative and quantitative abnormalities of argininosuccinate synthetase in citrullinemia. Clin Chim Acta. 1981 Feb 5;109(3):325-35. Pubmed