Asymptomatic and late-onset ornithine transcarbamylase (OTC) deficiency in males of a five-generation family, caused by an A208T mutation

Clinical Genetics
O P van DiggelenE Bakker

Abstract

In a large five-generation Polish family, late-onset ornithine transcarbamylase (OTC) deficiency in males segregated with the missense mutation Ala208Thr (A208T), and all heterozygous females were asymptomatic. No other mutations were found in the coding sequences and intron-exon boundaries of the OTC gene. Surprisingly, the mutation originated from the great-grandfather of the index patient who died at age 59 of liver carcinoma. He never had dietary restrictions or hyperammonemic spells throughout life and appears to be the oldest male reported with OTC deficiency. The index patient had a severe OTC deficiency (3% of normal). Eight males died suddenly at ages 4 months to 23 years (average 14 years) after a foudroyant episode triggered by a common infection. The patients remained undiagnosed for 28 years because a metabolic defect was not considered to be the cause of the acute episodes. Recognition of the familial pattern of inheritance was initially unnoticed since the patients were admitted to eight different hospitals. DNA analysis predicted that two 'healthy' boys also had OTC deficiency, which was confirmed by abnormal results of allopurinol challenge tests. Initial suspicion of OTC deficiency in such families is complica...Continue Reading

References

Mar 1, 1979·The Journal of Clinical Endocrinology and Metabolism·I KriegerJ Roskamp
Dec 1, 1990·The Journal of Pediatrics·J E FinkelsteinS W Brusilow
Feb 1, 1988·Journal of Biochemistry·A HataI Matsuda
Nov 1, 1988·Archives of Disease in Childhood·E Drogari, J V Leonard
Feb 11, 1988·Nucleic Acids Research·S A MillerH F Polesky
Sep 18, 1986·The New England Journal of Medicine·E P DiMagnoJ D Jones
Feb 27, 1986·The New England Journal of Medicine·P C RoweS W Brusilow

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