- ornithine transcarbamylase (OTC) deficiency
OTC, a hepatic enzyme of the urea cycle, catalyzes the formation of citrulline
from carbamyl phosphate and ornithine. Deficiency of OTC, an X-linked trait,
results in hyperammonemia.1
Affected males have no OTC activity and die in
the neonatal period.2
In [heterozygous] females, however, random inactivation
of affected X chromosomes (the Lyon phenomenon) results in some
hepatocytes with normal OTC activity. Owing to this mosaicism, symptoms in
females are variable, ranging from none to severe mental and physical
Formerly thought to appear by the end of the first decade of life or not at all,
onset of severe symptoms in the late 30s was recently reported in two women.1
In each case, superimposed liver disease (due to alcohol and cytomegalovirus,
respectively) probably contributed to adult unmasking of OTC deficiency. One
also had a lifelong history of headaches precipitated by eating meat, as has been
reported several times in asymptomatic women with OTC deficiency. These
headaches may be labelled "migraine" because they are accompanied by nausea,
vomiting, and, occasionally, by neurologic signs. Catabolic stress (such as
surgery) or high protein/high nitrogen meals can precipitate the headaches.1,3
Thus, an aversion to high protein meals may develop early in life.1,4
(l) Ann Intern Med. 106:556-558 (1987). Nice discussion; case reports of two
(2) Exceptions: [a] New End J Med. 315:744-747 (1986). [b] New Engl J
Med. 319:999-1003 (1988).
(3) Interestingly, gout attacks are similarly provoked. [Scientific American
Medicine. 15:IX:4 (5/86).]
(4) Carriers of other urea cycle enzyme defects may have similar headaches.
[The Metabolic Basis of Inherited Disease. 5th ed. JB Stanbury et al (eds).
New York: McGraw-Hill (1983). p 414.]
Zebra Cards: An Aid to Obscure Diagnoses. JG Sotos. Philadephia: American College of Physicians, 1989. ISBN 0-943126-13-4. Copyright © 1989 American College of Physicians. All Rights Reserved. Phone: 1-800-523-1546.