Zebra Cards > Samples > DI-005 


    Card DI-005
In a woman, severe headaches after eating meat
Back of Card DI-005
Differential Diagnosis
  • ornithine transcarbamylase (OTC) deficiency
    (McKusick 31125)


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 retardation.1

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 women.

(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.
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©1986-2000 John Sotos, MD. All rights reserved.

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