Rinsho Shinkeigaku (Clinical Neurology)

Case Report

A case of late-onset carbamoyl phosphate synthetase I deficiency, presenting periodic psychotic episodes coinciding with menstrual periods

Yosuke Wakutani, M. D. 1) , Hiroyuki Nakayasu, M. D. 1) , Takao Takeshima, M. D. 1) , Nozomi Mori, M. D. 1) , Keiko Kobayashi, M. D. 3) , Fumio Endo, M. D. 3) and Kenji Nakashima, M. D. 1)

1)Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University
2)Department of Pediatrics, Kumamoto University School of Medicine
3)Department of Biochemistry, Faculty of Medicine, Kagoshima University

Carbamoyl phosphate synthetase I deficiency (CPSID) is a rare metabolic disorder affecting the first enzymatic step of urea cycle. We report clinical manifestations of a female case of late-onset CPSID in Japan.
An 18-year-old girl was admitted to emergency room due to acute comatose state. Her parents had no apparent consanguineous history. She had suffered from intermittent psychotic episodes (excitation, aggressive behavior and insomnia) with nausea and vomiting from the age of 13, mostly coinciding with menstrual period. She had minor learning disability without major neurological deficits and convulsions. Her mental status was estimated as normal in her intermenstrual period. She had been diagnosed as having hysteria and premenstrual syndrome.
Her neurological findings on admission showed deep coma and hypotonic tetraparesis. Plasma ammonia level was markedly elevated (684 μ g/dl) without significant liver dysfunction. Blood urea nitrogen decreased to 6mg/dl. Continuous venovenous filtration with subsequencial administration of sodium benzoate and l-arginine was started to eliminate blood ammonia. Although the plasma ammonia level decreased to 300 μ /dl in next 10 hours, severe cerebral edema was observed in head computed tomography subsequently, followed by marked cerebral atrophy. Finally, her consciousness status became almost alert a month after the onset, but her mental status was severely retarded. CPSI activity of her biopsied liver markedly decreased and she was diagnosed as having CPS ID. CPSI cDNA analysis of her biopsied liver demonstrated a V1149G mutation. Genomic DNA analysis showed that she was heterozygous in V1149G mutation. The mutation allele was derived from her father. The causative factor for absence or very low level of maternal CPSI mRNA will require further analysis.

(CLINICA NEUROL, 41: 780－785, 2001)
key words: carbamoyl phosphate synthetase I deficiency, late-onset, psychotic episodes, menstrual cycle

(Received: 12-Sep-01)