Effectiveness of carbohydrate-restricted diet and arginine granules therapy for adult-onset type II citrullinemia: a case report of siblings showing homozygous SLC25A13 mutation with and without the disease.

Case 1 is a 37-year-old Japanese man who was admitted to this hospital with a disturbance of consciousness. A diagnosis of adult-onset type II citrullinemia was made by DNA analysis of SLC25A13 (851del4/851del4) and measurement of hepatic ASS activity (2% of control value). After regaining consciousness, Case 1 was started on a dietary therapy, revealing that hypertriglyceridemia and ketogenesis impairment deteriorated on a low-protein diet and ameliorated on a carbohydrate-restricted (high-protein) diet. Case 1 could tolerate 70 g/day of protein while using arginine granules and developed hyperammonemia only after discontinuation of the administration. Case 2 (an elder brother of Case 1) is also homozygote for the same SLC25A13 mutation. The hepatic activity of argininosuccinate synthetase was about 20% of the control value. However, Case 2 exhibited neither hyperammonemia nor lipid metabolism abnormalities. These results suggest that, although adult-onset type II citrullinemia is caused by a deficiency of citrin, which plays key roles in carbohydrates, amino acids and even lipid metabolism, some other environmental or genetic factors are required for the onset of the disease, and from the authors' clinical experience, a carbohydrate-restricted (relatively high-protein) diet is advocated as a benefit to the patients, and that arginine granules are indispensable to this new dietary therapy.