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.