We report a 41-year-old male of
citrullinemia associated with argininosuccinate
acid synthetase deficiency. He was admitted to the Hitachi General Hospital because of finger
tremor,
restlessness and
urinary incontinence. He had short stature and a poor appetite. Laboratory evaluation was summarized as follows: mild
hypoglycemia, low plasma
cortisol levels, delayed response of 17-OHCS and 17-KS to
ACTH administration in urine, and delayed response of plasma
ACTH level to
insulin administration. In this case,
ACTH deficiency is estimated to be a dysfunction of the hypothalamus. Replacement
therapy of
hydrocortisone improved his symptoms. He was readmitted to the hospital because of
delirium and
confusion, two weeks after the
hydrocortisone administration. At that time, he had flapping
tremor. Laboratory examination revealed
hyperammonemia (NH3: 231 micrograms/dl) and mild elevation of GOT and GPT. Serum and urinary
amino acid determination showed marked elevation of
citrulline (478.1 nmol/ml in serum, 4681.2 mumol/day in urine).
Lactulose administration,
low protein diet and
plasmapheresis were started, but he went into a
coma. Without any improvement, he died on the 29th hospital day. Autopsy examination of the liver disclosed fatty change. Adrenal cortex depicted severe
atrophy. Biochemical analysis of
urea cycle
enzymes of the liver and kidney showed decreased activity of
argininosuccinate synthetase (liver: 0.0022 U/mg
protein, 5% of that normal liver, kidney: 0.003 IU/mg
protein, 20% of that in normal kidney).
Citrullinemia associated with
ACTH deficiency have not reported in the literature. It may be presumed that
ACTH deficiency is concerned with the delayed onset of
hyperammonemia. The relation between
citrullinemia and endocrinological abnormalities is also discussed.