Case 3
This patient is a boy, born at term after uneventful pregnancy and
delivery. His parents declared non-consanguinity. The boy’s development
was normal, although he presented aversion to meat and dairy. At the age
of eight years, after a week of dairy-rich diet, he presented to a
hospital with symptoms of gastroenteritis, balance problems and
qualitative disturbances of consciousness. CNS infection and brain tumor
were ruled out and further diagnostic tests revealed rapidly increasing
hyperammonemia (198 µmol/L, followed by 281 µmol/L; normal
<60), with high concentrations of glutamine in the serum and
CSF (1173 µmol/L and 3033 µmol/L, respectively; normal ranges 152 – 700
and 365 – 700), low citrulline concentrations (11.1 µmol/L in serum and
3.6 µmol/L in CSF; normal ranges 1 – 55 and 0 – 8, respectively),
normal serum but decreased CSF arginine concentrations (30.9 µmol/L and
13.4 µmol/L, respectively; normal ranges 6 – 187 and 14.2 – 25.8) and
normal ornithine concentrations (12.8 µmol/L in serum and 16.9 µmol/L in
CSF). Urinary organic acids revealed elevated orotic acid (9.5 mmol/mol
creatinine; normal range 0.08 – 1.08). The treatment with
hemodiafiltration was started immediately but the ammonia level remained
high (291 µmol/L) and the patient’s neurologic status worsened.
Administration of sodium benzoate, sodium phenylbutyrate and NCG led to
decrease of ammonia concentration to normal levels (< 60
µmol/L) within hours and patient status improved rapidly. Biochemical
tests done on the third day of treatment revealed almost normal serum
glutamine concentration (530 µmol/L) and normal level of orotic acid
(4.80 mmol/mol creatinine). The low protein diet was implemented, but
the patient still required high doses of sodium benzoate, L-arginine
(initially intravenously and then orally) and hypercaloric diet to keep
ammonia at acceptable levels (70 - 100 µmol/L). Because laboratory
investigations and quick response to treatment with sodium benzoate,
sodium phenylbutyrate and NCG suggested NAGSD, therapeutic trial with
NCG at a dose of 100 mg/kg was performed after withdrawal of ammonia
scavengers. Ammonia normalized rapidly from 120 µmol/L to 44 µmol/L
after administration of NCG. Following the start of treatment with NCG
at a dose of 15 mg/kg, the patient had no hyperammonemic episodes and is
doing well clinically, although he still prefers low-protein diet.