Suggested guidelines for the diagnosis and management of urea cycle disorders

Table 8 Dosages of peroral drugs for long-term treatment of UCDs

Disorder	Sodium benzoate^a	Sodium PBA^a,b	L-Arginine^a (hydrochloride or free base)	L-Citrulline^a	Carbamyl- glutamate^a
NAGSD	–	–	–	–	10–100 mg/kg/d
CPS1D	≤ 250mg/kg/d^c,d maximum: 12g/d	<20 kg: ≤250mg/kg/d^c,d >20 kg: 5g/m2/d maximum: 12g/day	<20 kg: 100-200mg/kg/d^c(0.5-1mmol/kg/d) >20 kg: 2.5-6g/m2/d maximum: 6g/d	100-200mg/kg/d^e maximum: 6g/d	–
OTCD	same	same	same	same	–
ASSD	same	same	<20 kg: 100-300mg/kg/d^c,d>20 kg: 2.5-6g/m2/d maximum: 6g/d	–	–
ASLD	same	–	same	–	–
ARG1D	same	same	–	–	–
HHH syndrome	same	same	<20 kg: 100-200mg/kg/d^c >20 kg: 2.5-6g/m2/d maximum: 6g/d	same	–

All medications should be divided into three to four equal daily doses taken with meals and distributed as far as possible throughout the day. Grade of recommendation, C-D.
^a100 mg of each drug correspond to the following amounts in mmols: 0.694 sodium benzoate; 0.537 sodium PBA; 0.475 arginine hydrochloride; 0.574 arginine base; 0.571 citrulline; 0.532 carbamylglutamate.
^b Sodium PBA was considered of second choice for long-term treatment by most guideline group members. It should be given together with sodium benzoate in patients in which benzoate alone is not enough.
^c Serum/plasma levels of benzoate/PBA and plasma levels of arginine (aim are fasting levels of 70–120 μmol/L) should be monitored to adjust dosages and in case of high or repeated doses.
^d In some patients higher doses are needed, according to expert advice. For PBA, FDA and EMA approved doses are 450-600mg/kg/d in children of <20kg, and, above 20 kg bw, 9.9-13 g/m²/d.
^e Citrulline may be preferable. When given no need for concomitant use of L-arginine.

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