Mutation Study of Malaysian Patients with Ornithine Transcarbamylase Deficiency: Clinical, Molecular, and Bioinformatics Analyses of Two Novel Missense Mutations of the OTC Gene

Table 1

Summary of clinical and molecular findings of 16 patients with OTC deficiency.

Patient	Sex	First acute episode					Subsequent clinical progress	Family history
		Age	Presenting symptoms	Blood ammonia (first measurement - maximum value, μmol/l, N.R. 50–80)	Therapy received	Outcome
1	M	3d	Poor suck, reduced oral intake and lethargy progressing to coma	350 -780	Stop protein intake, PFN, SB, SPB, L-Arg, PD, MV	Survived	Spastic tetraplegia, severe psychomotor retardation, frequent hyperammonemic episodes despite a low-protein diet and treatment with oral ammonia scavengers, fatal encephalopathy at 6 y	Negative
2	F	6y	Recurrent vomiting, difficulty in breathing following a febrile illness	215 - 310	iv SB, SPB, L-Arg,	Survived	Mild learning disability, infrequent decompensation on a low-protein diet and oral ammonia scavengers	A younger male sibling died of hyperammonemic coma at 40d
3	M	2d	Poor feeding, lethargy, tachypnea, irritability, coma	305 - 850	Stop protein intake, PFN, PD, MV	Died	-	Negative
4	F	7d	Feeding intolerance, irritability, altered sensorium	250 - 480	Stop protein intake, PFN, SB, SPB, L-Arg, PD, MV	Survived	Moderate developmental delay/learning disability, recurrent decompensation	Negative
5	M	5d	Sudden onset of fits, progressing to somnolence and coma and respiratory arrest	450 – 2,361	Stop protein intake, PFN, MV	Died	-	A male sibling died suddenly during neonatal period (undiagnosed)
6	M	2d	Feeding refusal, vomiting, lethargy, progressing to coma	750 - 865	Stop protein intake, PFN, MV	Died	-	Negative
7	M	3d	Poor suck, lethargy, hypotonia, coma	345 – 2,915	Stop protein intake, PFN, PD, MV	Died	-	Negative
8	F	1y	History of failure to thrive, hypotonia, seizures. Acute encephalopathy and respiratory distress following a febrile illness.	236 - 560	Stop protein intake, PFN, phenytoin, MV	Died	-	Multiple neonatal deaths among maternal male siblings
9	M	5d	Vomiting, lethargy, seizures, progressing to coma	201 - 990	Stop protein intake, PFN, SB, SPB, L-Arg, PD, MV	Died	-	Negative
10	M	2d	Poor suck, vomiting, progressive lethargy, and irritability	320 - 980	Stop protein intake, PFN, MV	Died	-	Negative
11	M	2d	Lethargy, poor breathing effort, progressing to cardiorespiratory collapse	1,700	Stop protein intake, PFN, MV	Died	-	Multiple neonatal deaths among maternal male siblings
12	M	2d	Poor oral intake and lethargy progressing to coma	468 - 789	Stop protein intake, PFN, SB, SPB, L-Arg, PD, MV	Survived	Severe psychomotor retardation, frequent hyperammonemic episodes despite a low-protein diet and treatment with oral ammonia scavengers, fatal encephalopathy at 2y	Negative
13	M	2d	Reduced oral intake, lethargy, irritability, progressing to coma	248 – 1,065	Stop protein intake, PFN, SB, SPB, L-Arg, CVVH, MV	Survived	Mild psychomotor retardation, infrequent hyperammonemic episodes on low-protein diet and oral ammonia scavengers	Negative
14	M	2d	Poor suck, lethargy, abnormal breathing, progressing to coma	332 - 976	Stop protein intake, PFN, SB, SPB, L-Arg, MV	Died	-	First one diagnosed in the family
15	F	14y	Vomiting, seizures and progressive acute encephalopathy following a febrile illness	Not done	PFN, phenytoin, antibiotics, MV	Died	-	Sibling of Patient 14 (They presented around the same time.)
16	F	34y	History of protein avoidance. Post-partum delirium	180 - 250	Stop protein intake, PFN, high calories intake, SB, SPB, L-Arg	Survived	Mildly symptomatic. Nausea if consuming high protein content foods	Mother of Patients 14 and 15

M: male, F: female, y: years, d: days, PFN: parenteral fluid and nutrition, L-Arg: L-arginine, SB: sodium benzoate, SPB: sodium phenylbutyrate, PD: peritoneal dialysis, CVVH: continuous venovenous hemodiafiltration, and MV: mechanical ventilation.