Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1

Table 1

Summary of clinical and molecular characteristics of seven Malaysian patients with GA1.

Patient	1	2	3	4	5	6	7
Gender	Male	Male	Male	Male	Female	Female	Female
Race	Chinese	Chinese	Chinese	Chinese	Malay	Malay	Malay
Parental consanguinity	−	−	−	−	+	−	+
Age at onset	5 m	3 m	5 m	3 m	3 m	5 m	11 m
Age at diagnosis	6 y	13 y	8 m	7 m	5 y	6 m	2 y
Actual age	20 y	23 y	Died at 11 y	4 y	14 y	20 m	2 y
Findings at onset	Macrocephaly, seizures, irritable, dystonia, SDH	Macrocephaly, seizure, irritable, dystonia, SDE, hydrocephalus	Macrocephaly, neuroregression, SDH	Macrocephaly, SDH	Macrocephaly, SDH	Macrocephaly, seizure, irritable, dystonia, SDH	Macrocephaly, neuroregression, SDH
Precipitating illness	−	−	+	−	−	−	+
Dystonia	+	+	+	+	+	+	−
Motor disability	Severe	Severe	Severe	Severe	Moderate	Severe	Mild
Speech	Absent	Absent	Absent	Absent	Nearly fluent	Absent	Nearly fluent
CT/MRI brain findings	Typical	Typical, hydrocephalus	Typical	Typical, abnormal signal at putamen, cerebral atrophy	Typical, generalized cerebral atrophy	Typical	Generalized cerebral atrophy
Urine GA excretion	Increase	Increase	Increase	Increase	Increase	Increase	Increase
C5DC in DBS (ref. <0.22 mol/L)	ND	0.38	ND	ND	0.34	0.43	4.9
Nucleotide change	(1) c.892 G>A; (2) c.1244-2A>C	(1) c.1060G>A; (2) c.1168G>T	(1) c.1063 C>T; (2) c.1261 G>A	(1) c.382 C> T; (2) c.1063C>T	(1) c.227A>C; (2) c.227A>C	(1) c.392A>T; (2) c.1244-2A>C	(1) c.1157G>A; (2) c.1157G>A
Protein change	p.Ala298Thr; Splice site	p.Gly354Ser; p.Gly390Trp	p.Arg355Cys; p.Ala421Thr	p.Arg128; p.Arg355Cys	p.Gln76Pro; p.Gln76Pro	p.Glu131Val; Splice site	p.Arg386Gln; p.Arg386Gln
Reference	Goodman et al. (1998) [12]; Tang et al. (2000) [10]	Schwartz et al. (1998) [13]; This study	Goodman et al. (1998) [12]; Goodman et al. (1998) [12]	Busquets et al. [14]; Goodman et al. (1998) [12]	This study	This study; Tang et al. (2000) [10]	Goodman et al. (1998) [12]
Pathogenicity prediction (MutationTaster2)	Disease causing (both)	Disease causing (both)	Disease causing (both)	Disease causing (both)	Disease causing	Disease causing (both)	Disease causing

“+” = present; “−” = absent; SDH = subdural haemorrhage; SDE = subdural effusion; GA = glutaric acids; ND = not determined; and Typical = bilateral widening of the Sylvian fissures and atrophy over the frontotemporal regions.
Bold denotes novel mutation.