Table 1.

Genetic and Clinical Findings in Individuals with GTPBP3 Mutations

ID	Sex	GTPBP3 Mutations	OXPHOS Activities in Skeletal Muscle				Clinical Features
		cDNA (NM_032620.3) and Protein (NP_116009.2)	RCC	% of Lower Control Range	Absolute Values	Reference Range	AO	Course	HCM	Histochemical COX Defect	Other Features
#49665a,b	male	c.[1291dupC; 1375G>A], p.[Pro430Argfs∗86; Glu459Lys]	I	15%	0.025	0.17–0.56	10 years	alive 14 years	yes	ND	consanguineous parents (1st cousins), mild intellectual disability, fatigability, limited vision, lactic acidosis
			II	ND	ND	ND
			II+III	normal	0.201	0.08–0.48
			IV	24%	0.267	1.1–5.0
#36349b	male	c.[1291dupC; 1375G>A], p.[Pro430Argfs∗86; Glu459Lys]	I	no data	no data	no data	no data	alive 17 years	no data	no data	sibling of #49665 with similar clinical symptoms
			II
			II+III
			IV
#66143a	male	c.[476A>T; 964G>C], p.[Glu159Val; Ala322Pro]	I	7%	0.01	0.19–0.48	2 years	alive 5 y ears	yes	ND	unrelated parents, sudden respiratory failure, lactic acidosis
			II	normal	0.10	0.07–0.12
			II+III	normal	0.12	0.09–0.22
			IV	28%	0.12	0.44–0.92
#72425a	female	c.[484G>C; 673G>A; 964G>C], p.[Ala162Pro; Glu225Lys; Ala322Pro]	I	14%	0.015	0.11–0.30	3.5 months	died 8 months	DCM	yes	unrelated parents, cyanosis, hyporeactivity, DCM with residual ejection fraction of 20%, lactic acidosis
			II	normal	0.21	0.12–0.25
			II+III	normal	0.06	0.006–0.14
			IV	45%	0.76	1.7–4.0
#75191a	female	c.[1009G>C; 1009G>C], p.[Asp337His; Asp337His]	I	31%	0.03	0.10–0.25	birth	died 1 day	yes	yes	unrelated parents, Kussmaul breathing, stridor, hypotonic, hyporeactivity, RVH, lactid acidosis
			II	normal	0.16	0.14–0.25
			II+III	normal	0.12	0.13–0.25
			IV	15%	0.09	0.60–1.48
#76671	male	c.[665−2delA; 665−2delA], p.[Ala222Gly; Asp223_Ser270del; Ala222Gly; Asp223_Ser270del]	I	45%	0.05	0.11–0.30	birth	died 10 months	yes	yes	unrelated parents, hypotonia from birth, RVH, WPW, lactic acidosis
			II	normal	0.16	0.12–0.25
			II+III	ND	ND	0.06–0.14
			IV	17%	0.29	1.7–4.0
#81471a	male	c.[424G>A; 424G>A], p.[Glu142Lys; Glu142Lys]	I	12%	0.012	0.104 ± 0.036	4 weeks	died 5 weeks	yes	yes	consanguineous parents, two healthy siblings, one miscarriage, FTT, poor weight gain and feeding, concentric LVH, lactic acidosis
			II	normal	0.098	0.145 ± 0.047
			II+III	normal	0.850	0.544 ± 0.345
			IV	17%	0.127	1.124 ± 0.511
#75168a	female	c.[770C>A; 770C>A], p.[Pro257His; Pro257His]	I	normal	no data	no data	2 years	alive 5 years	no	ND	consanguineous parents (1st cousins), developmental delay, epileptic seizures, intellectual disability, MRI hyperintense lesions of basal ganglia typical to Leigh syndrome, lactic acidosis
			II	normal
			II+III	normal
			IV	normal
#82790a	female	c.[8G>T; 934_957del], p.[Arg3Leu; Gly312_Val319del]	I	36%	0.107	0.301 ± 0.05	1 year	alive 2 years	no	ND	unrelated parents, seizures, severe hypotonia, developmental delay, lactic acidosis
			II	normal	0.424	0.272 ± 0.05
			II+III	normal	0.21	0.25 ± 0.093
			IV	21%	0.008	0.035 ± 0.011
#83904a,c	female	c.[32_33delinsGTG; 32_33delinsGTG], p.[Gln11Argfs∗98; Gln11Argfs∗98]	I	64%	4.2	6.5–17	1 week	died 9 months	yes	ND	consanguineous parents (1st cousins), lactic acidosis, WPW
			II	normal	16.1	13.6–45.7
			II+III	normal	5.8	4.3–13.2
			IV	25%	9.9	74–294
#83905a,c	female	c.[32_33delinsGTG; 32_33delinsGTG], p.[Gln11Argfs∗98; Gln11Argfs∗98]	I	no data	no data	no data	birth	died 10 days	yes	ND	consanguineous parents (1st cousins), lactic acidosis, WPW
			II
			II+III
			IV
#66654a	female	c.[673G>A; 964G>A]; [=] p.[Glu255Lys; Ala322Pro]; [=]	I	64%	0.09	0.14–0.35	1.5 months	alive	no	ND	intrauterine growth retardation, lactic acidosis, leukodystrophy, generalized hypotonia
			II	normal	0.19	0.18–0.41
			II+III	90%	0.27	0.30–0.67
			IV	normal	1.42	0.42–1.26

Abbreviations are as follows: AO, age of onset; HCM, hypertrophic cardiomyopathy; DCM, dilated cardiomyopathy; FTT, failure to thrive; LVH/RVH, left/right ventricular hypertrophy; ND, not determined; WPW, Wolff-Parkinson-White syndrome.

Mitochondrial respiratory chain complexes (RCC) in muscle: I, NADH:CoQ-oxidoreductase; II, succinate:CoQ-oxidoreductase; II+III, succinate:cytochrome c reductase; IV, cytochrome c oxidase (COX).

Enzyme activities were determined in muscle biopsies and normalized to citrate synthase (CS). Absolute values and reference ranges are given in [mU / mU CS].

^aInvestigated by exome sequencing.

^b,cThese individuals are siblings.