Table 1.

Genetic and Clinical Findings in Sengers Individuals with AGK Mutations

ID	Sex	AGK Mutations Identified		Biochemical Investigations			Clinical Features
		cDNA (NM_018238.3)	Protein (NP_060708)	OXPHOS Defect	ATP Synthesis	Substrate Oxidation	AO	Course	CM	Cataract	Other Clinical Features	Literature
54027a	male	c.306C>T c.841C>T	p.Tyr102∗ p.Arg281∗	I, II+III, and V	impaired	impaired	1 weeks	death at 18 days	yes	congenital	floppy infant, tachydyspnoea, lactic acidosis plasma, and CSF	this study
60453	male	c.3G>C c.517C>T	p.Met1Ile p.Gln173∗	normal	ND	ND	3 months	alive for 36 years	yes	3 months	motor developmental delay, muscular hypotonia, exercise intolerance, normal mental development, and lactic acidosis	Lalive d'Epinay et al. (“fall 1”)3
60455 b	male	c.412C>T c.1137_1143del	p.Arg138∗ p.Gly380Leufs∗16	normal	ND	ND	1 week	death at 11 months	yes	congenital	muscular hypotonia, moderate motor retardation, and lactic acidosis depending on exercise	this study
62014 b	female	NA	NA	ND	ND	ND	1 week	death at 7 months	ND	congenital	muscular hypotonia and motor retardation	this study
60456 c	male	c.3G>C c.672C>A	p.Met1Ile p.Tyr224∗	normal	ND	ND	3 months	alive for 35 years	yes	3 months	motor developmental delay, exercise intolerance, normal mental development, and lactic acidosis depending on exercise	Lalive d'Epinay et al. (“fall 3”)3
62013 c	female	NA	NA	normal	ND	ND	10 weeks	death at 19 years	yes	10 weeks	motor developmental delay, exercise intolerance, normal mental development, esotropia, and nystagmus	Lalive d'Epinay et al. (“fall 2”)3
60182 d	male	c.1131+5G>A c.1131+5G>A	splicing defect	I, II+III, IV, and PDHc	impaired	impaired	1 year	death at 12 years	yes	18 months	muscular hypotonia, muscle weakness, and exercise intolerance	Morava et al. (case 1)6
60183 d	female	c.1131+5G>A c.1131+5G>A	splicing defect	I, II+III, IV, and PDHc	impaired	impaired	birth	alive for 10 years	yes	5 months	lactic acidosis and exercise intolerance	Morava et al. (case 2)6
60186	female	c.1131+5G>A c.1131+5G>A	splicing defect	normal	impaired	impaired	3.5 years	alive for 41 years	yes	congenital	lactic acidosis and cerebrovascular accident	van Ekeren et al. (case 12)4
62216	female	c.672C>A c.870del	p.Tyr224∗ p.Gln291Argfs∗8	I, II, III, IV, and very high CS	impaired	ND	birth	death at 10 months	yes	4 months	lactic acidosis	this study
62217	male	c.101+?_222-?del c.101+?_222-?del	ND ND	I, II, III, IV, and very high CS	impaired	ND	4 months	death at 8 months	yes	congenital	lactic acidosis, seizures, paresis of upper-left limb, dilation of brain ventricles, and axial hypotonia	this study
62218	female	c.221+1G>A c.1213C>T	splicing defect p.Gln405∗	I, II, III, IV, and very high CS	ND	ND	10 months	alive for 12 years	yes	congenital	lactic acidosis and severe muscle weakness	Di Rosa et al., (case 3);7 this study

Abbreviations are as follows: OXPHOS, oxidative phosphorylation; AO, age of onset; CM, cardiomyopathy; CSF, cerebrospinal fluid; NA, no material available; ND, not determined; I, complex I; II+III, succinate cytochrome c oxidoreductase; IV, cytochrome c oxidase; V, oligomycin-sensitive ATPase; PDHc, pyruvate dehydrogenase complex; and CS, citrate synthase.

^aInvestigated by exome sequencing.

^bIndividuals 60455 and 62014 are siblings.

^cIndividuals 60456 and 62013 are siblings.

^dIndividuals 60182 and 60183 are siblings.