Table 2.

Summary of 14 patients diagnosed with a defect in EFG1: GFM1 mutations, respiratory chain enzyme analysis and clinical presentation.

ID	GFM1 mutations (NM_024996.5)	RC activity of the five complexes						Clinical presentation	References
Tissue	I	II	III	IV	V
P1	Homozygous: c.521A>G p.N174S	Muscle Fib.	52% 40%		69%	54% 18%		Female, first cousin parents, cesarean section, IUGR, microcephaly, stiffness, few movements. From day 10, severe metabolic acidosis. From day 7, progressive liver dysfunction. Died 27 days old. Postmortem liver examination: cholestasis and necrosis. Brain: hypoplasia of corpus callosum, cystic lesion in the basal ganglia	Coenen et al.
P2	Homozygous: c.521A>G p.N174S	Fib.	13%			31%		Male sibling of P1. Blood lactate up to 9.3 mmol/l. Brain US: generalized atrophy, small corpus callosum. Delayed growth and development, increased muscle tone in upper extremities. Signs of liver failure from week 7. Died five months old.
P3	Compound heterozygous: c.961T>Ca/ c.1765-2_1765-1delb p.S321P/p.G589	Muscle Fib.	38%c	51%c	50%c	10%c 20%c		Unrelated parents. IUGR. Metabolic acidosis, blood lactate 22 mmol/l, hyperbilirubinemia, hypoalbuminemia soon after birth. Mild facial dysmorphism. Large patent ductus arteriosus. Brain MRI normal, MRS showed elevated lactate. Developed ascites, coagulopathy, respiratory failure. Died 9 days old. Autopsy: liver steatosis, microvesicular cholestasis, pesudoacinar formation, bile duct proliferation, iron deposition. Kidney lipid accumulation. Neuropathology: porencephaly, microcephaly, dysgenesis of cingulated gyri.	Antonicka et al.
P4	Compound heterozygous: c.961T>Ca/ c.1765-2_1765-1delb p.S321P/p.G589	Fib.				26%c		Female sibling of P3. IUGR, oligohydramnios. Induced delivery week 24, died 45 min later. Liver: excess iron.
P5	Compound-heterozygous: c.139C>T/c.1487T>Gd p.47X/M496R	Muscle Fib.	~ 59% ~ 40%	~ 109% ~ 106%	Np ~ 48%	~ 53% ~ 20%	Np ~ 47%	Female, unrelated parents. Respiratory stress, metabolic acidosis 2 days old. Episodes with hyper- and opisthotonus. Serum lactate 10.2 mmol/l. Elevated transaminases. From age six months, episodic metabolic acidosis, with lactate up to 86 mM. Psychomotor regression, microcephaly, hypotonia, limb spasticity, nystagmus. Enlarged liver. Brain MRI: polymicrogyria, diffuse signal abnormalities in the cerebral, cerebellar and pontine WM, multiple cystic lesions. Died 14 months old.	Valente et al.
P6	Homozygous: c.748C>T p.R250W	Muscle Fib.	~ 113% ~ 34%	~ 145% ~ 115%	~ 98% ~ 79%	~ 136% ~ 25%		Female, SGA, second cousin parents. Onset two days old with feeding problems and reduced consciousness. Psychomotor retardation, hypotonia, poor eye contact. Onset of seizures 8 weeks old. Borderline microcephaly, wandering eye movements. Hypertonia of extremities, brisk reflexes. Blood lactate 4.9, CSF lactate 2.5. Brain MRI: small frontal cortex, thin corpus callosum, delayed myelination. Hepatomegaly from age 8 months. Died 2 years old due to pneumonia.	Smits et al.
P7	Compound heterozygous: c.539delG/c.688G>A p.G180Afs*11/p.G230S	Fib.	68%			47%		Female, non-consanguineous parents. IUGR. Microcephaly. Onset two days old with lactic acidosis, lactate up to 25 mmol/l, CSF lactate 12 mmol/l. Abnormal liver biochemistry. Recurrent episodes of lactic acidosis. Hypotonia, myopathic facies, slight facial dysmorphism. Progressive liver dysfunction with hepatomegaly. FTT, psychomotor retardation. Nystagmus, ptosis. Tube feeding. Died 8 months old. Brain MI: global cystic changes in subcortical WM, lesions in putamen and globus pallidus, enlarged ventricles.	Balasubramaniam et al.
P8	Homozygous: c.2011C>T p.R671C	Muscle Fib.	~ 84% ~ 62%	~ 86% ~ 428%	~ 80% ~ 401%	~ 30% ~ 183%	~ 113% ~ 154%	Male, consanguineous parents. Feeding difficulties and vomiting immediately after birth. Microcephaly, coarse facies, hypotonia, dystonia, polyneuropathy, psychomotor retardation. Tube feeding. No seizures, but abnormal eeg. Died 4 years old. Brain MRI: vermis hypoplasia, pontine atrophy. Supratentorial atrophy, parenchymal loss of WM, cortex, basal ganglia.	Galmiche et al.
P9	Homozygous: c.1193T>C p.L398P	Muscle Fib.	~ 93%	~ 74% ~ 200%		~ 33% ~ 38%		Male, consanguineous parents. Low birth weight. Spasticity with hyperreflexia and contractures. Developed hypoglycemia, metabolic acidosis, elevated lactate 30 h old. Abnormal liver biochemistry. Recurrent episodes of lactic acidosis. Developmental delay, microcephaly, dysmorphism, hypospadias. Died 20 months old.
P10	Compound heterozygous: c.720delT/c.2011C>T p.E241NfsX1/ p.R671C	Muscle Fib.				↓↓ ↓		Onset before 1 week of age. Hypsarrhythmia, failure to thrive, dystonia, squint.	Calvo et al.
P11	Compound heterozygous: c.720delT/ c.910A>G p.E241NfsX1/p.K304E	Liver	↓↓			↓↓		Onset before one year of age. Developmental delay, seizures, hypotonia, episodic metabolic acidosis.
P12	Homozygous: c.130_137delins p.E44_I46delinsKKK	Muscle Fib.	~ 89% ~ 155%	~ 137% ~ 329%	~ 241% ~ 260%	~ 65% ~ 116%		Male, parents related. Small birth parameters. Dysmorphic facial features. Onset on day 1 with lactic acidosis and hypoglycemia. Lactate up to 23 mmol/l. Brain CT: cortical atrophy, hypodense areas in WM. Psychomotor retardation and liver failure. Died four months old. Brain autopsy showed polymicrogyria. Liver histology: cirrhosis.	This paper
P13	Homozygous: c.130_137delins p.E44_I46delinsKKK	Muscle Fib.	~ 137% ~ 236%	~ 159% ~ 200%	~ 314% ~ 236%	~ 98% ~ 77%		Younger sister of patient 12. Small for GA. Onset day 1 with hypoglycemia and lactic acidosis. Liver failure and FTT. Died 14 days old.
P14	Compound heterozygous: c.964G>A/ c.1655T>G p.E322K/p.V552G	Liver Muscle Fib.	~ 9% ~ 102% Np	~ 154% ~ 187% ~ 152%	~ 53% ~ 229% ~ 126%	~ 7% ~ 95% ~ 54%		Female, non-consanguineous parents. Microcephaly from birth. Neonatal onset with lactic acidosis, serum lactate 25 mmol/l. Liver dysfunction in the first week. Epilepsy and hypertonia form 2 months. Brain MRI: severe leukodystrophy. Died 3 months old.

Residual activities expressed as a percent of the lowest control value stated. Arrow indicate significance at decreased levels RC activity.

Fib. = fibroblasts.

^aPreviously reported as c.1068T>C.

^bPreviously reported as c.1872_delAG.

^cResidual activities expressed as a percent of control mean value.

^dPreviously reported as c.1478T>G.