ATP Synthase Deficiency due to TMEM70 Mutation Leads to Ultrastructural Mitochondrial Degeneration and Is Amenable to Treatment

Table 1

Clinical and epidemiological data.

	Child I,; 2000	Child II,; 2004	Child III,; 2005	Child IV,; 2006	Child V,; 2010	Child VI,; 2013
Pregnancy and birth details	Intrauterine reduced child movements, APGAR 7/3/5, cord pH 7.17	Anhydramnion, APGAR 5/7/7, cord pH 7.21	n.a.	Anhydramnion, APGAR 7/8/7, cord pH 7.16	n.a.	Reduced child movements, anhydramnion since the 29th week of gestation, APGAR 6/6/n.a., cord pH 7.29
Morphological stigmata	Dysmorphic ears	Dysmorphic ears	n.a.	Dysmorphic ears	n.a.	Dysmorphic child
Organ impairment	Noncompaction cardiomyopathy (NCCM), hepatomegaly	Noncompaction cardiomyopathy (NCCM), hepatomegaly	n.a.	Noncompaction cardiomyopathy (NCCM), hepatomegaly	n.a.	Noncompaction cardiomyopathy (NCCM), hepatomegaly,
Clinical course	Failure to thrive, mild retardation, rarely metabolic crises	Death 55 hours postpartum	No hospitalisation	Failure to thrive, retardation, isolated metabolic crises	n.a.	Death 58 hours postpartum
Long-term course	Mental retardation, reduced growth, clinical contact during respiratory infections, isolated metabolic crises; child was followed up to the age of 13 years		Reported to be healthy	Mental retardation, reduced growth, clinical contact during respiratory infections, isolated metabolic crises, periodic nutrition via endogastric tube; child was followed up until age of 7 years	Reported to be healthy
Routine laboratory	Lactate 15 mmol/L, 3-MGA elevation	Lactate 32 mmol/L, 3-MGA elevation	n.a.	Lactate 17 mmol/L, 3-MGA elevation	n.a.	Lactate 39 mmol/L, 3-MGA not tested
Muscle; light microscopy	No path. findings, no COX-negative fibres, no ragged-red fibres	No path. findings, no COX-negative fibres, no ragged-red fibres	n.a.	No path. findings, no COX-negative fibres, no ragged-red fibres	n.a.	No muscle biopsy performed
Muscle; biochemistry	Reduced activity in complexes I, II, III, and IV, complex V-activity 69 nmol/min/mg	Almost complete deficiency on native-PAGE	n.a.	Reduced activity in complex I, almost complete deficiency on native-PAGE	n.a.	n.a.
Genetic findings	No changes in SCO2 (cytochrome c oxidase assembly gene)	n.a.	n.a.	No mtDNA deletions or m.8993 mutation in MT-ATP6 gene; (8993 restriction fragment length polymorphism)	n.a.	n.a.
Status of TMEM70 c.317-2A-G	Homozygous	n.a.	n.a.	Homozygous	Heterozygous	Homozygous

Year of birth; for example, 2000 means the child was born in 2000.