Table 1 Clinical phenotypes of patients presenting CoQ10-dependent enzymatic deficiency associated with MRC defect
Patient | Tissue | Sex | Age at biopsy | Age of onset | Heredity | Familial history | Neurological symptoms | Muscular symptoms | Other symptoms | Muscle histology | Enzymology | Diagnosis or molecular analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients with molecular diagnosis | |||||||||||||
P01a | Fibroblasts | M | D1 | Neonatal | Recessive | Affected brother | Neonatal polyvisceral failure | Not done | Cx IV deficiency; segments II + III and G3P + III reduction | COQ2: homozygous mutation (c.437G > A; p.Ser146Asn) | |||
P02 | Muscle | M | 54y | 25y | Sporadic | No | Brain MRI: mild atrophy and lacunar strokes | CPEO | T2DM, hepatic steatosis, dyslipidemia | RRF (5–10 %) and Cox-fibers | Cxes I, II, IV and V deficiency; segments I + III and II + III reduction | Large-scale deletion of mtDNA | |
P03a | Fibroblasts | M | D1 | Neonatal | de novo | No | Hypotonia, epilepsy and diffuse brain lesions | Neonatal polyvisceral failure: respiratory distress, hepatic failure, hypertrophic CMP, lactic acidosis ++ | Not done | Cxes II and III deficiency; segments II + III and G3P + III reduction | MT-CYB: heteroplasmic mtDNA mutation (m.15635T > C; p.Ser297Pro) | ||
P04a | Fibroblasts | M | 15y | 11y | Recessive | No | Ataxic sensory axonal neuropathy | CPEO | RRF and Cox-fibers (40 %) | Cxes I, II, III and IV deficiency; segments II + III and G3P + III reduction | SANDO with multiple mtDNA deletions and homozygous mutation in POLG: (c.911T > G; p.Leu304Arg) | ||
P05 | Muscle | F | 54y | 45y | Recessive | No | Ataxic sensory axonal neuropathy | CPEO | Lipid accumulation, RRF and Cox-fibers (20 %) | Cxes I, II, III, IV and V deficiency; segments I + III and II + III reduction | SANDO with multiple mtDNA deletions and compound heterozygous mutations in POLG: (c.752C > T/c.2452G > A; p.Thr251Ile/p.Gly848Ser) | ||
P06a | Fibroblasts | M | D1 | Neonatal | Recessive | No | Encephalopathy and hypotonia | Severe lactic acidosis, methylmalonic aciduria | Not done | Cxes II, III and IV deficiency; segments II + III and G3P + III reduction | SUCLG1: compound heterozygous mutations c.97 + 3G > C/c.509C > G (p.Pro170Arg) | ||
P07 | Muscle | F | 18y | 4y | Recessive | Blindness in paternal family | Bilateral ptosis, proximal myopathy, dysphonia, dysphagia, exercice intolerance | Retinitis pigmentosa, cyclic vomiting, hyperCPKemia | Lipid accumulation | Cxes I and III deficiency; segments I + III and II + III reduction | MADD with mutations in ETFDH | ||
P08 | Muscle | F | 4 m | 4 m | Recessive | Affected sister | Encephalopathy with refractory migrating partial seizures | Lipid accumulation | Cx I, II, III and IV deficiency; segments I + III and II + III reduction | Malignant migrating partial seizures with compound heterozygous mutations in TBC1D24: (c.468C > A/c.686C > T; p.Cys156X/p.Phe229Ser) | |||
P09 | Fibroblasts | M | D1 | Neonatal | Recessive | No | Hypotonia | Hypertrophic CMP, dysmorphic, hepatic cytolysis, hypospadia | Glycogenic accumulation | Cxes II, III, IV and V deficiency; segments II + III and G3P + III reduction | CDG syndrome type Iq : homozygous mutation in SRD5A3 : (c.620T > G; p.Met207Arg) | ||
P10a | Fibroblasts | M | 3 m | Neonatal | de novo | No | Hypotonia, epilepsy, dysphagia | Dilated CMP, aortic dilatation | Glycogenic accumulation | Cxes III and IV deficiency; segments II + III and G3P + III reduction | 1p36 deletion syndrome | ||
Patients with no molecular diagnosis | |||||||||||||
P11 | Muscle | M | 76y | Adult | ? | No | Cerebellar ataxia | 2 RRF and Cox- fibers (20-30 %) | Cx IV deficiency; segments I + III and II + III reduction | Multiple mtDNA deletions | |||
P12a | Fibroblasts | F | 7 m | 6 m | ? | No | Leigh syndrome | Not done | Cx II deficiency; segments II + III and G3P + III reduction | mtDNA depletion, absence of mtDNA and POLG, SUCLA2, TK2 mutation | |||
P13a | Muscle | F | 41y | Childhood | Recessive | Consanguinity | Spastic tetraparesis, chorea, mental retardation | Myopathy | Glaucoma, cataract, lactic acidosis | RRF ++ | Cx I deficiency; segments I + III and II + III reduction | Absence of mtDNA and POLG, OPA1, OPA3 mutation | |
P14 | Muscle | F | 33y | 6 m | ? | No | Epilepsy, spastic diplegia, dystonia, dyskinesia, tremor | 1 Cox-fiber | Cxes III and V deficiency; segments I + III and II + III reduction | Absence of mtDNA and POLG, TTC19, DYT5 mutation | |||
P15 | Muscle | F | 28 y | Childhood | Recessive | Affected siblings | Encephalopathy, mental retardation | Normal | Cxes II, III and V deficiency; segments I + III and II + III reduction | Absence of mtDNA mutation | |||
P16 | Fibroblasts | M | 9y | Infancy | ? | No | Psychomotor retardation, behavior disorders, dystonia, dyspraxia and basal ganglia involvement at brain MRI (Leigh) | Normal | Cxes II and III deficiency; segments II + III and G3P + III reduction | Absence of mtDNA mutation | |||
P17 | Fibroblasts | F | D3 | D2 | ? | No | Unexplained severe respiratory failure | Normal | Cxes II, III deficiency; segments II + III and G3P + III reduction | Absence of mtDNA mutation | |||
P18 | Fibroblasts | M | 2y | D18 | ? | No | Encephalopathy with refractory epilepsy | Microcephaly | Normal | Cxes III and IV deficiency; segments II + III and G3P + III reduction | Absence of mtDNA mutation | ||