Table 2.
Reported patients with MMDS type 2.
| Ref. | Nb of Patients (Nb and Origin of Families) | Age at Onset/Age at Death | Metabolic Findings | Impaired Mitochondrial Proteins | Cardiomyo- pathy | Clinical Feature | Brain MRI/Spectroscopy | Genotype (BOLA3:NM_212552.2) |
|---|---|---|---|---|---|---|---|---|
| [47] | 1 (East Indian) | 4 m/11 m | High glycine level (bl, ur) | Complexes I and II, PDH, lipoylated protein | Dilated | FD, lethargy, respiratory distress, HMG, DD | NA | c.[123dupA]; [123dupA], p.[(Glu42Argfs*13)]; [(Glu42Argfs*13)] |
| [65] | 2 (1F, unknown) | <1 m/3 m | High pyruvate (bl, ur), lactate (bl, ur), and glycine levels (bl) | Complexes I, II, IV, PDH, lipoylated protein | Hyper-trophic | FD, SE, hypotonia, progressive encephalopathy | Delayed myelination, supra-, PV, and bifrontal and biparietal hyperintense lesions (T2) | c.[200T > A]; [200T > A], p.[(Ile67Asn)]; [(Ile67Asn)] |
| [66] | 3 (3F: Australia, India, African- American) | 6–8 m/7 m, 22 m, 11 y | High lactate (bl), glycine (CSF) levels | Complex II (n = 1/3), PDH (n = 1/2), lipoylated protein (n = 2/2), GCS (n = 3/3) | Hyper-trophic (n = 2/2) | FD, SE (n = 1/3), Myoclonus (2/3), SP and severe PMDD (1/3), skills regression (2/3), optic atrophy (n = 2/3) | PV WM and spinal cord lesions (n = 1/3), subcortical fibers lesions (n = 1/3) LD (n = 2/3), cerebral and cerebellar atrophy (n = 1/3) | c.[136C > T]; [136C > T], p.[(Arg46*)]; [(Arg46*)] |
| [67,68] | 4 (4F, Japan) | <1, 2, 6 m/3–11 m | Metabolic acidosis | Combined complex deficiencies (n = 4/4) | Hyper-trophic (n = 3/4) | Renal, respiratory, and/or liver failures, SE, FCMD (n = 1) | NA | c.[287A > G]; [287A > G], p.[(His96Arg)]; [(His96Arg)] (3/4) c.[225_229del]; [287A > G], p.[(Lys75Asnfs*9)]; [(His96Arg)] |
| [50] | 2 (1F, India) | 5–7 m/8 m | High pyruvate (bl), lactate (bl, CSF), glycine (bl, CSF, ur) levels | Complexes I, II, IV, PDH, lipoylated protein | No | FD, tetraparesis, hypotonia, PMDD | Diffuse demyelination/lactate peak | c.[136C > T]; [136C > T], p.[(Arg46*)]; [(Arg46*)] |
| [69] | 2 (unknown) | 18 m/alive at 12 y (n = 1) | NA | NA | NA | SPT (n = 1/2), skills regression, gait difficulty | PV and deep WM or fronto-parietal lesions/lactate peak (n = 1/1) | c.[295C > T]; [295C > T], p.[(Arg99Trp)]; [(Arg99Trp)] |
| [70] | 1 (unknown) | 8 m/15 m | High lactate (bl), tiglylglycine (ur) levels | PDH, lipoylated protein | NA | FD, hypertonicity then hypotonia, nystagmus | Symmetric ovoid areas and CC, cervical cord regions abnormal signal. PV, deep, subcortical WM lesions/lactate peak | c.[200T > A]; [220_222del], p.[(Ile67Asn)]; [(Glu74del)] |
| [71] | 1 (Japan) | 6 m/10 m | High lactate (bl, CSF), glycine (bl) levels | Complexes I, II, IV | Hypertrophic | FD, SE, eyelid movements, hypotonia, skill regression | Deep WM to spinal cord lesions | c.[287A > G]; [287A > G], p.[(His96Arg); [(His96Arg)] |
| [72] | 1 (England) | 18 m/alive at 8 y | Normal lactate (bl), high glycine (bl, ur) levels | PDH, normal RCC activity but low quantity of protein in complexes I and II | No | Ataxia, acute hemiparesis, cognitive regression, congenital hypothyroidism | subcortical WM, basal ganglia, brainstem and cerebellum abnormal signal and dysmyelination | c.[136C > T]; [176G > A], p.[(Arg46*)]; [(Cys59Tyr)] |
| [73] | 1 (South Africa) | 7 m/17 m | High lactate (bl), glycine (ur) levels | PDH | No | Sudden skill regression, floppiness, encephalopathy | Demyelination | c.[159dupT]; [159dupT], p.[(Asp54*)]; [(Asp54*)] |
Bl: blood; CC: corpus callosum; CSF: cerebrospinal fluid; DD: developmental delay; F: families; FCMD: Fukuyama congenital muscular dystrophy; FD: feeding difficulties; HMG: hepatomegaly; m: month(s); MRI: Magnetic resonance imaging; NA: not available; PDH: pyruvate dehydrogenase complex; PMDD: psycho-motor developmental delay; PV: periventricular; RCC: respiratory chain complexes; SE: seizures; SP: spasticity; SPT: spastic tetraparesis; Ur: urine; WM: white matter; y: year(s).