Table 4.
Reported cases with MMDS type 4.
| Ref. | Nb of Patients (Nb and Origin of Families) | Age at Onset/Age at Death | Metabolic Findings | Impaired Mitochondrial Proteins | Ophthalmological Findings | Clinical Feature | Brain MRI/Spectroscopy | Genotype (ISCA2: NM_194279) |
|---|---|---|---|---|---|---|---|---|
| [86] | 6 (5F, Saudi Arabia) | 3–7 m/11 m to 5 y (n = 4), alive (13–16 m, n = 2) | Negative | Complex I | Optic atrophy (6/6) | Spasticity, severe PMR | Lesions in cerebral (PV region to U fibers) and cerebellar WM, CC, internal capsule | c.[229G > A]; [229G > A], p.[(Gly77Ser)]; [(Gly77Ser)] |
| [87] | 1 (Saudi Arabia) | NA | NA | NA | NA | Neurodegeneration | Lesions in WM/Lactate peak | c.[229G > A]; [229G > A], p.[(Gly77Ser)]; [(Gly77Ser)] |
| [50] | 2 (2F, unknown) | 2 d, NA/12 d (n = 1), alive at 12 y | Elevated lactate (bl, CSF 1/2) | Complexes I, II, lipoylated protein | No | FD, spasticity (1/2), severe hypotonia | Leukodystrophy (1/2) WM atrophy (1/2) | c.[154C > T]; [154C > T], p.[(Leu52Phe)]; [(Leu52Phe)] c.[313A > G]; [313A > G], p.[(Arg105Gly)]; [(Arg105Gly)] |
| [88] | 10 (9F, Saudi Arabia) | 3–7 m/11–28 m (n = 5), alive between 10 to 34 m (n = 5) | Elevated lactate and glycine levels (bl, 2/2) | NA | Optic atrophy and nystagmus | Seizures 2/10, axial hypotonia with peripheral spasticity | Severe PMR/lactate peak (1/2), glycine peak (2/2) | c.[229G > A]; [229G > A], p.[(Gly77Ser)]; [(Gly77Ser)] |
| [89] | 2 (2F, Saudi Arabia) | 3–6 m/2 y, alive at 3 y | Elevated lactate (CSF), glycine, and glutamate (CSF, ur) levels | Complexes II, IV, lipoylated proteins, mtDNA depletion | Optic atrophy and nystagmus | PMR (2/2), spasticity, macrocephaly and syndactyly (1/2) | Lesions in cerebral (PV region to U fibers 1/2) and cerebellar WM (2/2), CC, internal capsule, spinal cord (1/2)/lactate peak (2/2) | c.[229G > A]; [229G > A], p.[(Gly77Ser)]; [(Gly77Ser)] |
| [91] | 1 (Italy) | 2 m/3 m | Initially normal, elevated lactate level (CSF, later) | Complexes II and IV (muscle) | Nystagmus, normal fundus oculi | Progressive severe hypotonia | Lesions in cerebral grey and WM (U fibers, CC, spinal cord) | c.[295delT]; [334A > G], p.[(Phe99Leufs*18)]; [(Ser112Gly)] |
| [92] | 1 (Iran) | 7 m/NA | NA | NA | NA | Hypotonia, irritability, malaise, muscle stiffness | Lesions in PV WM; centrum semiovale, cerebellar peduncles/peak of lactate, increase choline | c.[355G > A]; [355G > A], p.[(Ala119Thr)]; [(Ala119Thr)] |
| [93] | 1 (Yemen/Tunisia) | 11 m/alive 11 y | Mildly elevated lactate (bl, CSF) | All respiratory chain complexes | Nystagmus | Severe hypotonia, PMR, spasticity later, | Progressive lesions in PV region, genu, splenium (edema), thick CC, no spinal cord involvement/lactate peak | c.[5C > A]; [413C > G], p.[(Ala2Asp)]; [(Pro138Arg)] |
Bl: blood; CC: corpus callosum; CSF: cerebrospinal fluid; d: day(s); F: families; FD: feeding difficulties; m: month(s); MRI: Magnetic resonance imaging; NA: not available; PMR: psycho-motor regression; PV: periventricular; ur: urinary; WM: white matter; y: year(s).