Table 1.
Summary of clinical findings in individuals with NDUFS3-related LS.
| Patient and source of study | Proband A, this study | MITO036–33463; [19] | Patient 1; [15] | Patient 2 (Fetus); [15] | Patient; [16] |
|---|---|---|---|---|---|
| Gender | Male | NR | Male | NR | Male |
| Age of onset | 5 years | NR | 9 years | NR | 7 months |
| Symptoms at onset | Ataxia and motor deterioration | Developmental delay, muscular hypotonia, lactic acidosis, rapid disease progression | Neck stiffness | NR | Torticollis |
| Developmental abnormality | +, learning difficulties | Developmental delay | Normal until 9 years; neuromotor regression thereafter | NR | NR |
| Neurological and cerebellar findings | Ataxia, spasmodic torticollis, head tremor, nystagmus, mild bradykinesia, dystonia | Muscular hypotonia, rapid disease progression | Neck stiffness, progressive axial dystonia with oral and pharyngeal motor dysfunction, dysphagia, and a tetraparetic syndrome | NR | Torticollis |
| Brain MRI | Abnormal bilateral T2 hyperintensities in the medulla and minor vermian atrophy (age five). Small cavitary lesions in the tails of the right caudate nucleus; two punctate foci of cavitation and gliosis in the tail of the left caudate nucleus (Age 19). | NR | Focal, symmetrical, necrotic lesions in the thalamus, brain stem and white matter along with optic atrophy. | NR | High T2 signal intensity in the white matter of hemispheres, basal ganglia, and brain stem. |
| State of life at last consultation, age | Alive, 22 years old | NR | Died of rapid multisystem deterioration at 13.5 years of age | NR | Died at 2 years of age |
| Complex I deficiency - muscle | – | Reduced, 28% | Reduced, 50 (normal, 243 ± 60) | Reduced in amniocytes, value NR | Reduced in lymphoblastoids, value NR |
| Complex I deficiency - fibroblasts | Reduced, 66% | Reduced, 36% | Reduced, 16 (normal, 21 to 39) | NR | NR |
| Pyruvate (plus malate) oxidation (Complex I) - muscle | Normal | NR | Reduced, 20 (normal, 94 ± 48) | Reduced in amniocytes, 6.9 (normal, 7.7 to 9.5) | NR |
| Pyruvate (plus malate) oxidation (Complex I) - fibroblast | Normal | NR | Reduced, 2.7 (normal, 3.3 to 6.8) | NR | |
| Serum lactate; normal range is 0.580–2.10 mmol/L | Elevated; 4.10 mmol/L | Elevated, value not reported | NR, CSF, 2.7a | NR | Elevated, value not reported |
| Serum pyruvate; normal range is 55–145 umol/L. | Normal | NR | NR | NR | Elevated, value not reported |
| Consanguinity | No | NR | No | No | No |
| Paternal NDUFS3b variant | c.419G > A (p.Arg140Gln) | c.532C > T (p.Arg199Trp) | c.595C > T (p.Arg199Trp) | c.595C > T (p.Arg199Trp) | c.418C > T (p.Arg140Trp) |
| Maternal NDUFS3 b variant | c.381 + 6 T > C? (produces abberant isoforms) | c.532C > T (p.Arg199Trp) | c.434C > T (p.Thr145Ile) | c.434C > T (p.Thr145Ile) | c.595C > T (p.Arg199Trp) |
“+” denotes the presence of a feature; “− “denotes the absence of a feature; “NR” represents not reported.
b
, CSF Lactate 2.7 mmol/L (normal < 2.0).
b
, Variant nomenclature in NDUFS3 based on NM_004551.2. “?” – denotes that the variant may be de novo, but also may be maternally inherited.