Table 1 Demographic and clinical review of the eight homozygous c.1100C > T, p. Thr367Ile VARS2 encephalopathy cases. Data on P1-P6 are obtained from literature (see references); cases A and B are described in present study
From: VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype
Origin | Sex | First medical referral | Current age/death | Clinical and neurological signs | Lab tests | Brain MRI (spectroscopy) | OXPHOS study | |
|---|---|---|---|---|---|---|---|---|
P1a1 | Italy (Sardinia) | M | First months | Death at 8 years | Developmental delay, microcephaly, seizures, nystagmus, facial dysmorphia | n.a. | T2 hyperintensity in insulae, right fronto-temporal cortex, periventricular WM (lactate in frontal WM) | Complex I deficiency (25% residual activity) |
P22 | Poland | F | Birth | Alive at 5 years | Hypotonia, developmental delay, ataxia, seizures, pathological visual evoked potentials | n.a. | T2/FLAIR WM-hyperintensity, cerebral atrophy (lactate) | n.a. |
P3b2 | Afghanistan | F | 6 months | Death at 7 years | Microcephaly, severe hypotonia, developmental delay, nystagmus, seizures | Serum lactate 2.3 mmol/l (normal 0.55–2.00) | Cerebellar atrophy, T2 hyperintensity of dentate nuclei & thalami; thin corpus callosum | n.a. |
P4b2 | Afghanistan | F | 6 months | Death at 8 years | Progressive microcephaly, hypotonia, developmental delay, limb spasticity, seizures | Serum lactate 2.8 mmol/l (normal 0.55–2.00) | Cerebellar atrophy, T2 hyperintensity of dentate nuclei & thalami; thin corpus callosum | n.a. |
P5b2 | Afghanistan | M | Birth | Alive at 5 months | Hypotonia, progressive microcephaly | Serum lactate 4.4 mmol/l (normal 0.55–2.00) CSF lactate 3.08 mmol/l (normal 1.2–2.1) | Cerebellar hypoplasia | n.a. |
P63 | Portugal | F | Birth | Death at 28 months | Developmental delay, nystagmus, severe hypotonia, spastic tetraparesis, microcephaly, seizures, feeding difficulties | Serum lactate 2.72 mmol/L (normal 0.55–2.00) CSF lactate 1.45 mmol/L (normal 1.2–2.1) | Global atrophy, diffuse T2 WM-hyperintensity | Complex II + III: 2.6 nmol/min/mg (normal 2.6–12) |
A4 | Italy (Sardinia) | F | 11 months | 6 years old | Motor and language delay, hypotonia, limb spasticity; dysmorphisms. No seizures | Normal serum lactate | T2 hyperintensity in deep WM and posterior internal capsule; corpus callosum hypoplasia and cortical cerebellar atrophy (increased lactate and decreased NAA in cerebellar WM lesions) | Complex I and III deficiency |
B4 | Italy (Sardinia) | F | 2 years | 5 years old | Developmental delay, nystagmus, hypotonia, limb spasticity; facial dysmorphisms; seizures | Slightly increased serum lactate | First MRI: mega-cisterna magna with slight cerebellar atrophy; cerebellar atrophy and vermis hypoplasia at follow-up MRI (normal spectroscopy) | n.a. |