Table 1 Clinical, laboratory, and radiological features associated with VARS2 related mitochondrial disease
Variants | Other clinical signs | Neurological signs | Metabolic screening | Cardiological ultrasound | EEG | Head MRI | Reference |
|---|---|---|---|---|---|---|---|
Homozygous c. 1100C > T (p. Thr367lle) | No | Poor sucking, hypotonia, developmental delay, seizures, ataxia, nystagmus, microcephaly, limb spasticity | Lactic acidosis, | No | Epileptic abnormalities | Cerebellar atrophy, T2 hyperintensity of symmetrical periventricular white matter/corpus callosum | |
Heterozygous c.1100C > T (p.Thr367lle) plus c.1490G > A (p.Arg497His) | Cryptorchidism, chronic pancreatiti | Stridor, respiratory failure, hypotonia / hypertonia, developmental delay, limb spasticity, poor sucking, poor activity | Lactic acidosis | Hypertrophic cardiomyopathy | Epileptic abnormalities | Cerebral atrophy, hypoplasia of the vermis, T2 hyperintensity of thalamus and septum pellucidum | [2] |
Homozygous c. 1258G > A (p.Ala420Thr) | hepatosplenomegaly | Poor sucking, hypotonia, respiratory failure | Severe metabolic acidosis and lactic acidosis | Hypertrophic cardiomyopathy, biventricular dilation | NA | NA | [2] |
Heterozygous c.2557-2A > G plus c.1100C > T (p. Thr367lle) | Unusual facial features, congenital hip dislocation, | Hypotonia, hyporeflexia, microcephaly, stridor, irritability, staring episodes | lactic acidosis, urinary lactate, increased plasma alanine | Hypertrophic cardiomyopathy, moderate pericardial effusion, | NA | Cerebellar atrophy, moderate to severe diffuse cerebral | [2] |
Heterozygous c.1100C > T (p.Thr367lle) plus c.1150G > A (p.Asp384Asn) | No | Hypotonia, poor sucking, poor activity, developmental delay, seizures | lactic acidosis, increased plasma pyruvate | Hypertrophic cardiomyopathy | Epileptic abnormalities | Cerebellar atrophy, hypoplasia of corpus callosum | [2] |
Heterozygous c.1546G > T (p.Glu516*) plus c.2239G > A (p.Ala747Thr) | No | Poor sucking, hypertonia, stridor, developmental delay | lactic acidosis, urinary lactate | Hypertrophic cardiomyopathy and severe pulmonary hypertension | NA | NA | [2] |
Heterozygous c.1135G > A (p.Ala397Thr) plus c.1877C > A (p.Ala626Asp) | No | Hypotonia, myasthenia, developmental delay, dyspraxia, seizures | NA | Hypertrophic cardiomyopathy | NA | T2 hyperintensity of the peritrigonal white matter | [2] |
Heterozygous c.601C > T (p.Arg201Trp) plus c.1100C > T (p.Thr367Ile) | No | Hypertonia, apnea, microcephaly, exotropia, seizures | Lactic acidosis, urinary lactate and pyruvate, 2-Oxoisocaproic acid and 2-Oxo-3-methyl-N-valeric acid, plasma elevation of alanine | Hypertrophic cardiomyopathy, left ventricular function reducing | Epileptic abnormalities, resembling burst suppression patterns | Hypoplasia of the corpus callosum, the cerebellum accompanied by edema of the brain stem and the frontal white matter | [7] |
Heterozygous c.643C > T (p.His215Tyr) plusc.1354A > G (p. Met452Val) | PPHN | Poor sucking, hypertonia, poor activity, hyporeflexia | Severe metabolic acidosis and lactic acidosis | Hypertrophic cardiomyopathy | mild abnormal (showed no obvious sleep-wake cycles) | NA | This study |