A case with mutation of Vps13D: Leigh syndrome or spinocerebellar ataxia?

Introduction: Leigh syndrome (LS), the most common childhood mitochondrial disorder, has characteristic clinical and neuroradiologic features. The patients present with identical, symmetrical lesions in the basal ganglia or brainstem on MRI , despite leigh syndrome has high genetic, clinical heterogeneity and age of onset varies from patients. Case: A six-month-old male patient, born to a nonconsanguineous family, was presented with epileptic spasms. Neurological examination showed developmental delay, lack of eye contact and truncal hypotonia, feeding difficulties with loss of appatite. Head control was not acquired yet, distonia was seen. The electroencephalogram was showed hypsarrhythmia and antiepileptic treatment was started. Brain MRI showed symmetric lesions of corpus striatum with hyperintensity T2-weighted images and restricted diffusion. Whole exome sequencing (WES) test and mitochondrial DNA testing was normal for LS. CGH array was also performed and found normal. Mitochondrial cocktail was started. Although genetic tests resulted normal; clinical, MRI findings and improvement of symptoms with cocktail directed us to reanalyze WES for LS. Homozygous Vps13D mutation with heterozygous parents is detected which causes spinocerebellar ataxia, newly identified gene for LS. Conclusion: The genetic causes of LS are heterogeneous with a poor genotype-phenotype correlation. Both nuclear and mitochondrial DNA mutations in over 60 genes have been shown so far. In most patients, these genetic tests have accelerated the discovery of new genes involved in LS, providing new insights into the pathophysiological mechanisms. This report highlights typical clinical presentation and MR findings with newly reported genetic mutation.
Keywords: Vps13D, Leigh syndrome, whole exome sequencing