LAUSR

We read with interest the article by Miyauchi et al. about an 11yo male with Leigh-syndrome (LS) due a mutation in the NDUFA1 gene manifesting not only in the brain but also the spinal cord [1]. We have the following comments and concerns. Spinal cord affection is not infrequent in patients with mitochondrial disorders and particularly occurs in patients with LBSL, LS, KSS, LHON, MERRF, IOSCA, MIRAS, and PCH6 and rarely also in patients with CPEO, MELAS, and LHON [2]. Contrary to the statement in the discussion, spinal cord involvement in LS is more common than so far anticipated and has been repeatedly reported (Table 1) [3,4]. Spinal cord involvement in LS on MRI may manifest as focal or diffuse T2-hyperintensities or focal hyperintensities on DWI (Table 1). Autopsy may show grey/white matter necrosis or demyelination. According to Table 1, patients with NDUFA1 mutations manifest with phenotypic heterogeneity [1]. Is the reason for this variability the residual amount of complex-I activity, the location of the mutation within the gene, or genetic factors other than the NDUFA1 mutation? The patient had developed epilepsy at age 10 months [1]. Which kind of antiepileptic drug was given? Some of them (CBZ, VPA, PB, PHT) are mitochondrion-toxic and may worsen epilepsy and the phenotype [5]. Since NDUFA1 is X-linked, we should be informed if the mother and twin sister carried the mutation as well, and if they manifested clinically. In a number of Xlinked disorders, female carriers may manifest mildly or as males. Since the index case presented with T2-hyperintensities in the substantia nigra, it is conceivable that he manifested with features of Parkinson’s disease. Was this the case?