Imaging phenotype of multiple mitochondrial dysfunction syndrome 2, a rare BOLA3-associated leukodystrophy.

Abstract

Multiple mitochondrial dysfunction syndrome (MMDS) is a rare disorder of systemic energy metabolism associated with mutations in genes having a vital role in production of iron-sulfur clusters, important for the normal maturation of lipoate-containing 2-oxoacid dehydrogenases and for the assembly of the mitochondrial respiratory chain complexes. MMDS 2 associated with BOLA3 mutation presents in early infancy and is characterized by developmental regression, severe encephalopathy, optic atrophy, and cardiomyopathy. Neuroimaging phenotype associated with MMDS 2 has never been described in its entirety in literature, with few reported cases till date. None of the published cases mention findings demonstrated in our case, a proband with biallelic BOLA3 variants, such as necrotic/cavitary lesions within the centrum semiovale, restricted diffusivity within the white matter, areas of central enhancement within the centrum semiovale presumably related to leakage of contrast within the necrotic center, enhancement of bilateral optic nerves, and markedly elevated lactate on magnetic resonance spectroscopy.