Open AccessExpansion of the clinical and neuroimaging spectrum associated with NDUFS8 ‐related disorder
Author(s) -
Andzelm Milena M.,
Balasubramaniam Shanti,
Yang Edward,
Compton Alison G.,
Millington Kate,
Zhu Jia,
Anselm Irina,
Rodan Lance H.,
Thorburn David R.,
Christodoulou John,
Srivastava Siddharth
Publication year - 2022
Publication title -
jimd reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.412
H-Index - 25
ISSN - 2192-8312
DOI - 10.1002/jmd2.12303
Subject(s) - neuroimaging , white matter , medicine , leukodystrophy , pathology , neuroscience , brainstem , basal ganglia , magnetic resonance imaging , psychology , disease , central nervous system , radiology
Abstract Biallelic pathogenic variants in NDUFS8 , a nuclear gene encoding a subunit of mitochondrial complex I, result in a mitochondrial disorder characterized by varying clinical presentations and severity. Here, we expand the neuroimaging and clinical spectrum of NDUFS8‐related disorder. We present three cases from two unrelated families (a girl and two brothers) homozygous for a recurrent pathogenic NDUFS8 variant [c.460G>A, p.(Gly154Ser)], located in the [4Fe‐4S] domain of the protein. One of the patients developed auto‐antibody positive diabetic ketoacidosis. Brain MRIs performed in two of the three patients demonstrated diffuse cerebral and cerebellar white matter involvement including corticospinal tracts, but notably had sparing of deep gray matter structures. Our report expands the neuroimaging phenotype of NDUFS8‐related disorder to include progressive leukodystrophy with increasing brainstem and cerebellar involvement, with relative sparing of the basal ganglia. In addition, we describe autoimmune diabetes in association with NDUFS8‐related disorder, though the exact mechanism of this association is unclear. This paper provides a comprehensive review of case presentation and progressive neuroimaging findings of three patients from two unrelated families that have an identical pathogenic NDUFS8 variant, which expands the clinical spectrum of NDUFS8‐associated neurological disease.