Objective:

To describe two new cases of LYRM7-associated mitochondrial complex III deficiency and review the disorder’s clinical spectrum.

Approach:

• Case series: The report describes two brothers from a consanguineous family who carried the same pathogenic LYRM7 variant but had different disease courses.
• Genetic testing: Whole-exome sequencing identified the variant, which was confirmed by Sanger testing.
• Literature review: The authors reviewed published cases to place the brothers’ presentations in the context of the known phenotype.

Key Findings:

• One brother had relapsing ataxic episodes, longitudinally extensive transverse myelitis, and optic neuritis that initially suggested inflammatory demyelination, including NMOSD.
• The younger brother had a more rapidly progressive course and died early.
• Imaging showed cystic white matter changes suggestive of mitochondrial leukodystrophy and longitudinally extensive transverse myelitis in both patients.
• The cases demonstrate marked variability between siblings with the same pathogenic variant and add atypical demyelinating-like presentations to the reported spectrum.

Interpretation:

The authors report that LYRM7-associated mitochondrial disease can resemble inflammatory demyelinating disease, complicating diagnosis. They emphasize early genetic evaluation in children with recurrent demyelinating-like episodes, atypical progression, or familial neurologic disease.

Limitations:

• The new clinical observations are based on two related patients.
• The provided article context does not report the literature review’s scope or methods.

Sources:

• Khan GS, Bayat S, Azizimalamiri R, et al. J Mol Neurosci. 2026;76:72. doi:10.1007/s12031-026-02527-8.