Clinical Report: LYRM7-Associated Complex III Deficiency

Overview

A case series and literature review describes two brothers with pathogenic LYRM7 variants and markedly different clinical courses, broadening the reported phenotype of mitochondrial complex III deficiency. Their recurrent demyelinating-like presentations, including longitudinally extensive transverse myelitis and optic neuritis in one brother, illustrate how the disorder can resemble inflammatory neurologic disease.

Background

LYRM7-associated mitochondrial complex III deficiency is a rare mitochondrial disorder described as typically neurodegenerative. The report highlights diagnostic difficulty when neurologic manifestations resemble inflammatory demyelination, including neuromyelitis optica spectrum disorder. The brothers’ shared variant but differing courses also demonstrate intrafamilial clinical variability. The source identifies early genetic evaluation as relevant to diagnosis, counseling, and prognostication in children with recurrent demyelinating-like episodes, atypical progression, or familial neurologic disease.

Data Highlights

Key Findings

• The case series reports two brothers with the same pathogenic LYRM7 variant and markedly different clinical courses.
• One patient experienced relapsing ataxic episodes and inflammatory demyelinating-like features, including longitudinally extensive transverse myelitis and optic neuritis that mimicked neuromyelitis optica spectrum disorder.
• The younger sibling had a more rapidly progressive course with early mortality.
• Imaging in both patients showed cystic white matter changes suggestive of mitochondrial leukodystrophy and longitudinally extensive transverse myelitis; the report notes that these findings differ from classic acquired inflammatory demyelinating patterns.
• Whole-exome sequencing and confirmatory Sanger testing identified a pathogenic LYRM7 variant.
• The authors describe the cases and literature review as expanding the known phenotypic spectrum of LYRM7-associated complex III deficiency and identify mitochondrial disease masquerading as inflammatory demyelination as a diagnostic pitfall.

Conclusion

These two cases broaden the reported clinical spectrum of LYRM7-associated complex III deficiency and demonstrate substantial variability between affected siblings. Their presentations show that mitochondrial disease may resemble inflammatory demyelinating disease.

Related Resources & Content

1. Khan GS, Bayat S, Azizimalamiri R, et al., Journal of Molecular Neuroscience, 2026 — Expanding the Clinical Spectrum of LYRM7-Associated Mitochondrial Complex III Deficiency: Insights from New Cases and Literature Review
2. Parikh S, et al., Genetics in Medicine, 2017 — Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society
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