The long road to a rare diagnosis: A Malaysian case of childhood-onset progressive myoclonus, ataxia, and retinal dystrophy with biopsy features suggestive of mitochondrial dysfunction.

ObjectiveMyoclonus is a hyperkinetic movement disorder characterized by sudden, involuntary jerks due to muscle contraction or brief lapses of muscular activity and may arise from diverse conditions. When accompanied by cerebellar dysfunction and retinal involvement, it suggests a heterogeneous spectrum of disorders, including mitochondrial, repeat-expansion, and other inherited neurogenetic disorders. In Malaysia, the diagnosis of rare diseases remains challenging because of phenotypic overlap and resource limitations. We illustrate the diagnostic dilemma of a possible mitochondrial disorder when definitive testing is not readily accessible.MethodsWe describe a woman in her early 40s with childhood-onset myoclonic jerks, progressive gait instability, cerebellar signs, and cognitive decline.ResultsOphthalmic assessment showed reduced visual acuity, optic disc pallor, and electroretinographic findings consistent with cone-rod dystrophy. Audiometry demonstrated bilateral sensorineural hearing loss. Brain computed tomography showed cerebral and cerebellar atrophy. Muscle biopsy revealed preserved architecture without ragged-red fibers, but oxidative enzyme histochemistry showed subsarcolemmal mitochondrial aggregates suggestive of mitochondrial dysfunction. Whole-exome sequencing did not identify a causative variant. Given the combination of cerebellar features and retinal dystrophy, a repeat-expansion disorder, particularly spinocerebellar ataxia type 7, remained a key differential diagnosis. Targeted repeat-expansion testing and mitochondrial deoxyribonucleic acid analysis were not performed because of patient-centered considerations. Despite disease progression, multidisciplinary follow-up was maintained, including structured physiotherapy and annual ophthalmologic surveillance.ConclusionThis case highlights the importance of pragmatic care planning in resource-limited settings and maintaining comprehensive care for patients without a definitive molecular diagnosis. It also emphasizes the need to strengthen rare disease diagnostic pathways to support shared decision making.