From confusion to diagnosis: a rare case of melas syndrome in a patient with familial consanguinity, recurrent stroke-like episodes, and concurrent FSGS

MELAS syndrome (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) is a rare mitochondrial disease characterized by a collection of symptoms including stroke-like episodes, seizures, visual disturbances, motor weakness, and headache with an estimated prevalence of 0.18 per 100,000 individuals. Approximately 80% of instances are linked to the m.3243 A > G mutation in the MT-TL1 gene. A 45-year-old female with a history of diabetes mellitus, focal segmental glomerulosclerosis, and hypertension presented to the Emergency Department with a 6-day history of acute-onset confusion, headache, progressive vision loss, and right-sided hemiparesis, accompanied by language impairment reported by family members and a relevant past medical history. On examination, the patient was disoriented, with impaired comprehension and an inability to follow commands. Family history was significant to focal segmental glomerulosclerosis (FSGS), diabetes, hypertension, and cerebrovascular accidents (CVA). Brain MRI revealed widespread and diffuse tissue changes with restrictive heterogeneous features, predominantly involving the left temporal lobe. A significant lactate peak was demonstrated in Magnetic Resonance Spectroscopy (MRS). The diagnosis of MELAS syndrome was presumed after imaging findings and confirmed with genetic testing, where it revealed the presence of a mutation in the m.3243 A > G mitochondrial gene. The patient initiated treatment with intravenous L-arginine along with oral taurine as prophylaxis. Despite titrating her treatment to the maximum dosage, she experienced minimal improvement and subsequently developed generalized seizures and altered mental status. This case highlights the diagnostic and therapeutic challenges of late-onset MELAS syndrome, emphasizing its multisystemic nature and phenotypic variability. Despite standard treatments, partial clinical improvement underscores the need for novel, targeted therapies and multidisciplinary care to address the limitations of current management approaches.