Introduction: Mitochondrial proteins carrying iron-sulfur (Fe-S) clusters are involved in essential cellular pathways such as oxidative phosphorylation, lipoic acid synthesis, and iron metabolism. NFU1, BOLA3, IBA57, ISCA2, and ISCA1 are involved in the last steps of the maturation of mitochondrial [4Fe-4S]-containing proteins and are responsible for Multiple Mitochondrial dysfunctions syndrome (MMDS) 1 to 5 respectively. Methodology: Rare case report with genetic confirmation and literature review. Results: 21 months old female born of consanguineous marriage with uneventful birth history presented with global developmental delay, failure to thrive, feeding difficulties and dystonia with no seizures. Microcephaly, plagiocephaly, nystagmus, truncal hypotonia, limb spasticity with brisk deep tendon reflexes and dystonic tremors noted. Neuroimaging showed diffuse vacuolating leukodystrophy with diffusion restriction extending to subcortical regions, dysmorphic appearance of lateral ventricles, cortical malformation, abnormal white matter changes in posterior limb of internal capsule and cerebellum, with restricted diffusion in lateral and dorsal cervical spinal cord. MR Spectroscopy showed a large lactate peak. Whole exome sequencing revealed a likely pathogenic homozygous variant in ISCA 1 gene at Exon 4 causative for MMDS5 confirmed with parental segregation analysis. Conclusion: This is the eighth reported case worldwide of MMDS 5 due to ISCA1 with a unique combination of neuroimaging findings of Indian cases and of those reported from abroad. In a child with CP where MRI shows the unusual combination of cortical malformation with cystic changes (suggestive of congenital/chronic etiology) along with restricted diffusion (which indicates an acute pathology), we must think of MMDS and consider genetic testing.

Ashwin Sardesai
Jawaharlal Nehru Medical College
India

Mahesh Kamate
Jawaharlal Nehru Medical College
India

Thanuja B.
Jawaharlal Nehru Medical College
India