Introduction: Iron-Sulfur Cluster (ISC) biogenesis is a vital cellular process in the mitochondria. It is required to produce various ISC-containing proteins which are present in the nucleus, mitochondria, and cytosol. ISC proteins are responsible for essential functions such as glycine cleavage and the formation of lipoic acid. ISCA2 encodes an A-type ISC protein involved in the assembly of mitochondrial iron-sulfur cluster (4Fe- 4S) which is important for electron transfer and mitochondrial function.
ISCA2 related Mitochondrial Disorder (IRMD) is a severe disorder of systemic energy metabolism, characterized by weakness, respiratory failure, lack of neurological development, lactic acidosis, hyperglycinemia and early death. ISCA2 gene is located on Chromosome 14q24.3 and has autosomal recessive inheritance.
Objective: In this report, we present the clinical and radiological features a subject homozygous for the common founder pathogenic variant; c.229G>A; p.Gly77Ser.
Conclusion: IRMD presents with infantile onset triad of progressive neurodevelopmental regression, nystagmus and optic atrophy. It is a rapidly progressive condition with death usually in first two years of life. It should be considered in infantile onset leukodystrophy.
Future studies are needed to understand the role of ISCA2 gene, the effect of its mutation, and any targets for future treatment strategies.
Key words: Neurodegenerative, Infantile leukodystrophy, Mitochondrial disorder, respiratory chain
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