SLC25A37 – Multiple Sclerosis

Two pediatric patients with relapsing‑remitting multiple sclerosis (RRMS) were found to harbor variants in iron homeostasis genes, including SLC25A37, via whole exome sequencing (PMID:30963028). SLC25A37 encodes a mitochondrial iron importer that is critical for heme synthesis and overall iron metabolism. In these patients, genetic findings suggested an iron‑responsive subtype of RRMS, where long‑term disease remission was correlated with regular iron supplementation. Although the identification of SLC25A37 variants in this setting raises a potentially important mechanistic link between iron deficiency and demyelination, the genetic evidence is based on only 2 unrelated probands. There is currently no extended family segregation data or functional assay directly testing SLC25A37’s role in multiple sclerosis pathology.

The overall genetic score remains limited because of the small number of affected individuals and the absence of replication or detailed functional data in the context of multiple sclerosis. In the multi‑patient re‐evaluation, similar observations support the notion that altered iron transport may contribute to disease modulation, yet additional studies are required to firmly establish causality and elucidate the underlying pathogenic mechanism. Key take‑home: While preliminary findings implicate SLC25A37 in an iron‑responsive variant of RRMS, cautious interpretation is warranted in clinical decision‑making until further evidence is available.

References

• Molecular genetics and metabolism reports • 2019 • Identification of an iron‑responsive subtype in two children diagnosed with relapsing‑remitting multiple sclerosis using whole exome sequencing PMID:30963028

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