Edition of 06 May 2025

A new study published in Brain characterized biallelic variants in PTPMT1, which encodes a highly conserved mitochondrial tyrosine phosphatase that plays a crucial role in de novo cardiolipin biosynthesis. The variants were found among 6 individuals from 3 unrelated families with a complex, neonatal/infantile-onset neurological and neurodevelopmental syndrome associated with cardiolipin abnormalities. This phenotype comprises developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Various analyses confirmed the role of PTPMT1 in cardiolipin metabolism, whose homeostasis is essential for neurodevelopement. Futher pathophysiological information revealed that loss of PTPMT1 is responsible for mitochondrial structure anomalies and dysfunctions, and defined it as a new autosomal recessive primary mitochondrial disease.