GM3 synthase deficiency (GM3SD), also known as salt and pepper developmental regression syndrome, is a rare autosomal recessive congenital disorder of glycosylation caused by biallelic pathogenic variants in ST3GAL5. It is characterized by early onset epileptic encephalopathy, severe neurodevelopmental impairment, and sensory deficits. Routine metabolic screening tests are frequently non-specific, which may contribute to delayed diagnosis. We report a Turkish male infant who presented in early infancy with developmental delay and hypotonia, followed by early onset, refractory epilepsy and progressive neurodevelopmental regression. Feeding dysfunction progressed to complete loss of swallowing, necessitating gastrostomy and tracheostomy. Neuroimaging demonstrated diffuse cerebral atrophy and ventriculomegaly, and audiological evaluation revealed bilateral sensorineural hearing loss. Extensive metabolic investigations, including screening for congenital disorders of glycosylation, were non-diagnostic. Whole-exome sequencing identified a novel homozygous frameshift variant in ST3GAL5 (NM₀03896. 4: c. 726₇32del, p. (Met242Ilefs*35) ), classified as likely pathogenic, confirming the diagnosis of GM3SD. During follow-up, renal calculi and hepatobiliary abnormalities, including biliary sludge, gallstones, and transaminase elevation, were observed. This case highlights the severe neurological course and diagnostic challenges associated with ST3GAL5-related GM3SD and underscores the critical role of comprehensive genetic testing in infants with unexplained epileptic encephalopathy and developmental regression. Although renal and hepatobiliary abnormalities are not considered characteristic features of GM3SD, their occurrence during long-term follow-up emphasizes the need for careful multisystem surveillance in severely affected patients.
Gökalp et al. (Mon,) studied this question.