Perineal dysmorphism and patellar luxation in SLC35A2-CDG: a new piece in the glycosylation puzzle
Year: 2026
Type: article
Study design: Case Report
Abstract: Background. Congenital disorders of glycosylation (CDG) represent a group of inherited metabolic diseases characterized by multisystem involvement. SLC35A2-CDG (OMIM #300896) is a rare X-linked subtype resulting from pathogenic variants in the SLC35A2 gene, which encodes the UDP-galactose transporter. Approximately 70 cases have been documented, predominantly presenting with early-onset epilepsy, developmental delay, hypotonia, and dysmorphic features. Phenotypic variability remains incompletely characterized, and novel features continue to expand the clinical spectrum. Case Presentation. We report a 6-year-old girl with SLC35A2-CDG harboring a novel de novo heterozygous frameshift variant (NM_005660.3: c.105_106insCG, p.K36Rfs*6). The patient presented with epileptic spasms, severe global developmental delay, hypotonia, and distinctive dysmorphic features including strabismus and inverted nipples. Notably, she exhibited bilateral patellar luxation and perineal dysmorphism with a shortened anogenital distance, features that have not been previously associated with SLC35A2-CDG. Additional findings included a thin corpus callosum, a pineal cyst, right-sided aortic arch, bilateral vesicoureteral reflux, and central hypothyroidism. Oral D-galactose supplementation was initiated and resulted in subjective improvements in language comprehension, pain responsiveness, and motor function, although no improvement in seizures was observed. Conclusions. This casa may expand the phenotypic spectrum of SLC35A2-CDG by describing bilateral patellar luxation and perineal dysmorphism as potentially novel clinical features, along with a previously unreported pathogenic variant. Recognition of such unique features is crucial for improving our clinical understanding of this rare disorder, guiding differential diagnosis, and contributing to a more refined characterization of genotype–phenotype correlations.
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7223475225