Acetazolamide treatment in late onset CDG type 1 due to biallelic pathogenic DHDDS variants.

Pathogenic variants in have been associated with either autosomal recessive retinitis pigmentosa or DHDDS-CDG. Heterozygous variants in have been described in patients with a progressive neurodegenerative disease. Here we report on an individual presenting with a multisystem CDG phenotype who was diagnosed with known homozygous pathogenic variants, previously associated with isolated retinitis pigmentosa. An adult Ashkenazi Jewish female developed multiple symptoms of late onset type 1 CDG including seizures, ataxia, protein losing enteropathy, tremor, and titubation in association with elevated mono-oligo/di-oligo transferrin ratio in blood, and classic retinitis pigmentosa. She was diagnosed by whole exome sequencing with the common Ashkenazi Jewish, homozygous p.K42E variants in She was started on Acetazolamide and responded well to the treatment which improved her titubation, tremor, and generalized edema. Reviewing the literature, families with variants and multisystem presentation were different from our patient's presentation in terms of clinical manifestations, severity, genetic defect, and mode of inheritance. In previously reported patients with neurologic symptoms including seizures, movement abnormalities, and global development delay, the phenotype was caused by heterozygous pathogenic variants in . The infant who was reported with a multisystem phenotype and fatal type 1 CDG had compound heterozygosity for a nonsense and a splice site variant in resulting in DHDDS-CDG. The discovery of the novel phenotype associated with the common p.K42E pathogenic variant in expands the spectrum of CDG and further enhances our understanding on the role of in glycosylation beyond the retina.