1 - Pediatrics Resident, Pediatric Department, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
2 - Dietetic Service, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
3 - Biochemical Genetics Unit, Centro de Genética Médica Jacinto de Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal
4 - Neuropediatric Service, Pediatric Department, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
5 - Reference Center of Inherited Metabolic Diseases, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
- Poster em 16º Simposio Internacional da Sociedade Portuguesa de Doenças Metabólicas Virtual, 11-13 novembro de 2020
Resumo:
Background: Variants in the SLC35A2 gene (MIM#300896), on the X chromosome, codes for the transporter of UDP-galactose to the Golgi apparatus and results in a N-linked congenital disorder of glycosylation (CDG). The phenotype includes developmental delay, early epileptic encephalopathy with hypsarrhythmia, hypotonia, dysmorphic features, skeletal abnormalities and cortical visual impairment. As some CDGs have been successfully treated with hexose supplementation (e.g., galactose for PGM1-CDG, fucose for SLC35C1-CDG, or mannose for MPI-CDG) it was been considered a possibility in SLC35A2-CDG. The rational is that galactose might be able to increase the cytosolic UDP-galactose concentration and by this way increase galactose transport and use in the Golgi apparatus. We report our experience with a six-month trial of oral D-galactose supplementation in a female patient with SLC35A2-CDG.
Case Report: A 2-year-old female patient with a diagnosis of SLC35A2-CDG, presented at 2 months of age with epileptic encephalopathy with hypsarrhythmia, developmental delay, axial hypotonia, limb hypertonia and slight dysmorphic features. Epilepsy was difficult to control with multiple trials of medication including ACTH, topiramate, vigabatrin and levetiracetam. With the association of ketogenic diet, partial control of seizures was achieved. Due to promising reports on the use of D-galactose, she started on the dose of 1g/Kg/day, 4qid, with adjustments on her ketogenic diet. After six months of supplementation, the mother reported slight improvement in attention, social interaction and head control. Seizures control was difficult to compare as there were temporal increase during respiratory infections. The only side effect reported was transient abdominal pain, without diarrhea. As the patient had several controls with abnormal type 2 transferrin isoelectric focusing (TIEF), it was used as a biomarker for therapy efficacy monitoring. In spite of transferrin glycosylation focusing pattern completely normalized after therapy, no improvements on EEG were noted.
Comments: In our case, oral D-galactose was well tolerated, and improvement in attention, social contact and head control was observed, whilst dubious effect on epilepsy. As reported previously, TIEF completely normalized. Combining galactose supplementation and ketogenic diet was a challenging issue. A longer follow-up is needed to ascertain therapeutic efficacy.