Novel Treatment for Congenital Disorder of Glycosylation in a Patient with Novel Homozygote Mutation of PMM2: A Case Report and Review Literature

Abstract

Background: In Congenital Disorder of Glycosylation (CDG) type Ia, homozygous mutations of the PMM2 gene cause phosphomannomutase 2 dysfunction.

Case presentation: Herein, a 10-month-old girl, is presented with severe hypotonia, along with inappropriately normal mental status and normal facies. High 2-ketoglutaric acid was detected in her urine, therefore, the diagnosis of 2-Ketoglutarate dehydrogenase complex (KDHC) deficiency was made for this patient. A high dose of vitamin B1 was administered because thiamine is considered a co-factor in this inborn error of metabolism. She responded very well to the daily administration of 500 mg/day vitamin B1 and stood up without help 5 months later. She had also experienced a seizure, which responded well to pyridoxine. Then, she grew up into a 3.5-years-old child who could talk and walk normally. Recently, whole-exome sequencing was performed for her, which showed homozygote mutation of PMM2, therefore, the diagnosis was changed from KDHC deficiency to PMM2-CDG.

Conclusion: Paying attention to the pathophysiology of inborn errors of metabolism is necessary while considering the defective enzyme co-factor, which may help us to find an option for the treatment of such rare diseases.

Keywords: 2-ketoglutaric aciduria; Congenital Disorder of Glycosylation Ia; PMM2 mutation; Phosphomannomutase; Pyridoxine; Thiamine; Whole Exome Sequencing.