Congenital disorder of glycosylation : clinical case study of patients harboring pathogenic mutations in phosphomannomutase 2 gene (PMM2-CDG)

Background Congenital disorders of glycosylation (CDG) is a heterogeneous group of rare heritable disorders, PMM2-CDG being the most common form, caused by pathogenic variants in the gene encoding phosphomannomutase-2 (PMM2) enzyme imposing challenges due to highly variable, multisystemic manifestations of the disorder. Objective The study presents two clinical cases of PMM2-CDG along with their clinical manifestations to emphasize the role of genetic diagnosis for timely implementation of therapy. Method: Based on the clinical phenotypes, the patients were advised to undergo NGS-based whole exome sequencing and were evaluated for any pathological variants in the genes related to the phenotype. Result Our case study involved two male patients, aged 7 and 1 respectively, born to parents having consanguinity as a part of their family history. They both presented with clinical indications of global developmental delay, ocular involvement, malformed ears and seizures. The MRI images of the patient aged 1 showed cerebellar atrophy with cerebellar hyperintensities. In both the cases, homozygous missense mutations were identified in the PMM2 gene: exon 5 c.385G>A (p.Val129Met) for the first patient and exon 8 c.710C>T (p.Thr237Met) for the second respectively. Conclusion Both these clinical variants identified, have been previously reported and associated with congenital disorder of N-glycosylation type Ia. PMM2-CDG is an autosomal recessive disorder and hence, parental screening was recommended to parents for identifying the carrier status, to further minimize the risk of occurrence in subsequent pregnancies. Importance of continuous monitoring of the arising cardiac, ophthalmologic and renal issues for symptom based supportive treatment was highlighted.