Congenital disorders of glycosylation: Prevalence, incidence and mutational spectrum in the Polish population

Abstract

Introduction The incidence and prevalence of congenital disorders of glycosylation (CDG) have not been well established. The aim of the study was to evaluate the prevalence, incidence and genotypes of CDG patients diagnosed during the last 23 years in Poland (1997 – 30th October 2020). Material and methods The diagnosis was based on serum Tf IEF which is performed at The Children's Memorial Health Institute (CMHI) in Warsaw. Based on demographic data, the prevalence of CDG among the Polish population in 2020 as well as the birth prevalence of CDG from 1990 to 2020 were estimated. Results 39 patients (from 35 families) with molecularly confirmed CDG were diagnosed, including 17 (44%) patients (from 16 families) with PMM2-CDG. The c.422G > A, p.Arg141His and c.691G > A, p.Val231Met pathogenic missense variants were the most common identified PMM2 variants. Eleven other patients were diagnosed with CDG based on serum Tf IEF analysis only; the molecular analysis is pending. Ten CDG patients died, including 6 with PMM2-CDG, 1 with PGM1-CDG and 1 with DPAGT1-CDG. The prevalence of CDG in the Polish population was estimated at approximately 1 per million while that of PMM2 at 0.4 per million. The annual incidence of CDG was estimated at 0.013 per 100,000 people in 2020. Conclusions A low frequence of CDG in our study could be underestimated.

The Estimated Prevalence of N-Linked Congenital Disorders of Glycosylation Across Various Populations Based on Allele Frequencies in General Population Databases

“…If we exclude FUK-CDG and MAN2B2-CDG, the prevalence in Europeans is slightly lower, one in 24,000. Compared to available data ( Vals et al, 2018 ; Lipinski et al, 2021 ), the expected and observed prevalence differ. The lower observed prevalence might be somewhat underestimated because of undiagnosed patients due to different causes such as unrecognized phenotypes, negative screening results or limited access to different metabolic and molecular studies.…”

“…Mainly at the expense of PMM2-CDG, type 1 defects are more frequently diagnosed than type 2 defects ( Peanne et al, 2017 ; Medrano et al, 2019 ) but compared to PMM2-CDG, other defects occur much seldom. The estimated combined prevalence of CDG among the Saudi population is 14 per million ( Alsubhi et al, 2017 ), whereas, in Poland, the prevalence is approximately one case per million ( Lipinski et al, 2021 ). The worldwide individual prevalence of different defects remains unknown.…”

Congenital Disorders of Glycosylation: What Clinicians Need to Know?

“…After the diagnosis of CDG-I based on serum Tf IEF, phosphomannomutase-2 (PMM2) and phosphomannose isomerase (PMI) activity should be measured in fibroblasts or leukocytes in the proper clinical context (1)(2)(3)(4)85). PMM2-CDG has the best-defined clinical phenotype and is by far the most frequent N-glycan assembly defect (99). PMI activity should be measured in case of clinical and biochemical presentation mainly expressed by the liver.…”

Transferrin gene polymorphisms alter the transferrin focusing pattern, making congenital disorder of glycosylation diagnosis difficult

“…Serum Tf isoforms were analyzed by isoelectrofocusing (IEF) agarose gel electrophoresis according to the modification introduced in our laboratory (Adamowicz et al, 1996;Adamowicz et al, 2007) of the method described by Van Eijk and others (Van Eijk et al, 1982). Since 1995, the CDG selective screening based on serum Tf IEF has been performed at our Institute (CMHI) for patients from the entire country (Bogdańska et al, 2021;Lipiński et al, 2021). During the years of 1995-2020, a total number of 23,183 serum Tf isoform analyses from pediatric patients have been performed.…”