Incidence and prevalence of phosphomannomutase 2-congenital disorder of glycosylation: Past, present, and future

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F25%3A10501938" target="_blank" >RIV/00064165:_____/25:10501938 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10501938

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=g_-I~NShdv" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=g_-I~NShdv</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ymgme.2025.109188" target="_blank" >10.1016/j.ymgme.2025.109188</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Incidence and prevalence of phosphomannomutase 2-congenital disorder of glycosylation: Past, present, and future

Popis výsledku v původním jazyce

Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) accounts for about 60 % of all CDGs and is caused by pathogenic variants of the gene encoding PMM2, which catalyzes an essential early step in N-linked glycosylation. Efforts to derive an accurate prevalence estimate for this often life-threatening disorder, for which there are currently no approved therapies, are hampered by the wide spectrum of clinical manifestations, the rarity of the disease, and the lack of a central global patient registry. Here, we calculated new estimates of PMM2-CDG incidence and prevalence in North America and Europe based on the frequency of disease-causing alleles using the Hardy-Weinberg equation. Allele frequencies were obtained from the Genome Aggregation Database (gnomAD v4.0) and the likelihood of specific allele combinations resulting in a live birth was adjusted based on the occurrence of genotypes in patient datasets and the expected consequences for protein function. New incidence and prevalence estimates were then calculated in the context of historical ethnicity and birth data from national statistical databases, combined with estimated patient mortality rates. The calculated new incidence estimate was 1 in 33,576 for North America and Europe combined (1 in 40,375 and 29,043, respectively), which predicts an average of 303 live births per year for both regions combined since 1980. The new prevalence estimate was 1 in 63,694 (1 in 76,183 and 57,022 in North America and Europe, respectively), which translates to a total of 14,154 patients living with PMM2-CDG in North America and Europe. Notably, this prevalence is more than 5-fold higher than the current estimate of 2447 diagnosed cases combined, and 10-fold higher than the worldwide prevalence most frequently quoted in the literature. These striking differences highlight the underdiagnosis of the disease and the critical need for improved diagnostic and therapeutic strategies for PMM2-CDG.

Název v anglickém jazyce

Incidence and prevalence of phosphomannomutase 2-congenital disorder of glycosylation: Past, present, and future

Popis výsledku anglicky

Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) accounts for about 60 % of all CDGs and is caused by pathogenic variants of the gene encoding PMM2, which catalyzes an essential early step in N-linked glycosylation. Efforts to derive an accurate prevalence estimate for this often life-threatening disorder, for which there are currently no approved therapies, are hampered by the wide spectrum of clinical manifestations, the rarity of the disease, and the lack of a central global patient registry. Here, we calculated new estimates of PMM2-CDG incidence and prevalence in North America and Europe based on the frequency of disease-causing alleles using the Hardy-Weinberg equation. Allele frequencies were obtained from the Genome Aggregation Database (gnomAD v4.0) and the likelihood of specific allele combinations resulting in a live birth was adjusted based on the occurrence of genotypes in patient datasets and the expected consequences for protein function. New incidence and prevalence estimates were then calculated in the context of historical ethnicity and birth data from national statistical databases, combined with estimated patient mortality rates. The calculated new incidence estimate was 1 in 33,576 for North America and Europe combined (1 in 40,375 and 29,043, respectively), which predicts an average of 303 live births per year for both regions combined since 1980. The new prevalence estimate was 1 in 63,694 (1 in 76,183 and 57,022 in North America and Europe, respectively), which translates to a total of 14,154 patients living with PMM2-CDG in North America and Europe. Notably, this prevalence is more than 5-fold higher than the current estimate of 2447 diagnosed cases combined, and 10-fold higher than the worldwide prevalence most frequently quoted in the literature. These striking differences highlight the underdiagnosis of the disease and the critical need for improved diagnostic and therapeutic strategies for PMM2-CDG.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Genetics and Metabolism

ISSN

1096-7192

e-ISSN

1096-7206

Svazek periodika

146

Číslo periodika v rámci svazku

1-2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

109188

Kód UT WoS článku

001586751000001

EID výsledku v databázi Scopus

2-s2.0-105011983861