Multiorgan involvement and genetic spectrum of 20 Chinese patients with PMM2-CDG

The most common congenital disorders of glycosylation (CDG) is the phosphomannomutase 2 (PMM2) deficiency (PMM2-CDG). PMM2-CDG is a complex genetic disorder that often found in infancy or early childhood with a clinically heterogeneous variety of neurological and non- neurological symptoms. To expand the phenotypic and genetic spectrum of PMM2-CDG, we summarized the characteristics of 20 Chinese patients.

All patients were diagnosed by genetic analysis. Clinical characteristics, genotypes, imaging, electrophysiological, and metabolic data were analyzed retrospectively.

Twelve males and eight females with PMM2-CDG were included. The median age at diagnosis was 12.0 (ranging from 6.0 to 52.0) months, while the median age at final follow-up was 10.3 (ranging from 5.1 to 12.8) years. All patients exhibited multisystem symptoms and various neurological symptoms were observed. Developmental delay was the primary initial symptoms. Dystaxia, growth retardation and liver damage were also common phenotypes. Cerebellar atrophy was the characteristic abnormality on brain imaging. Fourteen variants of the PMM2 gene were identified, of which five, c.82A > G (p.M28V), c.551C > T (p. P184L), c.640G > T (p.G214C), c.656A > T (p.E219V) and c.712C > G (p.R238G), were newly reported. The most prevalent variant was c.430 T > C (p.F144L), which was identified in 65.0 % of patients, followed by c.395 T > C (p.I132T). Consistent with reports from other populations, missense variants constituted the predominant type of PMM2 gene alterations.

PMM2-CDG presents as a multi-system disease with diverse clinical phenotypes, posing challenges to early identification and diagnosis. The most common pathogenic variant in this Chinese cohort was c.430 T > C (p.F144L), which is close to, but different from, the common pathogenic variant c.422G > A (p.R141H) among European PMM2-CDG patients.