Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature.

Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a multisystem inborn error of metabolism. To better characterise the natural history of PMM2-CDG. Medical charts of 96 patients with PMM2-CDG (86 families, 41 males, 55 females) were retrospectively reviewed. Data on clinical, laboratory and molecular parameters at diagnosis were analysed. Follow-up data at last examination were reported for 25 patients. The patients were born between 1963 and 2011. Diagnosis of PMM2-CDG was made at a mean (SD) age of 6.8 (8.5) years. The presenting signs were mostly neurological (hypotonia, intellectual disability, cerebellar syndrome) and observed in almost all the patients. A total of 38 patients (14 males, 24 females) exhibited, in addition to neurological signs, visceral features including at least one of these: feeding difficulty requiring a nutritional support (n=23), cardiac features (n=20; pericarditis: 14, cardiac malformation: 9, cardiomyopathy: 2), hepato-gastrointestinal features (n=12; chronic diarrhoea: 7, protein-losing enteropathy: 1, ascites: 3, liver failure: 1, portal hypertension: 1), kidney features (n=4; nephrotic syndrome: 2, tubulopathy: 2) and hydrops fetalis (n=1). Twelve patients died at a mean age of 3.8 years (especially from pericarditis and other cardiac issues). Laboratory abnormalities mostly included elevated transaminases and abnormal coagulation parameters. High thyreostimulin levels, hypocholesterolemia, hypoalbuminemia and elevated transaminases were associated with the visceral phenotype. Besides the common Arg141His PMM2 variant harboured by half of the patients, 45 different variants were observed. PMM2-CDG clinical phenotype is heterogeneous in terms of clinical course, with no clear division between neurological and visceral presentations.

Schiff M ，Roda C ，Monin ML ，Arion A ，Barth M ，Bednarek N ，Bidet M ，Bloch C ，Boddaert N ，Borgel D ，Brassier A ，Brice A ，Bruneel A ，Buissonnière R ，Chabrol B ，Chevalier MC ，Cormier-Daire V ，De Barace C ，De Maistre E ，De Saint-Martin A ，Dorison N ，Drouin-Garraud V ，Dupré T ，Echenne B ，Edery P ，Feillet F ，Fontan I ，Francannet C ，Labarthe F ，Gitiaux C ，Héron D ，Hully M ，Lamoureux S ，Martin-Coignard D ，Mignot C ，Morin G ，Pascreau T ，Pincemaille O ，Polak M ，Roubertie A ，Thauvin-Robinet C ，Toutain A ，Viot G ，Vuillaumier-Barrot S ，Seta N ，De Lonlay P ... -  《-》

29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype.

Monin ML ，Mignot C ，De Lonlay P ，Héron B ，Masurel A ，Mathieu-Dramard M ，Lenaerts C ，Thauvin C ，Gérard M ，Roze E ，Jacquette A ，Charles P ，de Baracé C ，Drouin-Garraud V ，Khau Van Kien P ，Cormier-Daire V ，Mayer M ，Ogier H ，Brice A ，Seta N ，Héron D ... -  《Orphanet Journal of Rare Diseases》

The Analysis of Variants in the General Population Reveals That PMM2 Is Extremely Tolerant to Missense Mutations and That Diagnosis of PMM2-CDG Can Benefit from the Identification of Modifiers.

Citro V ，Cimmaruta C ，Monticelli M ，Riccio G ，Hay Mele B ，Cubellis MV ，Andreotti G ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Renal involvement in PMM2-CDG, a mini-review.

Phosphomannomutase 2 deficiency (PMM2-CDG) is the most common N-linked glycosylation disorder. The majority of patients present with a multisystem phenotype, including central nervous system involvement, hepatopathy, gastrointestinal and cardiac symptoms, endocrine dysfunction and abnormal coagulation. Renal abnormalities including congenital malformations and altered renal function are part of the multisystem manifestations of congenital disorders of glycosylation. We reviewed the literature on 933 patients with molecularly and/or enzymatically confirmed PMM2 deficiency to evaluate the incidence of renal involvement in PMM2-CDG. Renal abnormalities were reported in 56 patients. Congenital abnormalities were present in 41 out of these 55. Cystic kidney and mild proteinuria were the most common findings. One of the most severe renal manifestations, congenital nephrotic syndrome, was detected in 6 children. Renal manifestations were not associated with the presence of specific PMM2 alleles. This review summarizes the reported renal abnormalities in PMM2-CDG and draws attention to the pathophysiological impact of abnormal glycosylation on kidney structure and function.

Altassan R ，Witters P ，Saifudeen Z ，Quelhas D ，Jaeken J ，Levtchenko E ，Cassiman D ，Morava E ... -  《-》

PMM2-CDG: phenotype and genotype in four affected family members.

Congenital disorders of glycosylation (CDG) are genetic defects in protein and lipid glycosylation. PMM2-CDG is the most prevalent protein N-glycosylation disorder with more than 700 reported patients. Here we report on a large Italian family with four affected members and three mutations. Two young sisters are compound heterozygous for mutations p.Leu32Arg and p.Arg141His, while two paternal great-aunts are compound heterozygosity for p.Leu32Arg and p.Thr237Met. The latter association has not been reported before. The most severely affected member had in addition an ALG6 mutation known to exacerbate the phenotype of patients with PMM2-CDG.

Bortot B ，Cosentini D ，Faletra F ，Biffi S ，De Martino E ，Carrozzi M ，Severini GM ... -  《-》