Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II

Teneiji, Amal Al; Bruun, Theodora; Sidky, Sarah; Cordeiro, Dawn; Cohn, Ronald D.; Mendoza-Londoño, Roberto; Moharir, Mahendranath; Raiman, Julian; Siriwardena, Komudi; Kyriakopoulou, Lianna; Mercimek-Mahmutoglu, Saadet

doi:10.1016/j.ymgme.2016.12.014

Cited by 46 publications

(50 citation statements)

References 43 publications

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“…PMM2-CDG was the most common (40%) CDG identified in our study, similarly to the literature [16][17]. Among the N-hypoglycosylation disorders, ALG6-CDG is reported as the second, while ALG1-CDG as the third most frequent type [18].…”

Section: Discussionsupporting

confidence: 86%

Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up

Bogdańska

Lipiński

Szymańska-Rożek

et al. 2020

Preprint

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Background: Congenital disorders of glycosylation (CDG) result from defects in the synthesis of glycans and the attachment of glycans to proteins and lipids. Our study aimed to describe the clinical, biochemical and molecular findings of CDG patients, and to present the long-term follow-up. Material and methods: A single-centre study (1995-2019 years) of patients with congenital disorders of N-glycosylation and combined N- and O-hypoglycosylation, diagnosed based on the serum transferrin (Tf) and apolipoprotein C-III (apoC-III) isoforms analysis, and confirmed molecularly, was performed. Results: Among 32 patients included into the study, 24 had type I Tf isoform profile, in 12 of them deficient PMM2 activity was detected. Three patients were diagnosed with ALG13-CDG; serum Tf isoform profile was normal in one of them, in one other was indicative for type I. Four patients had type II Tf isoform profile. The phenotypic and genotypic spectrum of 32 patients with CDG during long-term (in some cases over 20 years) observation was characterised and several measurements of serum Tf isoforms taken. Statistical analysis revealed strong negative correlation between Asialo-Tf and Tetrasialo-Tf, as well as between Disialo-Tf and Tetrasialo-Tf. Positive correlation was shown between Tetrasialo-Tf and Penasialo-Tf. Within type I CDG, no difference in % Tf isoforms was revealed between PMM2-CDG and non-PMM2-CDG patients. However, these two groups differed significantly in the such diagnostic features as: cerebellar ataxia, failure to thrive, hypothyroidism, pericardial effusion, cardiomyopathy, inverted nipples, prolonged INR. The effect of treatment with mannose in 2 patients with MPI-CDG were assesed and we found that % of Asialo-Tf, Monosialo-Tf, and Disialo-Tf was significanty lowered, whereas Tetrasialo- Tf and Pentasialo-Tf rose, coming closer or falling into the reference range. Conclusions: The novel finding was an abnormal Tf IEF pattern in two ALG13-CDG patients and normal in one ALG1-CDG patient. Clinical manifestation of presented CDG patients was similar to that reported in the literature. Mannose supplementation in MPI-CDG patients, as well as galactose supplementation in PGM-CDG patient improved patients’ clinical picture and Tf isoform profiles.

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Section: Discussionsupporting

confidence: 86%

Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up

Bogdańska

Lipiński

Szymańska-Rożek

et al. 2020

Preprint

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“…To date, only 10 patients have been described with ALG11‐CDG (OMIM# 613661) (Al Teneiji et al, ; Pereira et al, ; Regal et al, ; Rind et al, ; Thiel et al, ). We report two additional unrelated patients to expand the ALG11‐CDG phenotype to include normal transferrin glycosylation as determined by mass spectrometry in one individual, together with functional studies supporting the pathogenicity of their novel ALG11 mutations.…”

Section: Introductionmentioning

confidence: 99%

ALG11‐CDG syndrome: Expanding the phenotype

Haanpää

Gallant

et al. 2019

American J of Med Genetics Pt A

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ALG11‐Congenital Disorder of Glycosylation (ALG11‐CDG, also known as congenital disorder of glycosylation type Ip) is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation. We describe two unrelated patients with ALG11‐CDG due to novel mutations, review the literature of previously described affected individuals, and further expand the clinical phenotype. Both affected individuals reported here had severe psychomotor disabilities and epilepsy. Their fibroblasts synthesized truncated precursor glycan structures, consistent with ALG11‐CDG, while also showing hypoglycosylation of a novel biomarker, GP130. Surprisingly, one patient presented with normal transferrin glycosylation profile, a feature that has not been reported previously in patients with ALG11‐CDG. Together, our data expand the clinical and mutational spectrum of ALG11‐CDG.

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“…Two CDG have been significantly associated with deafness namely RFT1-CDG (10 out of 13 patients) (Aeby et al 2016,B a r b a et al 2016, Jaeken et al 2009, Ondruskova et al 2012, Pérez-Cerdá et al 2017) and ALG11-CDG (4/9) (Régal et al 2015,Rindetal.2010, Thiel et al 2012. Upon review of the literature describing cases of PMM2-CDG, we found 15 reports with altogether 20 patients showing sensorineural hearing loss/hearing impairment (Al Teneiji et al 2017,B a r o n e et al ,Ennsetal.2002,Feracoetal.2012,GarciaSilva et al 1996, Gehrmann et al 2003, Horslen et al 1991, Hutchesson et al 1995, Imtiaz et al 2000, Kjaergaard et al 2001,Kristianssonetal.1989, Messenger et al 2014, Szlago et al 2006van de Kamp et al 2007, Veneselli et al 1998). There is no correlation between the severity of the phenotype and hearing impairment; PMM2-CDG patients with hearing loss survived between 6 weeks and at least 24 years.…”

Section: Dear Editormentioning

confidence: 87%