Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up.
Congenital disorders of glycosylation
Follow-up
Glycosylation
Serum transferrin isoforms
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
06 01 2021
06 01 2021
Historique:
received:
20
08
2020
accepted:
21
12
2020
entrez:
7
1
2021
pubmed:
8
1
2021
medline:
22
6
2021
Statut:
epublish
Résumé
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. A single-center study (1995-2019 years) of patients with congenital disorders of N-glycosylation and combined N- and O-hypoglycosylation was performed. Among 32 patients included into the study, there were 12 PMM2-CDG, 3 ALG13-CDG, 3 ALG1-CDG, 1 ALG3-CDG, 3 MPI-CDG, 1 PGM1-CDG, 4 SRD5A3-CDG, 1 DPAGT1-CDG, 3 ATP6AP1-CDG, 1 ATP6V0A2-CDG. The phenotypic and genotypic spectrum 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. Within CDG type I, no difference in % Tf isoforms was revealed between PMM2-CDG and non-PMM2-CDG patients. However, these two groups differed significantly in 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 was assessed and we found that % of asialo-Tf, monosialo-Tf, and disialo-Tf was significantly lowered, whereas tetrasialo-Tf and pentasialo-Tf rose, coming closer or falling into the reference range. 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 PGM1-CDG patient, improved patients' clinical picture and Tf isoform profiles.
Sections du résumé
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-center study (1995-2019 years) of patients with congenital disorders of N-glycosylation and combined N- and O-hypoglycosylation was performed.
RESULTS
Among 32 patients included into the study, there were 12 PMM2-CDG, 3 ALG13-CDG, 3 ALG1-CDG, 1 ALG3-CDG, 3 MPI-CDG, 1 PGM1-CDG, 4 SRD5A3-CDG, 1 DPAGT1-CDG, 3 ATP6AP1-CDG, 1 ATP6V0A2-CDG. The phenotypic and genotypic spectrum 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. Within CDG type I, no difference in % Tf isoforms was revealed between PMM2-CDG and non-PMM2-CDG patients. However, these two groups differed significantly in 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 was assessed and we found that % of asialo-Tf, monosialo-Tf, and disialo-Tf was significantly 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 PGM1-CDG patient, improved patients' clinical picture and Tf isoform profiles.
Identifiants
pubmed: 33407696
doi: 10.1186/s13023-020-01657-5
pii: 10.1186/s13023-020-01657-5
pmc: PMC7789416
doi:
Substances chimiques
ATP6AP1 protein, human
0
ALG3 protein, human
EC 2.4.1.-
Mannosyltransferases
EC 2.4.1.-
Vacuolar Proton-Translocating ATPases
EC 3.6.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
17Références
Eur J Pediatr. 1996 Apr;155(4):347-8
pubmed: 8777936
Semin Neurol. 2014 Jul;34(3):357-66
pubmed: 25192513
Mol Genet Metab. 2017 Mar;120(3):235-242
pubmed: 28122681
Brain Dev. 2017 Apr;39(4):366-367
pubmed: 27923528
N Engl J Med. 2014 Feb 6;370(6):533-42
pubmed: 24499211
Mol Genet Metab. 2018 Mar;123(3):292-296
pubmed: 29229467
J Med Genet. 2017 Dec;54(12):843-851
pubmed: 28954837
Orphanet J Rare Dis. 2014 Dec 11;9:207
pubmed: 25497157
Hum Mol Genet. 2002 Sep 15;11(19):2331-9
pubmed: 12217961
J Inherit Metab Dis. 2020 Mar;43(2):223-233
pubmed: 31420886
JIMD Rep. 2016;27:93-9
pubmed: 26453362
Eur J Med Genet. 2018 Nov;61(11):643-663
pubmed: 29079546
J Clin Endocrinol Metab. 1995 Dec;80(12):3744-9
pubmed: 8530628
J Inherit Metab Dis. 2020 Jul;43(4):671-693
pubmed: 32266963
Orphanet J Rare Dis. 2015 Oct 26;10:138
pubmed: 26502900
J Clin Invest. 2000 Jan;105(2):233-9
pubmed: 10642602
J Inherit Metab Dis. 2017 Sep;40(5):657-672
pubmed: 28726068
Eur J Med Genet. 2020 Jun;63(6):103881
pubmed: 32058063
Am J Hum Genet. 1998 Jun;62(6):1535-9
pubmed: 9585601
Brain. 2010 Nov;133(11):3210-20
pubmed: 20852264
Hum Mutat. 2000 Nov;16(5):386-94
pubmed: 11058895
Nat Commun. 2016 May 27;7:11600
pubmed: 27231034
J Pediatr. 2017 Apr;183:170-177.e1
pubmed: 28139241
Eur J Hum Genet. 2018 May;26(5):618-621
pubmed: 29192153
Clin Chem. 2003 Nov;49(11):1839-45
pubmed: 14578315
Clin Genet. 2019 May;95(5):615-626
pubmed: 30653653
J Inherit Metab Dis. 2011 Aug;34(4):907-16
pubmed: 21431621
J Inherit Metab Dis. 2017 Mar;40(2):195-207
pubmed: 28108845
J Inherit Metab Dis. 2019 Jan;42(1):5-28
pubmed: 30740725
Cell. 2010 Jul 23;142(2):203-17
pubmed: 20637498
Clin Chim Acta. 1982 May 20;121(2):209-16
pubmed: 7094339
J Inherit Metab Dis. 2018 May;41(3):541-553
pubmed: 29654385
J Inherit Metab Dis. 2007 Jun;30(3):407
pubmed: 17457694
Mol Genet Metab. 2019 Jan;126(1):1-5
pubmed: 30454869
FEBS Lett. 1995 Dec 27;377(3):318-20
pubmed: 8549746
Annu Rev Neurosci. 2015 Jul 8;38:105-25
pubmed: 25840006
Mol Genet Metab. 2018 Mar;123(3):364-374
pubmed: 29396028