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

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

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01657-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Anna Bogdańska ◽

Patryk Lipiński ◽

Paulina Szymańska-Rożek ◽

Aleksandra Jezela-Stanek ◽

Dariusz Rokicki ◽

...

Keyword(s):

Failure To Thrive ◽

Congenital Disorders ◽

Type I ◽

Congenital Disorders Of Glycosylation ◽

Diagnostic Features ◽

Strong Negative Correlation ◽

Single Center Study ◽

Long Term Follow Up

Abstract 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.

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P0574 LONG TERM FOLLOW UP OF CONGENITAL DISORDERS OF GLYCOSYLATION TYPE I OR CDG I SYNDROME

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/00005176-200406001-00698 ◽

2004 ◽

Vol 39 (Supplement 1) ◽

pp. S275

Author(s):

C. Lenaerts ◽

D. H??ron ◽

V. Cormier ◽

G. Morin ◽

M. Mathieu ◽

...

Keyword(s):

Congenital Disorders ◽

Type I ◽

Congenital Disorders Of Glycosylation ◽

Long Term Follow Up

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Liver Involvement in Congenital Disorders of Glycosylation and Deglycosylation

Frontiers in Pediatrics ◽

10.3389/fped.2021.696918 ◽

2021 ◽

Vol 9 ◽

Author(s):

Patryk Lipiński ◽

Anna Bogdańska ◽

Piotr Socha ◽

Anna Tylki-Szymańska

Keyword(s):

Liver Disease ◽

Elevated Serum ◽

Protein S ◽

Liver Involvement ◽

Congenital Disorders ◽

Congenital Disorders Of Glycosylation ◽

Long Term Follow Up ◽

Serum Transaminases

Background: Congenital disorders of glycosylation (CDG) and NGLY1-CDDG (NGLY1-congenital disorder of deglycosylation) usually represent multisystem (especially neurovisceral) diseases with liver involvement reported in some of them. The aim of the study was to characterize the liver phenotype in CDG and NGLY1-CDDG patients hospitalized in our Institute, and to find the most specific features of liver disease among them.Material and Methods: The study involved 39 patients (from 35 families) with CDG, and two patients (from two families) with NGLY1-CDDG, confirmed molecularly, for whom detailed characteristics of liver involvement were available. They were enrolled based on the retrospective analysis of their medical records.Results: At the time of the first consultation, 13/32 patients were diagnosed with hepatomegaly; none of them with splenomegaly. As many as 23/32 persons had elevated serum transaminases, including 16 (70%) who had mildly elevated levels. During the long-term follow-up (available for 19 patients), serum transaminases normalized in 15/19 (79%) of them, including a spontaneous normalization in 12/15 (80%) of them. The GGT activity was observed to be normal in all study cases. Protein C, protein S and antithrombin activities in plasma were observed in 16 patients, and they were decreased in all of them.Conclusions: It is necessary to conduct a long-term follow-up of liver disease in CDG to obtain comprehensive data.

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Long-term follow-up of patients with Bartter syndrome type I and II

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfq119 ◽

2010 ◽

Vol 25 (9) ◽

pp. 2976-2981 ◽

Cited By ~ 30

Author(s):

E. Puricelli ◽

A. Bettinelli ◽

N. Borsa ◽

F. Sironi ◽

C. Mattiello ◽

...

Keyword(s):

Bartter Syndrome ◽

Type I ◽

Syndrome Type ◽

Long Term Follow Up

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Long-term follow-up of a girl with oro-facio-digital syndrome type I due to a mutation in the OFD 1 gene

Annales de Génétique ◽

10.1016/s0003-3995(02)01116-4 ◽

2002 ◽

Vol 45 (2) ◽

pp. 59-62 ◽

Cited By ~ 9

Author(s):

C. Stoll ◽

P. Sauvage

Keyword(s):

Type I ◽

Syndrome Type ◽

Long Term Follow Up

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Long Term Follow-Up of 103 Untreated Adult Patients with Type 1 Gaucher Disease

Journal of Clinical Medicine ◽

10.3390/jcm8101662 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1662 ◽

Cited By ~ 10

Author(s):

Dinur ◽

Zimran ◽

Becker-Cohen ◽

Arkadir ◽

Cozma ◽

...

Keyword(s):

Gaucher Disease ◽

Substrate Reduction Therapy ◽

Type I ◽

Specific Therapy ◽

Substrate Reduction ◽

Long Term Follow Up ◽

Disease Specific

The introduction of disease-specific therapy for patients with type I Gaucher disease (GD1) was a revolution in the management of patients, but not without cost. Thus, the management of mildly affected patients is still debated. We herein report a long-term follow-up (median (range) of 20 (5–58) years) of 103 GD1 patients who have never received enzymatic or substrate reduction therapy. The median (range) platelet count and hemoglobin levels in last assessment of all but six patients who refused therapy (although recommended and approved) were 152 (56–408) × 103/mL and 13.1 (7.6–16.8) g/dL, respectively. Most patients had mild hepatosplenomegaly. Nine patients were splenectomized. No patient developed clinical bone disease. The median (range) lyso-Gb1 levels at last visit was 108.5 (8.1–711) ng/mL; lowest for patients with R496H/other and highest for patients refusing therapy. This rather large cohort with long follow-up confirms that mildly affected patients may remain stable for many years without GD-specific therapy. The challenge for the future, when newborn screening may detect all patients, is to be able to predict which of the early diagnosed patients is at risk for disease-related complications and therefore for early treatment, and who may remain asymptomatic or minimally affected with no need for disease-specific therapy.

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Treatment and Patient Reported Outcome in Children with Hirschsprung Disease and Concomitant Congenital Heart Disease

BioMed Research International ◽

10.1155/2017/1703483 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Johan Hasserius ◽

Josefine Hedbys ◽

Christina Graneli ◽

Kristine Hagelsteen ◽

Pernilla Stenström

Keyword(s):

Congenital Heart Disease ◽

Congenital Heart ◽

Hirschsprung Disease ◽

Failure To Thrive ◽

Bowel Function ◽

Patient Characteristics ◽

Patient Reported ◽

Long Term Follow Up

Purpose. Congenital heart disease (CHD) is reported to be associated with Hirschsprung disease (HD). The aim was to evaluate any differences between children with HD with and without CHD, respectively, with regard to patient characteristics, medical care, and patient reported bowel function. Method. This is a retrospective chart study and a cross-sectional long-term follow-up of patients older than 4 years old, including all children with HD operated on with transanal endorectal pull-through (TERPT) at a tertiary center of pediatric surgery. Information about patient characteristics, diagnostics, surgery, and medical care was compiled. At long-term follow-up, bowel function was assessed by Bowel Function Score. Results. Included were 53 HD-patients, 13 with CHD and 40 without CHD. Children with CHD more commonly presented with failure to thrive; 4 (23%) compared to those without CHD (0%) (p<0.01). In the long-term follow-up, including 32 patients (6 with CHD), constipation was more commonly reported by children with CHD 5 (83%) than by children without CHD 4 (27%) (p=0.01). No differences were shown in the other parameters such as fecal control and incontinence. Conclusion. HD-patients with CHD more commonly presented with failure to thrive and more frequently reported constipation than HD-patients without CHD. The findings indicate that HD-patients with CHD might need special consideration in their initial care and long-term follow-up.

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