Natural Killer Cell Receptors and Cytotoxic Activity in Phosphomannomutase 2 Deficiency (PMM2-CDG)

García-López, Roberto; Morena‐Barrio, María Eugenia de la; Alsina, Laia; Pérez‐Dueñas, Belén; Jaeken, Jaak; Serrano, Mercedes; Casado, Mercedes; Hernández‐Caselles, Trinidad

doi:10.1371/journal.pone.0158863

Cited by 9 publications

(9 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study confirmed previously reported infection-related features in PMM2-CDG, namely (1) the higher prevalence of infections during infancy/early childhood; (2) their organ-specific pattern (particularly RT and GI); (3) the not negligible occurrence of sepsis evolving from organ-specific infections and iv) their associated early lethality [ 13 , 14 , 16 , 17 , 52 , 53 ]. All these observations highlight the need for close monitoring until full remission occurs to ensure recovery and to prevent clinical aggravation and fatal outcomes [ 17 ].…”

Section: Discussionsupporting

confidence: 90%

“…Immunological involvement in CDG is an underexplored field. Even though the ubiquitous importance of glycans in the immune system and response is well-established, clear molecular and clinical evidence capable of fully clarifying the immune phenotype of CDG patients, particularly in PMM2-CDG, is lacking [13,14,16,17,[50][51][52]. This lack of knowledge regarding immunological involvement is evidenced in this study by: (i) the~11% of PMM2-CDG patients with unsolved immune status and (ii) the uncertainty or ignorance of PMM2-CDG participants about the presence of specific immune-related manifestations (6.6%, 7.4% and 16.4% related to allergies, infections and autoimmune diseases, respectively).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach

Francisco

Pascoal

Marques‐da‐Silva

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

Congenital disorders of glycosylation (CDG) are rare diseases with variable phenotypes and severity. Immunological involvement remains a largely uncharted topic in CDG, mainly due to lack of robust data. To better characterize immune-related manifestations’ prevalence, relevance, and quality-of-life (QoL) impact, we developed electronic questionnaires targeting (1) CDG patients and (2) the general “healthy” population. Two-hundred and nine CDG patients/caregivers and 349 healthy participants were included in this study. PMM2-CDG was the most represented CDG (n = 122/209). About half of these participants (n = 65/122) described relevant infections with a noteworthy prevalence of those affecting the gastrointestinal tract (GI) (63.1%, n = 41/65). Infection burden and QoL impact were shown as infections correlated with more severe clinical phenotypes and with a set of relevant non-immune PMM2-CDG signs. Autoimmune diseases had only a marginal presence in PMM2-CDG (2.5%, n = 3/122), all being GI-related. Allergy prevalence was also low in PMM2-CDG (33%, n = 41/122) except for food allergies (26.8%, n = 11/41, of PMM2-CDG and 10.8%, n = 17/158, of controls). High vaccination compliance with greater perceived ineffectiveness (28.3%, n = 17/60) and more severe adverse reactions were described in PMM2-CDG. This people-centric approach not only confirmed literature findings, but created new insights into immunological involvement in CDG, namely by highlighting the possible link between the immune and GI systems in PMM2-CDG. Finally, our results emphasized the importance of patient/caregiver knowledge and raised several red flags about immunological management.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach

Francisco

Pascoal

Marques‐da‐Silva

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…In two patients, fever was also associated with pericarditis and vasculitis . Half of the patients reported responded normally to vaccination . Age‐appropriate vaccination is recommended …”

Section: Systems Summaries and Statementsmentioning

confidence: 99%

International clinical guidelines for the management of phosphomannomutase 2‐congenital disorders of glycosylation: Diagnosis, treatment and follow up

Altassan

Péanne

Jaeken

et al. 2019

J of Inher Metab Disea

Self Cite

107

126

View full text Add to dashboard Cite

Phosphomannomutase 2 (PMM2-CDG) is the most common congenital disorder of N-glycosylation and is caused by a deficient PMM2 activity. The clinical presentation and the onset of PMM2-CDG vary among affected individuals ranging from a severe antenatal presentation with multisystem involvement to mild adulthood presentation limited to minor neurological involvement. Management of affected patients requires a multidisciplinary approach. In this article, a systematic review of the literature on PMM2-CDG was conducted by a group of international experts in different aspects of CDG. Our managment guidelines were initiated based on the available evidence-based data and experts' opinions. This guideline mainly addresses the clinical evaluation of each system/organ involved in PMM2-CDG, and the recommended management approach. It is the first systematic review of current practices in PMM2-CDG and the first guidelines aiming at establishing a practical approach to the recognition, diagnosis and management of PMM2-CDG patients.

show abstract

“…The spontaneous closure of ASD is a very complicated process and the mechanism is still unclear, it is generally believed that low weight gain with growth retardation, persistent continuous blood shunting, and delayed development of the cardiac septum may affect this process, causing the exacerbation of ASD [ 13 ]. Immune dysfunction and failure to thrive are both common in patients with CDG-1a [ 14 ]. In our patient, immune dysfunction and failure to thrive occurred at an early stage and persisted in the whole course of the disease.…”

Section: Discussionmentioning

confidence: 99%

Atrial septal defect in a patient with congenital disorder of glycosylation type 1a: a case report

Tang

et al. 2018

J Med Case Reports

View full text Add to dashboard Cite

BackgroundAtrial septal defect often become more severe when encountered in genetic syndromes. Congenital disorder of glycosylation type 1a is an inherited metabolic disorder associated with mutations in PMM2 gene and can affect almost all organs. Cardiac abnormalities vary greatly in congenital disorder of glycosylation type 1a and congenital heart defects have already been reported, but there is little knowledge about the effect of this inherited disorder on an existing congenital heart defect. Herein we report for the first time on a baby with congenital disorder of glycosylation type 1a with atrial septal defect and make a comparison of changes in atrial septal defect by follow-ups to the age of 3.Case presentationOur patient was an 8-month-old Han Chinese boy. At the initial visit, he presented with recurrent lower respiratory infection, heart murmur, psychomotor retardation, inverted nipples, and cerebellar atrophy. Echocardiography revealed a 8 mm secundum atrial septal defect with left-to-right shunt (Qp/Qs ratio 1.6). Enzyme testing of phosphomannomutase 2 demonstrated decreased levels of phosphomannomutase 2 activities in fibroblasts. Whole exon sequencing showed he was heterozygous for a frameshift mutation (p.I153X) and a missense mutation (p.I132T) in PMM2 gene. The diagnosis of congenital disorder of glycosylation type 1a with atrial septal defect was issued. Now, he is 3-years old at the time of this writing, with the development of congenital disorder of glycosylation type 1a (cerebellar atrophy become more severe and the symptom of nystagmus emerged), the size of atrial septal defect increased to 10 mm and the Qp/Qs ratio increased to 1.9, which suggested exacerbation of the atrial septal defect. Congenital heart defect-associated gene sequencing is then performed and shows there are no pathogenic mutations, which suggested intrinsic cardiac factors are not the cause of exacerbation of the atrial septal defect in our patient and it is reasonable to assume congenital disorder of glycosylation type 1a can worsen the situation of the existing atrial septal defect.ConclusionsThis report highlights the view that congenital disorders of glycosylation type 1a should be excluded when faced with congenital heart defect with cerebellar atrophy or neurodevelopmental delay, especially when the situation of congenital heart defect becomes more and more severe.

show abstract

Natural Killer Cell Receptors and Cytotoxic Activity in Phosphomannomutase 2 Deficiency (PMM2-CDG)

Cited by 9 publications

References 43 publications

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach

International clinical guidelines for the management of phosphomannomutase 2‐congenital disorders of glycosylation: Diagnosis, treatment and follow up

Atrial septal defect in a patient with congenital disorder of glycosylation type 1a: a case report

Contact Info

Product

Resources

About