bims-meglyc 2024-10-27 papers

Issue of 2024–10–27
two papers selected by
Silvia Radenkovic, UMC Utrecht

Mol Genet Metab Rep. 2024 Dec;41 101145

Review and metabolomic profiling of unsolved case reveals newly reported autosomal dominant congenital disorder of glycosylation, type Iw formerly thought to only be an autosomal recessive condition.

Undiagnosed Diseases Network

Autosomal dominant congenital disorder of glycosylation (CDG) type Iw (OMIM# 619714) is caused by a heterozygous mutation in the STT3A gene. Most CDGs have an autosomal recessive (AR) mode of inheritance, but several cases with an autosomal dominant (AD) form of an AR CDG have been recently identified. This report describes a 17-year-old male who was referred to the Undiagnosed Diseases Network (UDN) with a history of macrocephaly, failure to thrive, short stature, epilepsy, autism, attention-deficit/hyperactivity disorder, mild developmental delay, intermittent hypotonia, dysmorphic features, and mildly enlarged aortic root. Trio exome sequencing was negative. His biochemical workup included normal plasma amino acids, ammonia, acylcarnitine profile and urine organic and amino acids. His UDN genome sequencing (GS) identified a previously unreported de novo STT3A variant (c.1631A > G: p.Asn544Ser). This variant removes a glycosylation site and was predicted to be destabilizing by structural biology modeling. The patient was formally diagnosed by the UDN Metabolomics Core as having an abnormal transferrin profile indicative of CDG type Iw through metabolomic profiling. We report here an affected male with phenotypic, molecular, and metabolic findings consistent with CDG type Iw due to a heterozygous STT3A variant. This case highlights the importance of further testing of individuals with the phenotypic and metabolic findings of an AR disorder who are heterozygous for a single disease-causing allele and can be shown to have a new AD form of the disorder that represents clinical heterogeneity.

Keywords: Congenital disorders of glycosylation (CDGs); STT3A; Undiagnosed diseases network (UDN)

DOI: https://doi.org/10.1016/j.ymgmr.2024.101145

Res Involv Engagem. 2024 Oct 23. 10(1): 107

A community-centric model for conference co-creation: the world conference on CDG for patients, families and professionals.

Rita Francisco, Carlota Pascoal, Pedro Granjo, Claudia de Freitas, Paula A Videira, Vanessa Dos Reis Ferreira.

BACKGROUND: Patient and public co-creation and involvement in health initiatives have been witnessing great expansion in recent years. From healthcare to research settings, collaborative approaches are becoming increasingly prevalent and diverse, especially in the field of rare diseases which faces complex challenges. Conference development and implementation, however, have been primarily guided by passive, information-sharing models. There is a need for conferences to evolve towards more inclusive, interactive, collaborative, and problem-solving platforms. Here, we aimed to report on a pioneer model, emphasizing a community partnership approach to conference co-creation that takes the World Conference on Congenital Glycosylation Disorders (CDG) as an exemplary case.
METHODS: To answer the need to overcome the lack of access to high-quality information which limits CDG diagnosis, research and treatment options, the World CDG Organization has been refining a community-centric model for conference co-creation. Focusing on the 5th edition of the conference, data on stakeholders' preferences was collected using an online survey and a poll to define the conference agenda, guide its development and select optimal dates for an all-stakeholder inclusive, relevant and participatory event.
RESULTS: We describe the complexities of the community-centric conference co-creation model, detailing its refined methodology and the outcomes achieved. The model is grounded on a participative approach to promote people-centered research and care for CDG patients. The involvement of the public in the conference co-creation and in participatory methods allowed the generation of knowledge on community needs and preferences.
CONCLUSION: This paper describes a reliable, highly adaptable conference co-creation model that fosters community-building, disseminates understandable information, and serves as a borderless platform to incentivize multiple stakeholder collaborations towards CDG research and drug development. We argue this is a reproducible model that can be endorsed and more widely adopted by other disease communities and events.

Keywords: Co-creation; Community centricity; Congenital disorders of Glycosylation; Patient and public involvement (PPI)

DOI: https://doi.org/10.1186/s40900-024-00641-8