bims-meglyc 2024-09-29 papers

Issue of 2024‒09‒29
two papers selected by
Silvia Radenkovic, UMC Utrecht

Mol Genet Genomic Med. 2024 Sep;12(9): e70010

Rebecca Finnegan, Mary O'Regan, Máire White, Gianpiero L Cavalleri, Norman Delanty, Katherine A Benson, Marie T Greally.

BACKGROUND: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG-1 syndromes, most of which are inherited as autosomal recessive traits, although X-linked inheritance has also been reported. Pathogenic variants in the asparagine-linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36). The NM_001099922.3:c.320A>G; p.(Asn107Ser) variant is the most frequently described pathogenic variant in ALG13, with 59 females and 2 males with this variant reported to date.METHODS: We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant.
RESULTS: All three males have a de novo mutation, infantile spasms, DEE, drug-resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13.
CONCLUSION: The similarity of phenotype in the three males with the c.320A>G variant in ALG13, suggests a possible genotype-phenotype correlation.

Keywords: ALG13 gene; ALG13‐CDG; DEE36; X‐chromosome inactivation; genotype–phenotype correlation

DOI: https://doi.org/10.1002/mgg3.70010

Mol Genet Metab. 2024 Sep 14. pii: S1096-7192(24)00463-3. [Epub ahead of print]143(1-2): 108579

Standardized emergency protocols to improve the management of patients with suspected or confirmed inherited metabolic disorders (IMDs): An initiative of the French IMDs Healthcare Network for Rare Diseases.

OBJECTIVES: Patients with inherited metabolic disorders (IMDs) may require emergency hospital care to prevent life-threatening situations such as metabolic decompensation. To date, over one thousand different rare IMDs have been identified, which means that healthcare professionals (HCPs) initiating emergency treatment may not be familiar with these conditions. The objective of this initiative was to provide HCPs with practical guidance for the acute management of children and adults with IMDs who need emergency care, regardless of the underlying reason.METHODS: We outline how a multidisciplinary working group from the French IMDs Healthcare Network for Rare Diseases, known as G2M, has created concise and standardized protocols _each consisting of a single double-sided A4 sheet _ focused on a specific disease, a group of diseases, or a particular symptom. Prior to validation, these protocols were reviewed by all French reference and competence centres for IMDs, as well as by medical experts from other specialities when necessary, physicians from emergency and intensive care units, and representatives from patient associations.
RESULTS AND CONCLUSION: In total, 51 emergency protocols containing essential information have been developed and provided to affected patients. All the emergency protocols are freely available in both French and English at https://www.filiere-g2m.fr/urgences. These standardized protocols aim to enhance the emergency care of patients without delay, while also assisting HCPs by increasing their confidence and efficiency, minimizing the risk of dosage errors when administering specialized treatments, saving time, and reducing the number of phone calls to metabolic medicine specialists on night duty. The protocols are scheduled for annual review to facilitate further improvements based on feedback from HCPs and patients, as well as to accommodate any changes in management practices as they evolve.

Keywords: Acute decompensation; Drug contraindication; Emergency protocol; Emergency treatment; Inborn errors of metabolism (IEM); Inherited metabolic disorders (IMD)

DOI: https://doi.org/10.1016/j.ymgme.2024.108579