bims-meglyc 2026-04-26 papers

Issue of 2026–04–26
two papers selected by
Silvia Radenkovic, UMC Utrecht

Mol Genet Metab. 2026 Apr 20. pii: S1096-7192(26)00418-X. [Epub ahead of print]148(2): 110135

Disease-specific growth charts capture characteristic growth patterns in children with PMM2 - CDG.

Kyriakie Sarafoglou, Christina Lam, Andrew C Edmondson, Andrea Miller, Rodrigo T Starosta, Aziza Zeighami, Seishu Horikoshi, Hayden Vreugdenhil, Fernando Scaglia, Tamas Kozicz, Queenie K G Tan, Bradley S Miller, Iván Martínez-Duncker, Gerard T Berry, Peter McWilliams, Eva Morava, Yaw Addo.

BACKGROUND: Growth faltering is prevalent in 96% of children with Phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG). Published long-term growth data is extremely limited. Growth and weight patterns of PMM2-CDG children differ from the general population limiting the utility of existing normative growth charts to track development trajectory in comparison to peers with PMM2-CDG.
OBJECTIVE: Create PMM2-CDG disease-specific height-, weight-, and BMI-for-age reference growth charts (0-20 years).
METHODS: De-identified growth data was provided by Frontiers in Congenital Disorders of Glycosylation Consortium, CDG Care, Minnesota Partnership for Biotechnology and Medical Genomics, and Glycomine, Inc. Semi-parametric modeling techniques were used to develop PMM2-CDG-specific charts along with nodal-point analyses for quantifying and examining PMM2-CDG growth differences relative to Centers for Disease Control (CDC) reference using one-sided quantile tests.
RESULTS: Data of 156 children (females n = 75) with PMM2-CDG from 1614 visits were used to create height-, weight- and BMI-for-age growth curves. Median follow-up was 8.5 years (SD 4.5) for females and 6.8 years (SD 4.4) for males. CDG females were 13 cm shorter than their CDC reference peers at 20 years (150 vs 163 cm), and males were 16 cm shorter (160 vs 176 cm). All weight and height nodal points were significantly different (p < 0.05) at each age (4, 8, 12, 16, 20 years).
CONCLUSION: PMM2-CDG specific reference charts can help enable the detection of deviations from peer growth patterns, aid in early detection of coexisting endocrinopathies, help guide treatment decisions and evaluate the effectiveness of new disease-modifying treatments in clinical trials.

Keywords: Adiposity rebound; Body mass index (BMI); Congenital disorder of glycosylation (CDG); Genetic disorder; Growth; Metabolic disease; N-linked glycosylation; Phosphomannomutase 2 (PMM2); Puberty

DOI: https://doi.org/10.1016/j.ymgme.2026.110135

Seizure. 2026 Apr 01. pii: S1059-1311(26)00083-X. [Epub ahead of print]138 93-102

Genotype and phenotype spectrum of epilepsy patients with congenital disorders of glycosylation associated with GPAA1 variants.

Shijia Ouyang, Ting Wang, Xiaojuan Tian, Zeyong Dong, Quanzhen Tan, Ying Yang, Xiaoling Yang, Yuehua Zhang.

OBJECTIVE: To delineate the genotype and phenotype of epilepsy patients with GPAA1-related congenital disorders of glycosylation (CDG).
METHODS: Whole-exome sequencing was performed to all epilepsy patients suspected with genetic etiology from June 2017 to October 2025. Clinical data of five patients with GPAA1 variants from our study and 19 patients from published studies were collected and analyzed.
RESULTS: This study collected five epilepsy patients with biallelic GPAA1 variants. Eight different GPAA1 variants were identified. All patients exhibited global developmental delay and hypotonia. Seizure occurred at 3-12 months of age. All five patients had myoclonic seizures, four patients had 2 or more seizure types. Cranial MRI revealed cerebellar atrophy in one patient. All patients had drug-resistant epilepsy. When combining data from this study and published studies, 28 variants were identified, including 19 missense variants, 5 frameshift variants, 3 intronic splicing variants, and one nonsense variant. The clinical manifestations included global developmental delay (100%), hypotonia (95.8%), and epilepsy (83.3%). 60% of patients experienced seizure onset before the age of one. The main seizure types were generalized tonic-clonic seizures (GTCS) (82.4%) and myoclonic seizures (70.6%). Febrile sensitivity was presented in 66.7% of patients. 60.9% of patients had cerebellar atrophy.
CONCLUSIONS: The phenotypes of patients with GPAA1 variants included global developmental delay, hypotonia, and epilepsy. The main seizure types were GTCS and myoclonic seizures, and two-thirds of patients' seizures were characterized by febrile sensitivity. Cerebellar atrophy occurred in 60.9% of patients.

Keywords: Congenital disorders of glycosylation; Epilepsy; GPAA1

DOI: https://doi.org/10.1016/j.seizure.2026.03.018