Progressive loss of cerebral structures in ALG11-related congenital disorder of glycosylation

Authors

Olivier Fortin, Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia.
Gilbert Vezina, Department of Radiology, Children's National Hospital, Washington, District of Columbia; Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
David M. Steinhorn, Hinds Hospice Children's Program, University of California San Francisco-Fresno School of Medicine, Fresno, California.
Sarah B. Mulkey, Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia; Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia. Electronic address: sbmulkey@childrensnational.org.

Document Type

Journal Article

Publication Date

3-1-2025

Journal

Pediatric neurology

Volume

164

DOI

10.1016/j.pediatrneurol.2024.12.009

Keywords

Brain atrophy; Congenital disorders of glycosylation; Fetal neurology; Neurogenetics; Neuroimaging; Palliative care

Abstract

BACKGROUND: Congenital disorders of glycosylation (CDG) are a group of metabolic disorders related to dysfunctional glycoprotein and glycolipid biosynthesis. ALG11-related CDG is a rare member of this group, characterized by severe neurodevelopmental impairment, progressive microcephaly, sensorineural hearing loss, and epilepsy. The objective of this report is to provide an update on the phenotype and brain magnetic resonance imaging (MRI) at age seven years for a patient initially described in early infancy with fetal brain disruption sequence. METHODS: We provide an updated detailed clinical description of a seven-year-old male with ALG-11 CDG who underwent brain MRI at age seven years. RESULTS: Brain MRI at age seven years showed significant disease progression compared to the neonatal brain MRI. There was near complete loss of cerebral hemispheres, severe cerebellar atrophy, and decreased volume of the brainstem. The prior brain MRI (done at six weeks of age) had shown severe supratentorial volume loss but a relatively preserved cerebellum and brainstem at that time. CONCLUSIONS: Reports on the natural history of rare conditions are important to improve our understanding of these conditions. ALG11-CDG is associated with atrophy and eventual vanishing of supratentorial brain structures, and infratentorial brain structures later in the disease process. The involvement of a pediatric palliative care service is a valuable adjunct to assist with symptom management and family support for these complex progressive conditions.

APA Citation

Fortin, Olivier; Vezina, Gilbert; Steinhorn, David M.; and Mulkey, Sarah B., "Progressive loss of cerebral structures in ALG11-related congenital disorder of glycosylation" (2025). GW Authored Works. Paper 6922.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6922

Department

Radiology