ALG11-CDG

ALG11-CDG (also known as ALG11-congenital disorder of glycosylation, formerly CDG-Ip) is an extremely rare autosomal recessive metabolic disorder caused by pathogenic variants in the ALG11 gene. This gene encodes the enzyme GDP-Man:Man3GlcNAc2-PP-Dol alpha-1,2-mannosyltransferase, which is essential for the early steps of N-linked glycosylation in the endoplasmic reticulum. Deficiency of this enzyme leads to impaired assembly of lipid-linked oligosaccharides, resulting in underglycosylation of numerous glycoproteins throughout the body. ALG11-CDG primarily affects the neurological system, with patients typically presenting in the neonatal or infantile period with severe intellectual disability, seizures (often refractory epilepsy), hypotonia, and significant developmental delay. Additional features may include microcephaly, feeding difficulties, failure to thrive, facial dysmorphism, strabismus, and brain abnormalities visible on neuroimaging such as cerebral and cerebellar atrophy. Some patients also exhibit hepatic involvement, coagulation abnormalities, and skeletal anomalies. The clinical severity can vary but is generally significant. Diagnosis is typically suspected based on an abnormal transferrin isoelectric focusing pattern (type 1 pattern) and confirmed through molecular genetic testing of the ALG11 gene. There is currently no specific or curative treatment for ALG11-CDG. Management is supportive and symptomatic, focusing on seizure control with antiepileptic medications, nutritional support, physical and occupational therapy, and management of individual organ-specific complications. Given the rarity of the condition, with only a limited number of cases reported in the medical literature, long-term prognosis data remain limited.

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