TY - JOUR
T1 - ALG8-CDG
T2 - Molecular and phenotypic expansion suggests clinical management guidelines
AU - Albokhari, Daniah
AU - Ng, Bobby G.
AU - Guberinic, Alis
AU - Daniel, Earnest James Paul
AU - Engelhardt, Nicole M.
AU - Barone, Rita
AU - Fiumara, Agata
AU - Garavelli, Livia
AU - Trimarchi, Gabriele
AU - Wolfe, Lynne
AU - Raymond, Kimiyo M.
AU - Morava, Eva
AU - He, Miao
AU - Freeze, Hudson H.
AU - Lam, Christina
AU - Edmondson, Andrew C.
N1 - Funding Information:
We thank the patients and their families for participating in this study. University of Washington Center for Mendelian Genomics (UW-CMG) generated genetic data enabling diagnosis in some individuals in our cohort.
Funding Information:
This work was supported by The Rocket Fund and NIH grants R01DK99551 (Hudson H. Freeze), T32 GM008638 (Andrew C. Edmondson) and U54 NS115198 (Christina Lam, Hudson H. Freeze, Kimiyo M. Raymond, Andrew C. Edmondson, Eva Morava, and Miao He) from the National Institute of Neurological Diseases and Stroke (NINDS) and the National Center for Advancing Translational Sciences (NCATS), and the Rare Disorders Clinical Research Network (RDCRN), at the National Institute of Health.
Publisher Copyright:
© 2022 SSIEM.
PY - 2022/9
Y1 - 2022/9
N2 - Congenital disorders of glycosylation are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid glycan biosynthesis. These disorders mostly manifest with multisystem involvement. Individuals with ALG8-CDG commonly present with hypotonia, protein-losing enteropathy, and hepatic involvement. Here, we describe seven unreported individuals diagnosed with ALG8-CDG based on biochemical and molecular testing and we identify nine novel variants in ALG8, bringing the total to 26 individuals with ALG8-CDG in the medical literature. In addition to the typical multisystem involvement documented in ALG8-CDG, our cohort includes the two oldest patients reported and further expands the phenotype of ALG8-CDG to include stable intellectual disability, autism spectrum disorder and other neuropsychiatric symptoms. We further expand the clinical features in a variety of organ systems including ocular, musculoskeletal, dermatologic, endocrine, and cardiac abnormalities and suggest a comprehensive evaluation and monitoring strategy to improve clinical management.
AB - Congenital disorders of glycosylation are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid glycan biosynthesis. These disorders mostly manifest with multisystem involvement. Individuals with ALG8-CDG commonly present with hypotonia, protein-losing enteropathy, and hepatic involvement. Here, we describe seven unreported individuals diagnosed with ALG8-CDG based on biochemical and molecular testing and we identify nine novel variants in ALG8, bringing the total to 26 individuals with ALG8-CDG in the medical literature. In addition to the typical multisystem involvement documented in ALG8-CDG, our cohort includes the two oldest patients reported and further expands the phenotype of ALG8-CDG to include stable intellectual disability, autism spectrum disorder and other neuropsychiatric symptoms. We further expand the clinical features in a variety of organ systems including ocular, musculoskeletal, dermatologic, endocrine, and cardiac abnormalities and suggest a comprehensive evaluation and monitoring strategy to improve clinical management.
KW - N-glycans
KW - congenital disorders of glycosylation
KW - lipid-linked oligosaccharides
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U2 - 10.1002/jimd.12527
DO - 10.1002/jimd.12527
M3 - Article
C2 - 35716054
AN - SCOPUS:85133080299
SN - 0141-8955
VL - 45
SP - 969
EP - 980
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 5
ER -