GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases
GM2 activator deficiency (AB variant of GM2 gangliosidosis) is an ultra-rare autosomal recessive lysosomal storage disorder caused by pathogenic GM2A mutations. The loss of a functional GM2 activator protein disrupts GM2 ganglioside degradation, leading to progressive neurodegeneration. Although it...
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Elsevier
2025-06-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426925000400 |
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| author | Merve Yoldaş Çelik Burcu Köşeci Ezgi Burgaç Kanay Yararbaş |
| author_facet | Merve Yoldaş Çelik Burcu Köşeci Ezgi Burgaç Kanay Yararbaş |
| author_sort | Merve Yoldaş Çelik |
| collection | DOAJ |
| description | GM2 activator deficiency (AB variant of GM2 gangliosidosis) is an ultra-rare autosomal recessive lysosomal storage disorder caused by pathogenic GM2A mutations. The loss of a functional GM2 activator protein disrupts GM2 ganglioside degradation, leading to progressive neurodegeneration. Although it shares clinical features with Tay-Sachs disease, GM2 activator deficiency remains a genetically and biochemically distinct disorder, with limited genotype-phenotype correlation due to the small number of reported cases.This report presents a 33-month-old male with an infantile-onset phenotype, characterized by nystagmus, axial hypotonia, hyperacusis, and bilateral cherry-red spots. Genetic analysis identified a homozygous likely pathogenic c.262_264del (p.Lys88del) mutation, reinforcing its potential association with early disease onset. His clinical course was marked by progressive neurodegeneration, recurrent pulmonary infections, and severe feeding difficulties requiring gastrostomy placement.In addition, previously published cases were reviewed to provide insights into the phenotypic spectrum, age of onset, and key clinical characteristics of GM2 activator deficiency. Among the 22 reported cases, 77.3 % exhibited an infantile-onset phenotype, while 18.2 % and 4.5 % had juvenile and adult-onset forms, respectively. Notably, cherry-red spots and hyperacusis were present in 94.1 % and 82.4 % of infantile cases but were strikingly absent in later-onset phenotypes.This case report, supplemented by a literature review, offers a comprehensive overview of GM2 activator deficiency and underscores the importance of early molecular diagnosis in suspected cases |
| format | Article |
| id | doaj-art-87b5f93bf8c0460293b20cf1e3754372 |
| institution | DOAJ |
| issn | 2214-4269 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj-art-87b5f93bf8c0460293b20cf1e37543722025-08-20T03:21:38ZengElsevierMolecular Genetics and Metabolism Reports2214-42692025-06-014310122510.1016/j.ymgmr.2025.101225GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published casesMerve Yoldaş Çelik0Burcu Köşeci1Ezgi Burgaç2Kanay Yararbaş3Adana City Training and Research Hospital, Department of Pediatric Metabolism, Adana, Turkey; Corresponding author at: Adana City Training and Research Hospital, Department of Pediatric Metabolism and Nutrition, Adana, Turkey.Adana City Training and Research Hospital, Department of Pediatric Metabolism, Adana, TurkeyAdana City Training and Research Hospital, Department of Pediatric Metabolism, Adana, TurkeyDemiroglu Bilim University Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey; Sapiens Genetics Laboratory, TurkeyGM2 activator deficiency (AB variant of GM2 gangliosidosis) is an ultra-rare autosomal recessive lysosomal storage disorder caused by pathogenic GM2A mutations. The loss of a functional GM2 activator protein disrupts GM2 ganglioside degradation, leading to progressive neurodegeneration. Although it shares clinical features with Tay-Sachs disease, GM2 activator deficiency remains a genetically and biochemically distinct disorder, with limited genotype-phenotype correlation due to the small number of reported cases.This report presents a 33-month-old male with an infantile-onset phenotype, characterized by nystagmus, axial hypotonia, hyperacusis, and bilateral cherry-red spots. Genetic analysis identified a homozygous likely pathogenic c.262_264del (p.Lys88del) mutation, reinforcing its potential association with early disease onset. His clinical course was marked by progressive neurodegeneration, recurrent pulmonary infections, and severe feeding difficulties requiring gastrostomy placement.In addition, previously published cases were reviewed to provide insights into the phenotypic spectrum, age of onset, and key clinical characteristics of GM2 activator deficiency. Among the 22 reported cases, 77.3 % exhibited an infantile-onset phenotype, while 18.2 % and 4.5 % had juvenile and adult-onset forms, respectively. Notably, cherry-red spots and hyperacusis were present in 94.1 % and 82.4 % of infantile cases but were strikingly absent in later-onset phenotypes.This case report, supplemented by a literature review, offers a comprehensive overview of GM2 activator deficiency and underscores the importance of early molecular diagnosis in suspected caseshttp://www.sciencedirect.com/science/article/pii/S2214426925000400AB variant GM2 gangliosidosisCherry-red spotsGM2AGM2 activator deficiency |
| spellingShingle | Merve Yoldaş Çelik Burcu Köşeci Ezgi Burgaç Kanay Yararbaş GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases Molecular Genetics and Metabolism Reports AB variant GM2 gangliosidosis Cherry-red spots GM2A GM2 activator deficiency |
| title | GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases |
| title_full | GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases |
| title_fullStr | GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases |
| title_full_unstemmed | GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases |
| title_short | GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases |
| title_sort | gm2 activator deficiency an ultra rare disorder with a new case and review of 22 published cases |
| topic | AB variant GM2 gangliosidosis Cherry-red spots GM2A GM2 activator deficiency |
| url | http://www.sciencedirect.com/science/article/pii/S2214426925000400 |
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