Single Institutional Experience with GM1 Gangliosidosis: Clinical and Laboratory Results of 14 Patients

Akar, Halil Tuna; Yıldız, Yılmaz; Güvenkaya, Gökhan; Çıkı, Kısmet; Kahraman, Ayşe Burcu; Erdal, İzzet; Coşkun, Turgay; Dursun, Ali; Sivri, Hatice Serap; Tokatlı, Ayşegül

doi:10.4274/balkanmedj.galenos.2022.2022-3-75

Cited by 2 publications

(1 citation statement)

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“…8–10 Infantile patients with multi-organ dysfunction, including hepatosplenomegaly, cardiomyopathy, skeletal dysplasia, coarse facial features, cherry red maculae and extensive Mongolian spots 11–16 , typically have a life expectancy of 2–3 years. 17,18 Like other lysosomal storage diseases, type I GM1 can also present as nonimmune hydrops fetalis. 10,19 Type II (MIM #230600) is less severe and has later onset than type I, and based on the timing of observable symptom onset can be further classified into late infantile (around 1 year of age) and juvenile onset (3 – 5 years).…”

Section: Introductionmentioning

confidence: 99%

GM1 Gangliosidosis Type II: Results of a 10-Year Prospective Study

D’Souza,

Farmer,

Johnston

et al. 2024

Preprint

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PurposeGM1 gangliosidosis (GM1) is an ultra-rare lysosomal storage disease caused by pathogenic variants in galactosidase beta 1 (GLB1; NM_000404), primarily characterized by neurodegeneration, often in children. There are no approved treatments for GM1, but clinical trials using gene therapy (NCT03952637,NCT04713475) and small molecule substrate inhibitors (NCT04221451) are ongoing. Understanding the natural history of GM1 is essential for timely diagnosis, facilitating better supportive care, and contextualizing the results of therapeutic trials.MethodsForty-one individuals with type II GM1 (n=17 late infantile and n=24 juvenile onset) participated in a single-site prospective observational study. Here, we describe the results of extensive multisystem assessment batteries, including clinical labs, neuroimaging, physiological exams, and behavioral assessments.ResultsClassification of 37 distinct variants in this cohort was performed according to ACMG criteria and resulted in the upgrade of six and the submission of four new variants to pathogenic or likely pathogenic. In contrast to type I infantile, children with type II disease exhibited normal or near normal hearing and did not have cherry red maculae or significant hepatosplenomegaly. Some older children with juvenile onset developed thickened aortic and/or mitral valves with regurgitation. Serial MRIs demonstrated progressive brain atrophy that were more pronounced in those with late infantile onset. MR spectroscopy showed worsening elevation of myo-inositol and deficit ofN-acetyl aspartate that were strongly correlated with scores on the Vineland Adaptive Behavior Scale and progress more rapidly in late infantile than juvenile onset disease.ConclusionThe comprehensive serial phenotyping of type II GM1 patients expands the understanding of disease progression and clarifies some common misconceptions about type II patients. Findings from this 10-year endeavor are a pivotal step toward more timely diagnosis and better supportive care for patients. The wealth of data amassed through this effort will serve as a robust comparator for ongoing and future therapeutic trials.

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