biostudies-literatureD'Souza PNational Institute of Neurological Disorders and StrokeIntramural NIH HHSNational Institute on Deafness and Other Communication DisordersAustralian GovernmentNational Institute of Mental HealthNational Institutes of HealthNational Human Genome Research Institute101144https://www.ebi.ac.uk/biostudies/studies/S-EPMC11348282biostudies-literatureUnknown26(7)<h4>Purpose</h4>GM1 gangliosidosis (GM1) a lysosomal disorder caused by pathogenic variants in GLB1, is characterized by relentless neurodegeneration. There are no approved treatments.<h4>Methods</h4>Forty-one individuals with type II (late-infantile and juvenile) GM1 participated in a single-site prospective observational study.<h4>Results</h4>Classification of 37 distinct variants using American College of Medical Genetics and Genomics criteria resulted in the upgrade of 6 and the submission of 4 new variants. In contrast to type I infantile disease, children with type II had normal or near normal hearing and did not have cherry-red maculae or hepatosplenomegaly. Some older children with juvenile onset disease developed thickened aortic and/or mitral valves. Serial magnetic resonance images demonstrated progressive brain atrophy, more pronounced in late infantile patients. Magnetic resonance spectroscopy showed worsening elevation of myo-inositol and deficit of N-acetyl aspartate that were strongly correlated with scores on the Vineland Adaptive Behavior Scale, progressing more rapidly in late infantile compared with juvenile onset disease.<h4>Conclusion</h4>Serial phenotyping of type II GM1 patients expands the understanding of disease progression and clarifies common misconceptions about type II patients; these are pivotal steps toward more timely diagnosis and better supportive care. The data amassed through this 10-year effort will serve as a robust comparator for ongoing and future therapeutic trials.Genetics in medicine : official journal of the American College of Medical GeneticsGM1 gangliosidosis type II: Results of a 10-year prospective study.PMC113482821ZICMH002961NCT00029965ZIADC000064ZIA HG200409ZIA DC000064ZIC MH002961Z01 HG000107ZIAHG20040902-HG-0107Acosta MTNicoli ERBuckley AHan STHuang RKing KThurm AJordan CPMojica Algarin YRegier DSTifft CJBrewer CSolomon BFarmer CQuimby RMyles JHuryn LAAdams DBaker EHRothermel CEZein WHartman ALZainab MBowden SBrooks BPJohnston JMD'Souza PCrowell AVezina GfalseGM1 gangliosidosis type II: Results of a 10-year prospective study.<h4>Purpose</h4>GM1 gangliosidosis (GM1) a lysosomal disorder caused by pathogenic variants in GLB1, is characterized by relentless neurodegeneration. There are no approved treatments.<h4>Methods</h4>Forty-one individuals with type II (late-infantile and juvenile) GM1 participated in a single-site prospective observational study.<h4>Results</h4>Classification of 37 distinct variants using American College of Medical Genetics and Genomics criteria resulted in the upgrade of 6 and the submission of 4 new variants. In contrast to type I infantile disease, children with type II had normal or near normal hearing and did not have cherry-red maculae or hepatosplenomegaly. Some older children with juvenile onset disease developed thickened aortic and/or mitral valves. Serial magnetic resonance images demonstrated progressive brain atrophy, more pronounced in late infantile patients. Magnetic resonance spectroscopy showed worsening elevation of myo-inositol and deficit of N-acetyl aspartate that were strongly correlated with scores on the Vineland Adaptive Behavior Scale, progressing more rapidly in late infantile compared with juvenile onset disease.<h4>Conclusion</h4>Serial phenotyping of type II GM1 patients expands the understanding of disease progression and clarifies common misconceptions about type II patients; these are pivotal steps toward more timely diagnosis and better supportive care. The data amassed through this 10-year effort will serve as a robust comparator for ongoing and future therapeutic trials.2024-01-01T00:00:00Z2024 Jul2026-06-03T07:28:17.688Z2026-04-25T03:22:40.518ZS-EPMC113482823864199410.1016/j.gim.2024.101144