Advertisement

Quantitative longitudinal natural history of 8 gangliosidoses—conceptual framework and baseline data of the German 8-in-1 disease registry. A cross-sectional analysis

Published:October 03, 2022DOI:https://doi.org/10.1016/j.gim.2022.09.001

      ABSTRACT

      Purpose

      Gangliosidoses are a group of inherited neurogenetic autosomal recessive lysosomal storage disorders usually presenting with progressive macrocephaly, developmental delay, and regression, leading to significant morbidity and premature death. A quantitative definition of the natural history would support and enable clinical development of specific therapies.

      Methods

      Single disease registry of 8 gangliosidoses (NCT04624789). Cross-sectional analysis of baseline data in N = 26 patients. Primary end point: disease severity assessed by the 8-in-1 score. Secondary end points: first neurologic sign or symptom observed (1) by parents and (2) by physicians, diagnostic delay, as well as phenotypical characterization. Tertiary end points: neurologic outcomes (development, ataxia, dexterity) and disability.

      Results

      The 8-in-1 score quantitatively captured severity of disease. Parents recognized initial manifestations (startle reactions) earlier than physicians (motor developmental delay and hypotonia). Median diagnostic delay was 3.16 (interquartile range 0.69-6.25) years. In total, 8 patients presented with late-infantile phenotypes.

      Conclusion

      Data in this registry raise awareness of these rare and fatal conditions to accelerate diagnosis, inform counseling of afflicted families, define quantitative end points for clinical trials, and can serve as historical controls for future therapeutic studies. We provide further insight into the rare late-infantile phenotype for GM2-gangliosidosis. Longitudinal follow up is planned.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      ACMG Member Login

      Are you an ACMG Member? Sign in for online access.

      Subscribe:

      Subscribe to Genetics in Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Suzuki Y.
        • Nanba E.
        • Matsuda J.
        • Higaki K.
        • Oshima A.
        β-galactosidase deficiency (β-galactosidosis): GM1 gangliosidosis and Morquio B disease.
        in: Valle D.L. Antonarakis S. Ballabio A. Beaudet A.L. Mitchell G.A. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, 2019
        • Sandhoff K.
        • Harzer K.
        Gangliosides and gangliosidoses: principles of molecular and metabolic pathogenesis.
        J Neurosci. 2013; 33: 10195-10208https://doi.org/10.1523/JNEUROSCI.0822-13.2013
        • Gravel R.A.
        • Kaback M.M.
        • Proia R.L.
        • Sandhoff K.
        • Suzuki K.
        • Suzuki K.
        The GM2 gangliosidoses.
        in: Valle D.L. Antonarakis S. Ballabio A. Beaudet A.L. Mitchell G.A. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, 2019
        • d’Azzo A.
        • Andria G.
        • Bonten E.
        • Annunziata I.
        Galactosialidosis.
        in: Valle D.L. Antonarakis S. Ballabio A. Beaudet A.L. Mitchell G.A. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, 2019
        • Toro C.
        • Zainab M.
        • Tifft C.J.
        The GM2 gangliosidoses: unlocking the mysteries of pathogenesis and treatment.
        Neurosci Lett. 2021; 764136195https://doi.org/10.1016/j.neulet.2021.136195
      1. Orphanet. Orphanet report series. Prevalence and incidence of rare diseases: bibliographic data. Number 1. Orphanet. Published January 2021. Accessed October 13, 2021. https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf

        • Sláma T.
        • Garbade S.F.
        • Kölker S.
        • Hoffmann G.F.
        • Ries M.
        Quantitative natural history characterization in a cohort of 142 published cases of patients with galactosialidosis-a cross-sectional study.
        J Inherit Metab Dis. 2019; 42: 295-302https://doi.org/10.1002/jimd.12010
        • Garbade S.F.
        • Zielonka M.
        • Komatsuzaki S.
        • et al.
        Quantitative retrospective natural history modeling for orphan drug development.
        J Inherit Metab Dis. 2021; 44: 99-109https://doi.org/10.1002/jimd.12304
        • Austin C.P.
        • Cutillo C.M.
        • Lau L.P.L.
        • et al.
        Future of rare diseases research 2017-2027: an IRDiRC perspective.
        Clin Transl Sci. 2018; 11: 21-27https://doi.org/10.1111/cts.12500
        • Hollak C.E.M.
        • Sirrs S.
        • van den Berg S.
        • et al.
        Registries for orphan drugs: generating evidence or marketing tools?.
        Orphanet J Rare Dis. 2020; 15: 235https://doi.org/10.1186/s13023-020-01519-0
        • Vandenbroucke J.P.
        • von Elm E.
        • Altman D.G.
        • et al.
        Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.
        PLoS Med. 2007; 4: e297https://doi.org/10.1371/journal.pmed.0040297
        • Iturriaga C.
        • Pineda M.
        • Fernández-Valero E.M.
        • Vanier M.T.
        • Coll M.J.
        Niemann-Pick C disease in Spain: clinical spectrum and development of a disability scale.
        J Neurol Sci. 2006; 249: 1-6https://doi.org/10.1016/j.jns.2006.05.054
        • Steinfeld R.
        • Heim P.
        • von Gregory H.
        • et al.
        Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations.
        Am J Med Genet. 2002; 112: 347-354https://doi.org/10.1002/ajmg.10660
      2. Regier DS, Tifft CJ, Rothermel CE. GLB1-related disorders. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1993-2022. Published October 17, 2013. Updated April 22, 2021. Accessed April 7, 2022. https://www.ncbi.nlm.nih.gov/pubmed/24156116

      3. Toro C, Shirvan L, Tifft C. HEXA disorders. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1993-2022. Published March 11, 1999. Updated October 1, 2020. Accessed April 7, 2022. https://www.ncbi.nlm.nih.gov/pubmed/20301397

        • Darrah J.
        • Piper M.
        • Watt M.J.
        Assessment of gross motor skills of at-risk infants: predictive validity of the Alberta Infant Motor Scale.
        Dev Med Child Neurol. 1998; 40: 485-491https://doi.org/10.1111/j.1469-8749.1998.tb15399.x
        • Sparrow S.S.
        • Cicchetti D.V.
        Diagnostic uses of the Vineland Adaptive Behavior Scales.
        J Pediatr Psychol. 1985; 10: 215-225https://doi.org/10.1093/jpepsy/10.2.215
        • Schmitz-Hübsch T.
        • du Montcel S.T.
        • Baliko L.
        • et al.
        Scale for the assessment and rating of ataxia: development of a new clinical scale.
        Neurology. 2006; 66 (Published correction appears in Neurology. 2006;67(2):299.): 1717-1720
        • Subramony S.H.
        SARA—a new clinical scale for the assessment and rating of ataxia.
        Nat Clin Pract Neurol. 2007; 3: 136-137https://doi.org/10.1038/ncpneuro0426
        • Bremova T.
        • Malinová V.
        • Amraoui Y.
        • et al.
        Acetyl-dl-leucine in Niemann-Pick type C: a case series.
        Neurology. 2015; 85: 1368-1375https://doi.org/10.1212/WNL.0000000000002041
        • Kellor M.
        • Frost J.
        • Silberberg N.
        • Iversen I.
        • Cummings R.
        Hand strength and dexterity.
        Am J Occup Ther. 1971; 25: 77-83
        • Mathiowetz V.
        • Weber K.
        • Kashman N.
        • Volland G.
        Adult norms for the Nine Hole Peg Test of finger dexterity.
        Occup Ther J Res. 1985; 5: 24-38https://doi.org/10.1177/153944928500500102
        • Poole J.L.
        • Burtner P.A.
        • Torres T.A.
        • et al.
        Measuring dexterity in children using the Nine-Hole Peg Test.
        J Hand Ther. 2005; 18: 348-351https://doi.org/10.1197/j.jht.2005.04.003
      4. Üstün TB, Kostanjsek N, Chatterji S, Rehm J, eds. Measuring health and disability: manual for WHO Disability Assessment Schedule (WHODAS 2.0). Published 2010. Accessed October 13, 2021. http://www.who.int/standards/classifications/international-classification-of-functioning-disability-and-health/who-disability-assessment-schedule

        • Federici S.
        • Bracalenti M.
        • Meloni F.
        • Luciano J.V.
        World Health Organization disability assessment schedule 2.0: an international systematic review.
        Disabil Rehabil. 2017; 39: 2347-2380https://doi.org/10.1080/09638288.2016.1223177
        • Richards S.
        • Aziz N.
        • Bale S.
        • et al.
        Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
        Genet Med. 2015; 17: 405-424https://doi.org/10.1038/gim.2015.30
        • Slavkovic S.
        • Golubovic S.
        • Vojnovic M.
        • Nadj C.
        Influence of cognitive and motor abilities on the level of current functioning in people with multiple sclerosis.
        Zdr Varst. 2019; 58: 54-61https://doi.org/10.2478/sjph-2019-0007
        • Nestrasil I.
        • Ahmed A.
        • Utz J.M.
        • Rudser K.
        • Whitley C.B.
        • Jarnes-Utz J.R.
        Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: volumetric quantitative MRI study.
        Mol Genet Metab. 2018; 123: 97-104https://doi.org/10.1016/j.ymgme.2017.12.432
        • Jarnes Utz J.R.
        • Kim S.
        • King K.
        • et al.
        Infantile gangliosidoses: mapping a timeline of clinical changes.
        Mol Genet Metab. 2017; 121: 170-179https://doi.org/10.1016/j.ymgme.2017.04.011
        • Bley A.E.
        • Giannikopoulos O.A.
        • Hayden D.
        • Kubilus K.
        • Tifft C.J.
        • Eichler F.S.
        Natural history of infantile G(M2) gangliosidosis.
        Pediatrics. 2011; 128: e1233-e1241https://doi.org/10.1542/peds.2011-0078
        • Maegawa G.H.
        • Stockley T.
        • Tropak M.
        • et al.
        The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported.
        Pediatrics. 2006; 118: e1550-e1562https://doi.org/10.1542/peds.2006-0588
        • Zielonka M.
        • Garbade S.F.
        • Kölker S.
        • Hoffmann G.F.
        • Ries M.
        A cross-sectional quantitative analysis of the natural history of Farber disease: an ultra-orphan condition with rheumatologic and neurological cardinal disease features.
        Genet Med. 2018; 20: 524-530https://doi.org/10.1038/gim.2017.133