PDF herunterladen
Neuropediatrics 2019; 50(04): 248-252
DOI: 10.1055/s-0039-1684052
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

A Novel Homozygous Mutation in the FUCA1 Gene Highlighting Fucosidosis as a Cause of Dystonia: Case Report and Literature Review

Gautam Wali
1   Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, St. Leonards, Australia
,
G. M. Wali
2   Neurospecialities Centre, Belgaum, India
,
Carolyn M. Sue
1   Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, St. Leonards, Australia
,
Kishore R. Kumar 
1   Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, St. Leonards, Australia
3   Translational Genome Informatics Team, Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Australia
› Institutsangaben Funding Dr G.W. is funded by the Spastic Paraplegia Foundation Incorporated. Author C.M.S. is a MRFF NHMRC Practitioner Fellow (APP1136800) and is supported by grants from NHMRC (1103757, 1141064, 1151906), the NSW Genomics Collaborative Grants scheme, Parkinson's NSW, Brain Foundation, and the Australian Mitochondrial Disease Foundation. Author C.M.S. has accepted honoraria for participating in advisory boards of Abbvie, Stada and Stealth BioTherapeutics Inc. Dr K.R.K. receives philanthropic research funding from the Paul Ainsworth Family Foundation.
Weitere Informationen

Publikationsverlauf

05. November 2018

09. Februar 2019

Publikationsdatum:
07. Mai 2019 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Background Fucosidosis is a rare lysosomal disorder caused by mutations in the FUCA1 gene. We describe here a novel homozygous mutation in FUCA1 in an Indian fucosidosis case. Furthermore, we summarize the clinical and genetic findings in the most recently reported individuals with fucosidosis.

Case The proband is an 8-year-old boy born to consanguineous parents. He had generalized dystonia and bilateral spasticity as well as coarse facies, dysostosis multiplex, recurrent infections, angiokeratoma corporis diffusum, and visceromegaly. Whole exome sequencing analysis detected a homozygous canonical splice variant in the FUCA1 gene [Chr1(GRCh37):g.24172346C > T; NM_000147.4:c.1261–1G > A], not previously reported as causative of a human phenotype. Low levels of α-fucosidase in patient leukocytes and a positive qualitative urine based thin layer chromatography test for fucosidosis confirmed the diagnosis. Our literature review identified 89 cases of fucosidosis since the last major review. We show that dystonia is a rare manifestation (12%) and that only a small minority of cases receive treatment with transplantation (3.37%).

Conclusion We report a novel homozygous mutation in FUCA1 as the cause of severe neurological phenotype including generalized dystonia. Early recognition of fucosidosis may be important for consideration of promising treatment options, such as bone marrow transplantation.

Keywords

FUCA1 - fucodosis - dystonia - spasticity - whole exome sequencing - case report

* Dr Gautam Wali and Dr G. M. Wali should be considered joint first author


Supplementary Material

 

  • References

  • 1 Provenzale JM, Barboriak DP, Sims K. Neuroradiologic findings in fucosidosis, a rare lysosomal storage disease. AJNR Am J Neuroradiol 1995; 16 (4, Suppl) 809-813
    PubMedSuche in Google Scholar
  • 2 Willems PJ, Seo H-C, Coucke P, Tonlorenzi R, O'Brien JS. Spectrum of mutations in fucosidosis. Eur J Hum Genet 1999; 7 (01) 60-67
    PubMedSuche in Google Scholar
  • 3 Jiang M, Liu S, Jiang H. , et al. Brain abnormalities in fucosidosis: transplantation or supportive therapy?. Metab Brain Dis 2017; 32 (02) 317-320
    CrossrefPubMedSuche in Google Scholar
  • 4 Willems PJ, Gatti R, Darby JK. , et al. Fucosidosis revisited: a review of 77 patients. Am J Med Genet 1991; 38 (01) 111-131
    CrossrefPubMedSuche in Google Scholar
  • 5 Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 2019; 47 (D1): D886-D894
    CrossrefPubMedSuche in Google Scholar
  • 6 Richards S, Aziz N, Bale S. , et al; ACMG Laboratory Quality Assurance Committee. 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 (05) 405-424
    CrossrefPubMedSuche in Google Scholar
  • 7 Arif B, Kumar KR, Seibler P. , et al. A novel OPA3 mutation revealed by exome sequencing: an example of reverse phenotyping. JAMA Neurol 2013; 70 (06) 783-787
    CrossrefPubMedSuche in Google Scholar
  • 8 Jain P, Ramesh K, Mohamed A, Kumar A, Gulati S. Teaching NeuroImages: Distinct neuroimaging features of fucosidosis. Neurology 2012; 78 (05) e33
    CrossrefPubMedSuche in Google Scholar
  • 9 Miano M, Lanino E, Gatti R. , et al. Four year follow-up of a case of fucosidosis treated with unrelated donor bone marrow transplantation. Bone Marrow Transplant 2001; 27 (07) 747-751
    CrossrefPubMedSuche in Google Scholar
  • 10 Vellodi A, Cragg H, Winchester B. , et al. Allogeneic bone marrow transplantation for fucosidosis. Bone Marrow Transplant 1995; 15 (01) 153-158
    PubMedSuche in Google Scholar