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Diagnosis of metachromatic leukodystrophy in a patient with regression and Phelan-McDermid syndrome

  • Hyunji Ahn
    Affiliations
    Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea
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  • Go Hun Seo
    Affiliations
    3 Billion, Inc., Seoul, Republic of Korea
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  • Changwon Keum
    Affiliations
    3 Billion, Inc., Seoul, Republic of Korea
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  • Sun Hee Heo
    Affiliations
    ASAN Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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  • Taeho Kim
    Affiliations
    ASAN Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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  • Jeongmin Choi
    Affiliations
    ASAN Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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  • Author Footnotes
    1 These two authors contribute equally on this work.
    Mi-Sun Yum
    Correspondence
    Corresponding authors at: Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.
    Footnotes
    1 These two authors contribute equally on this work.
    Affiliations
    Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 These two authors contribute equally on this work.
    Beom Hee Lee
    Correspondence
    Corresponding authors at: Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.
    Footnotes
    1 These two authors contribute equally on this work.
    Affiliations
    Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea

    ASAN Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 These two authors contribute equally on this work.
Published:February 26, 2020DOI:https://doi.org/10.1016/j.braindev.2020.02.003

      Abstract

      Phelan-McDermid syndrome (PMS) is a 22q13.3 deletion syndrome. Most PMS patients show global developmental delay and some of them suffer from developmental regression. The deleted region contains ARSA, which is responsible for metachromatic leukodystrophy (MLD). Here we report an extremely rare case of PMS characterized by unusual, rapidly progressive developmental regression due to additional pathogenic mutation in ARSA. Considering the 1 in 100 chance of an MLD carrier, co-occurrence of PMS and MLD in a patient is possible if either parent carries a heterozygous ARSA mutation. Therefore, MLD should be ruled out in PMS patients with severe neurological phenotype.

      Keywords

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      References

        • Phelan M.C.
        Deletion 22q13.3 syndrome.
        Orphanet J Rare Dis. 2008; 3: 14
        • Betancur C.
        • Buxbaum J.D.
        SHANK3 haploinsufficiency: a “common” but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders.
        Mol Autism. 2013; 4: 17
        • Bonaglia M.C.
        • Giorda R.
        • Beri S.
        • De Agostini C.
        • Novara F.
        • Fichera M.
        • et al.
        Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome.
        PLoS Genet. 2011; 7e1002173
        • Reierson G.
        • Bernstein J.
        • Froehlich-Santino W.
        • Urban A.
        • Purmann C.
        • Berquist S.
        • et al.
        Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome).
        J Psychiatr Res. 2017; 91: 139-144
        • Dhar S.U.
        • del Gaudio D.
        • German J.R.
        • Peters S.U.
        • Ou Z.
        • Bader P.I.
        • et al.
        22q13.3 deletion syndrome: clinical and molecular analysis using array CGH.
        Am J Med Genet A. 2010; 152a: 573-581
        • van Rappard D.F.
        • Boelens J.J.
        • Wolf N.I.
        Metachromatic leukodystrophy: disease spectrum and approaches for treatment.
        Best Pract Res Clin Endocrinol Metab. 2015; 29: 261-273
      1. Seo GH, Park J-y, Kim S, Lee J, Oh A, lee Y, et al. High diagnostic yield and clinical utility of WES for patients with undiagnosed genetic disorder by automating variant interpretation. BioRxiv 628438 [Preprint]. 2019 [cited 2019 Oct 23]. doi: https://doi.org/10.1101/628438.

        • Richards S.
        • Aziz N.
        • Bale S.
        • Bick D.
        • Das S.
        • Gastier-Foster J.
        • 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: 405-424
        • Sarasua S.M.
        • Dwivedi A.
        • Boccuto L.
        • Rollins J.D.
        • Chen C.F.
        • Rogers R.C.
        • et al.
        Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome).
        J Med Genet. 2011; 48: 761-766
        • Artigalas O.
        • Paskulin G.
        • Riegel M.
        • Burin M.
        • Saraiva-Pereira M.L.
        • Maluf S.
        • et al.
        A patient presenting a 22q13 deletion associated with an apparently balanced translocation t(16;22): An illustrative case in the investigation of patients with low ARSA activity.
        Genet Mol Biol. 2012; 35: 424-427