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Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort

Multiple sulfatase deficiency (MSD) is a lysosomal storage disease caused by a deficiency of formylglycine‐generating enzyme due to SUMF1 defects. MSD may be misdiagnosed as metachromatic leukodystrophy (MLD), as neurological and neuroimaging findings are similar, and arylsulfatase A (ARSA) deficien...

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Autores principales: Beck‐Wödl, Stefanie, Kehrer, Christiane, Harzer, Klaus, Haack, Tobias B., Bürger, Friederike, Haas, Dorothea, Rieß, Angelika, Groeschel, Samuel, Krägeloh‐Mann, Ingeborg, Böhringer, Judith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932862/
https://www.ncbi.nlm.nih.gov/pubmed/33728250
http://dx.doi.org/10.1002/jmd2.12189
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author Beck‐Wödl, Stefanie
Kehrer, Christiane
Harzer, Klaus
Haack, Tobias B.
Bürger, Friederike
Haas, Dorothea
Rieß, Angelika
Groeschel, Samuel
Krägeloh‐Mann, Ingeborg
Böhringer, Judith
author_facet Beck‐Wödl, Stefanie
Kehrer, Christiane
Harzer, Klaus
Haack, Tobias B.
Bürger, Friederike
Haas, Dorothea
Rieß, Angelika
Groeschel, Samuel
Krägeloh‐Mann, Ingeborg
Böhringer, Judith
author_sort Beck‐Wödl, Stefanie
collection PubMed
description Multiple sulfatase deficiency (MSD) is a lysosomal storage disease caused by a deficiency of formylglycine‐generating enzyme due to SUMF1 defects. MSD may be misdiagnosed as metachromatic leukodystrophy (MLD), as neurological and neuroimaging findings are similar, and arylsulfatase A (ARSA) deficiency and enhanced urinary sulfatide excretion may also occur. While ARSA deficiency seems a cause for neurological symptoms and later neurodegenerative disease course, deficiency of other sulfatases results in clinical features such as dysmorphism, dysostosis, or ichthyosis. We report on a girl and a boy of the same origin presenting with severe ARSA deficiency and neurological and neuroimaging features compatible with MLD. However, exome sequencing revealed not yet described homozygosity of the missense variant c.529G > C, p.Ala177Pro in SUMF1. We asked whether dynamics of disease course differs between MSD and MLD. Comparison to a cohort of 59 MLD patients revealed different disease course concerning onset and disease progression in both MSD patients. The MSD patients showed first gross motor symptoms earlier than most patients with juvenile MLD (<10th percentile of Gross‐Motor‐Function in MLD [GMFC‐MLD] 1). However, subsequent motor decline was more protracted (75th and 90th percentile of GMFC‐MLD 2 (loss of independent walking) and 75th percentile of GMFC‐MLD 5 (loss of any locomotion)). Language decline started clearly after 50th percentile of juvenile MLD and progressed rapidly. Thus, dynamics of disease course may be a further clue for the characterization of MSD. These data may contribute to knowledge of natural course of ultra‐rare MSD and be relevant for counseling and therapy.
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spelling pubmed-79328622021-03-15 Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort Beck‐Wödl, Stefanie Kehrer, Christiane Harzer, Klaus Haack, Tobias B. Bürger, Friederike Haas, Dorothea Rieß, Angelika Groeschel, Samuel Krägeloh‐Mann, Ingeborg Böhringer, Judith JIMD Rep Research Reports Multiple sulfatase deficiency (MSD) is a lysosomal storage disease caused by a deficiency of formylglycine‐generating enzyme due to SUMF1 defects. MSD may be misdiagnosed as metachromatic leukodystrophy (MLD), as neurological and neuroimaging findings are similar, and arylsulfatase A (ARSA) deficiency and enhanced urinary sulfatide excretion may also occur. While ARSA deficiency seems a cause for neurological symptoms and later neurodegenerative disease course, deficiency of other sulfatases results in clinical features such as dysmorphism, dysostosis, or ichthyosis. We report on a girl and a boy of the same origin presenting with severe ARSA deficiency and neurological and neuroimaging features compatible with MLD. However, exome sequencing revealed not yet described homozygosity of the missense variant c.529G > C, p.Ala177Pro in SUMF1. We asked whether dynamics of disease course differs between MSD and MLD. Comparison to a cohort of 59 MLD patients revealed different disease course concerning onset and disease progression in both MSD patients. The MSD patients showed first gross motor symptoms earlier than most patients with juvenile MLD (<10th percentile of Gross‐Motor‐Function in MLD [GMFC‐MLD] 1). However, subsequent motor decline was more protracted (75th and 90th percentile of GMFC‐MLD 2 (loss of independent walking) and 75th percentile of GMFC‐MLD 5 (loss of any locomotion)). Language decline started clearly after 50th percentile of juvenile MLD and progressed rapidly. Thus, dynamics of disease course may be a further clue for the characterization of MSD. These data may contribute to knowledge of natural course of ultra‐rare MSD and be relevant for counseling and therapy. John Wiley & Sons, Inc. 2020-12-08 /pmc/articles/PMC7932862/ /pubmed/33728250 http://dx.doi.org/10.1002/jmd2.12189 Text en © 2020 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Reports
Beck‐Wödl, Stefanie
Kehrer, Christiane
Harzer, Klaus
Haack, Tobias B.
Bürger, Friederike
Haas, Dorothea
Rieß, Angelika
Groeschel, Samuel
Krägeloh‐Mann, Ingeborg
Böhringer, Judith
Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort
title Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort
title_full Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort
title_fullStr Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort
title_full_unstemmed Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort
title_short Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort
title_sort long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort
topic Research Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932862/
https://www.ncbi.nlm.nih.gov/pubmed/33728250
http://dx.doi.org/10.1002/jmd2.12189
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