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First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation

We report the case of a boy who was diagnosed with mucopolysaccharidosis (MPS) VII at two weeks of age. He harbored three missense β-glucuronidase (GUSB) variations in exon 3: two novel, c.422A>C and c.424C>T, inherited from his mother, and the rather common c.526C>T, inherited from his fat...

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Autores principales: Dubot, Patricia, Sabourdy, Frédérique, Plat, Geneviève, Jubert, Charlotte, Cancès, Claude, Broué, Pierre, Touati, Guy, Levade, Thierry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861985/
https://www.ncbi.nlm.nih.gov/pubmed/31661765
http://dx.doi.org/10.3390/ijms20215345
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author Dubot, Patricia
Sabourdy, Frédérique
Plat, Geneviève
Jubert, Charlotte
Cancès, Claude
Broué, Pierre
Touati, Guy
Levade, Thierry
author_facet Dubot, Patricia
Sabourdy, Frédérique
Plat, Geneviève
Jubert, Charlotte
Cancès, Claude
Broué, Pierre
Touati, Guy
Levade, Thierry
author_sort Dubot, Patricia
collection PubMed
description We report the case of a boy who was diagnosed with mucopolysaccharidosis (MPS) VII at two weeks of age. He harbored three missense β-glucuronidase (GUSB) variations in exon 3: two novel, c.422A>C and c.424C>T, inherited from his mother, and the rather common c.526C>T, inherited from his father. Expression of these variations in transfected HEK293T cells demonstrated that the double mutation c.422A>C;424C>T reduces β-glucuronidase enzyme activity. Enzyme replacement therapy (ERT), using UX003 (vestronidase alfa), was started at four months of age, followed by a hematopoietic stem cell allograft transplantation (HSCT) at 13 months of age. ERT was well tolerated and attenuated visceromegaly and skin infiltration. After a severe skin and gut graft-versus-host disease, ERT was stopped six months after HSCT. The last follow-up examination (at the age of four years) revealed a normal psychomotor development, stabilized growth curve, no hepatosplenomegaly, and no other organ involvement. Intriguingly, enzyme activity had normalized in leukocytes but remained low in plasma. This case report illustrates: (i) The need for an early diagnosis of MPS, and (ii) the possible benefit of a very early enzymatic and/or cellular therapy in this rare form of lysosomal storage disease.
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spelling pubmed-68619852019-12-05 First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation Dubot, Patricia Sabourdy, Frédérique Plat, Geneviève Jubert, Charlotte Cancès, Claude Broué, Pierre Touati, Guy Levade, Thierry Int J Mol Sci Case Report We report the case of a boy who was diagnosed with mucopolysaccharidosis (MPS) VII at two weeks of age. He harbored three missense β-glucuronidase (GUSB) variations in exon 3: two novel, c.422A>C and c.424C>T, inherited from his mother, and the rather common c.526C>T, inherited from his father. Expression of these variations in transfected HEK293T cells demonstrated that the double mutation c.422A>C;424C>T reduces β-glucuronidase enzyme activity. Enzyme replacement therapy (ERT), using UX003 (vestronidase alfa), was started at four months of age, followed by a hematopoietic stem cell allograft transplantation (HSCT) at 13 months of age. ERT was well tolerated and attenuated visceromegaly and skin infiltration. After a severe skin and gut graft-versus-host disease, ERT was stopped six months after HSCT. The last follow-up examination (at the age of four years) revealed a normal psychomotor development, stabilized growth curve, no hepatosplenomegaly, and no other organ involvement. Intriguingly, enzyme activity had normalized in leukocytes but remained low in plasma. This case report illustrates: (i) The need for an early diagnosis of MPS, and (ii) the possible benefit of a very early enzymatic and/or cellular therapy in this rare form of lysosomal storage disease. MDPI 2019-10-28 /pmc/articles/PMC6861985/ /pubmed/31661765 http://dx.doi.org/10.3390/ijms20215345 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Dubot, Patricia
Sabourdy, Frédérique
Plat, Geneviève
Jubert, Charlotte
Cancès, Claude
Broué, Pierre
Touati, Guy
Levade, Thierry
First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation
title First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation
title_full First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation
title_fullStr First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation
title_full_unstemmed First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation
title_short First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation
title_sort first report of a patient with mps type vii, due to novel mutations in gusb, who underwent enzyme replacement and then hematopoietic stem cell transplantation
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861985/
https://www.ncbi.nlm.nih.gov/pubmed/31661765
http://dx.doi.org/10.3390/ijms20215345
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