Is hematopoietic stem cell transplantation a therapeutic option for mucolipidosis type II?

Molecular Genetics and Metabolism Reports

Sandra Rafaela Breyer¹  Johanna Schrum²  Jonas Denecke³  Martin Petzoldt⁴  Sandra Pohl⁵  Nicole Maria Muschol⁵  Luise Sophie Ammer⁶  Ingo Müller⁶  Anna Perez⁷  Charlotte Aries⁷ 

[1] Corresponding author at: Department of Pediatrics, International Center for Lysosomal Disorders (ICLD), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.;Department of Orthopedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Pediatric Orthopedics, Children's Hospital Altona, Hamburg, Germany;International Center for Lysosomal Disorders (ICLD), University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;International Center for Lysosomal Disorders (ICLD), University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

关键词: Mucolipidosis type II;    I-cell disease;    Lysosomal storage disorder;    Hematopoietic stem cell transplantation;    Bone marrow cell transplantation;    Treatment;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Mucolipidosis type II (MLII) is an ultra-rare lysosomal storage disorder caused by defective lysosomal enzyme trafficking. Clinical hallmarks are craniofacial dysmorphia, cardiorespiratory dysfunction, hepatosplenomegaly, skeletal deformities and neurocognitive retardation. Death usually occurs in the first decade of life and no cure exists. Hematopoietic stem cell transplantation (HSCT) has been performed in few MLII patients, but comprehensive follow-up data are extremely scarce. Methods: MLII diagnosis was confirmed in a female three-month-old patient with the mutations c.2213C > A and c.2220_2221dup in the GNPTAB gene. At nine months of age, the patient received HSCT from a 9/10 human leukocyte antigen (HLA)-matched unrelated donor. Results: HSCT resulted in a sustained reduction of lysosomal storage und bone metabolism markers. At six years of age, the patient showed normal cardiac function, partial respiratory insufficiency and moderate hepatomegaly, whereas skeletal manifestations had progressed. However, the patient could walk and maintained an overall good quality of life. Neurocognitive testing revealed a developmental quotient of 36%. The patient died at 6.6 years of age following a human metapneumovirus (hMPV) pneumonia. Conclusions: The exact benefit remains unclear as current literature vastly lacks comparable data on MLII natural history patients. In order to evaluate experimental therapies, in-depth prospective studies and registries of untreated MLII patients are indispensable.

【 授权许可】

Unknown