Is hematopoietic stem cell transplantation a therapeutic option for mucolipidosis type II?,Molecular Genetics and Metabolism Reports

当前位置： X-MOL 学术 › Mol. Genet. Metab. Rep. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Is hematopoietic stem cell transplantation a therapeutic option for mucolipidosis type II?
Molecular Genetics and Metabolism Reports ( IF 1.8 ) Pub Date : 2021-01-14 , DOI: 10.1016/j.ymgmr.2020.100704
Luise Sophie Ammer _{1,

2} , Sandra Pohl _{2,

3} , Sandra Rafaela Breyer _{2,

4,

5} , Charlotte Aries _{1,

2} , Jonas Denecke ₁ , Anna Perez _{1,

2} , Martin Petzoldt ₆ , Johanna Schrum ₇ , Ingo Müller ₇ , Nicole Maria Muschol _{1,

2}

Affiliation

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.

中文翻译：