scholarly journals 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

2019 ◽  
Vol 20 (21) ◽  
pp. 5345 ◽  
Author(s):  
Patricia Dubot ◽  
Frédérique Sabourdy ◽  
Geneviève Plat ◽  
Charlotte Jubert ◽  
Claude Cancès ◽  
...  

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.

Author(s):  
Mahmoud Aljurf ◽  
John A. Snowden ◽  
Patrick Hayden ◽  
Kim H. Orchard ◽  
Eoin McGrath

John A. Snowden: From “Department of Haematology, University of Sheffield, Sheffield, UK”


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7033-7033
Author(s):  
Muhammad Umair Mushtaq ◽  
Mary Luder ◽  
Moazzam Shahzad ◽  
Nausheen Ahmed ◽  
Haitham Abdelhakim ◽  
...  

7033 Background: The Coronavirus Disease 2019 (COVID-19) has caused over 25 million infections in the US with over 0.4 million deaths. Hematogenic stem cell transplant (HCT) or cellular therapy (CT) recipients have a high risk of mortality with COVID-19 due to profound immune dysregulation. We aimed to assess the outcomes with COVID-19 in HCT/CT recipients. Methods: A single-center prospective study was conducted, including all (n=40) adult HCT/CT patients who were diagnosed with COVID-19 at the University of Kansas from Apr 2020 to Jan 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (SPSS Inc, Chicago, IL). Bivariate analyses, using chi-square and t-test, and logistic regression analyses were conducted. Results: The study included 40 COVID-19 patients (72.5% Oct 2020-Jan 2021), including allogeneic HCT (n=25), autologous HCT (n=13) and CAR-T CT (n=2) with median time since HCT/CT of 12.4 (1-201.9), 37.2 (0.4-118.7), and 3.8 (2.8-4.8) months. Seventy percent were Caucasians and 17.5 were Hispanics. Primary hematologic malignancy was myeloid (37.5%), lymphoid (35%) or plasma cell disorder (27.5%). Myeloablative conditioning was performed in 65% of patients. Donors were autologous (37.5%), matched sibling (17.5%), matched unrelated (22.5%) and haploidentical (22.5%). COVID-19 was mild (42.5%), moderate (42.5%) or severe (15%). Clinical findings included pneumonia (62.5%), hypoxia (25%) and ICU admission (17.5%) while therapies included remdesivir (47.5%), convalescent plasma (40%), dexamethasone (25%) and monoclonal antibodies (17.5%). Concurrent cancer treatment, other infections and active GVHD were reported in 25% (all myeloma), 20% and 32.5% of patients. After a median follow-up of 74 days (7-269), the mortality rate was 12.5% in all patients and 20% in allo-HCT patients. Significant predictors of COVID-19 severity included allogeneic HCT, concurrent immune suppression and elevated inflammatory markers. (Table). Conclusions: Hematopoietic stem cell transplant recipients have an increased risk of mortality with COVID-19. Our findings confirm the need for vaccination prioritization, close monitoring, and aggressive treatment in HCT/CT patients.[Table: see text]


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