Correspondence

Mevalonic Aciduria Cured by Bone Marrow Transplantation

N Engl J Med 2007; 357:1350September 27, 2007

Article

To the Editor:

Neven et al. (June 28 issue)1 discuss the use of bone marrow transplantation in the treatment of severe mevalonic aciduria. We provide additional evidence for the effective cure of mevalonic aciduria by hematopoietic stem-cell transplantation.

In February 2006, we performed hematopoietic stem-cell transplantation in an 8-year-old boy who had mevalonic aciduria associated with a polymorphism in the TNFRSF1A gene, using allogeneic bone marrow from a matched sibling. Details of the clinical features of the case and biochemical and genetic evidence for the diagnosis of the periodic fever syndrome have been reported previously.2 The patient's severe febrile episodes, which had occurred on the average of every 1 to 2 months since infancy, were resistant to 4-to-6-month trials of treatment with high-dose aspirin, prednisolone, cyclosporine, and anakinra. The use of subcutaneous etanercept led to only a temporary respite, lasting less than 6 months. However, in the 16 months since transplantation of bone marrow from an HLA-matched sister, our patient has had no further episodes of periodic fever.

The patient is now well, with stable full donor chimerism (100%). Chronic, mild, graft-versus-host disease (GVHD) limited to the skin is controlled with oral tacrolimus and topical corticosteroids. However, in contrast to the patient described by Neven et al., our patient had an early clinical course after transplantation that was complicated by severe acute GVHD (after cessation of cyclosporine on day 21 as a response to initial donor chimerism of 75%) and viral infections (adenovirus, polyomavirus type BK, varicella–zoster virus, influenza A, and rotavirus), all of which have now resolved. Despite these severe infectious and inflammatory complications, no classic periodic febrile episodes were observed. In contrast, before transplantation, minor upper respiratory tract viral infections, routine immunizations, and even exposure to cold consistently triggered periodic fevers.

Our data support the use of allogeneic bone marrow transplantation in the treatment of mevalonic aciduria associated with severe periodic fever syndrome.

Peter D. Arkwright, D.Phil.
University of Manchester, Manchester M9 7AA, United Kingdom
peter_arkwright@lineone.net

Mario Abinun, D.Sc.
Andrew J. Cant, M.D.
Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, United Kingdom

2 References

1. 1

   Neven B, Valayannopoulos V, Quartier P, et al. Allogeneic bone marrow transplantation in mevalonic aciduria. N Engl J Med 2007;356:2700-2703
   Full Text | Web of Science | Medline

2. 2

   Arkwright PD, McDermott MF, Houten SM, et al. Hyper IgD syndrome (HIDS) associated with in vitro evidence of defective monocyte TNFRSF1A shedding and partial response to TNF receptor blockade with etanercept. Clin Exp Immunol 2002;130:484-488
   CrossRef | Web of Science | Medline