Bone marrow transplantation corrects osteopetrosis in the carbonic anhydrase II deficiency syndrome

Author:

McMahon Corrina1,Will Andrew1,Hu Peiyi1,Shah Gul N.1,Sly William S.1,Smith Owen P.1

Affiliation:

1. From the Department of Paediatric Haematology, Tallaght Hospital, Dublin, Ireland; Department of Padiatric Haematology and Oncology, Manchester Children's Hospital, Manchester, United Kingdom; and St Louis University School of Medicine, St Louis, MO.

Abstract

Carbonic anhydrase II (CAII), found in renal tubules, brain, and osteoclasts, is critical in acid-base homeostasis and bone remodeling. Deficiency of CAII gives rise to a syndrome of osteopetrosis, renal tubular acidosis (RTA), and cerebral calcification with associated developmental delay. It is inherited in an autosomal recessive fashion and found most frequently in the Mediterranean region and the Middle East. We report 2 related Irish families with clinically severe CAII deficiency in whom the gene mutation has been fully elucidated. Two children, one from each family, have undergone allogeneic bone marrow transplantation because of severe progressive visual and hearing loss. The older 2 children had already developed cerebral calcification and marked visual loss at the time of diagnosis and were treated symptomatically. Post-transplantation evaluation at 2 and 3 years demonstrates histologic and radiologic resolution of their osteopetrosis with stabilization of hearing and vision. Both children remain developmentally delayed and continue to have RTA, and the older child has now developed cerebral calcification. Allogeneic bone marrow stem cell replacement cures the osteoclast component of CAII deficiency and retards the development of cerebral calcification, but it appears to have little or no effect on the renal lesions.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference21 articles.

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4. A unique mutation underlying carbonic anhydrase II deficiency syndrome in patients of Arab descent.;Fathallah;Hum Genet.,1994

5. A point mutation in exon 3 (His 107*Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement.;Soda;Hum Genet.,1996

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