Treatment of MPS VII (Sly disease) by allogeneic BMT in a female with homozygous A619V mutation

Abstract

Summary:A 12-year-old girl with Sly disease (mucopolysaccharidosis VII; ␤-glucuronidase deficiency), who is homozygous for the A619V mutation, had a successful allogeneic BMT, donored by an HLA-identical unrelated female to replace the deficient enzyme. Within 5 months after BMT, the enzyme activity of the recipient's lymphocytes increased to normal range. No signs of acute or chronic GVHD were observed. For the successive 31 months post-BMT, ␤-glucuronidase activity in her lymphocytes was maintained at almost normal levels and excretion of glycosaminoglycans in the urine was greatly diminished. Ultrastructural findings demonstrated no abnormal vacuoles and inclusion bodies in the cytoplasm of her rectal mucosal cells. Coincident with the restoration of the enzyme activity, clinical improvement was dramatic. Especially notable were improvements in motor function. The patient was able to walk alone for a long time without aid, and she even became able to ride a bicycle and take a bath. In addition, recurrent infections of the upper respiratory tract and the middle ears decreased in frequency and severity, and dyspnea on exertion, severe snoring and vertigo have substantially improved. Thus, allogeneic BMT in this patient produced a better quality of life and provided a more promising outlook.

Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII

“…Only one child (12 years old) with MPS VII has been studied following BMT. 41 The mitral and aortic valve regurgitation seen in this patient was not changed 15 months following BMT.…”

“…13 More than 270 human patients with MPS have had results of cardiovascular system evaluations published. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Of these patients, the majority did not have a specific enzyme diagnosis. However, the largest group with an identified diagnosis was MPS I (Hurler syndrome, alphal-iduronidase deficiency).…”

“…36,39,[41][42][43][44][45][46] In a 9.5-year-old MPS I child, the ventricular septal thickness and sigmoidal valve thickening were reduced. 36 In another study, a series of 16 children from 3 to 108 months of age with MPS were followed post BMT.…”

Chronic idiopathic thrombocytopenic purpura in a child with Sanfilippo type A

“…Hematopoietic Stem Cell Transplantation (HSCT) with bone marrow cells has been attempted in this population based upon positive outcomes in patients with MPS I, MPS VI and MPS VII, [8][9][10] but it failed to prevent the neurological deterioration and cognitive decline even when performed early in the disease course.…”

Long-term follow up of post-hematopoietic stem cell transplantation for Hurler syndrome: Clinical biochemical and pathological improvements

“…HSCT also shows some benefits in physical activity and growth. Those studies state that allogeneic HSCT could be potential primary care for MPS I, MPS II [7,8], and MPS VII [9].…”