Long‐term effects of bone marrow transplantation for inborn errors of metabolism: A study of four patients with lysosomal storage diseases

Abstract

Long‐term effects of bone marrow transplantation (BMT) were evaluated in patients with I‐cell disease, metachromatic leukodystrophy (MLD), Maroteaux‐Lamy syndrome or Hunter syndrome (mild form). Donors were human leukocyte antigen (HLA)‐matched siblings, and the follow‐up periods were 24–71 months after BMT. The enzyme activities were increased in leukocytes, plasma or liver tissues compared with pre‐BMT levels. A patient with I‐cell disease acquired development of 4–8 month old infants and showed no further progression in cardiac dysfunctions. A patient with MLD showed a decelerated disease progression and an improved peripheral neuropathy, but progressive brain atrophy was not prevented. Patients with Maroteaux‐Lamy syndrome or Hunter syndrome showed improvements in hepatomegaly, joint contractures, short stature and tight skin, and this greatly increased their quality of life. These results indicated that the long‐term therapeutic effects achieved by BMT were subject to multiple factors including biochemical improvements, a reversibility of affected tissues, or advanced states of disease and central nervous system impairments in inborn errors of metabolism.

Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines

“…40,102,103 Over the past 5 years, three patients (0.3-1.7 years of age at HCT) have been transplanted at the Universirty of Minnesota. 104 The early follow-up has shown good cardiopulmonary function in two patients while one has developed pulmonary hypertension.…”

“…Reported benefits of HCT in MPS VI include enzymatic and biochemical correction, resolution of hepatosplenomegaly, stabilization of cardiopulmonary function, and improvement of visual acuity and joint mobility. 10,11, 40 All phenotypes of MPS VI are associated with reduced life expectancy and should therefore be considered candidates for HCT or ERT.…”

“…This may explain the presence of several case reports (all with relatively short follow-up), suggesting a beneficial effect from HCT. [39][40][41] However, there have also been many extremely disappointing outcomes from transplants. 23,42,43 It is the firm belief of the authors, and of many metabolic physicians experienced in following such children, that MPS II is not an appropriate indication for HCT.…”

Detection by Urinary GAG Testing of Mucopolysaccharidosis Type II in an At-Risk Spanish Population

“…Although Hunter syndrome is a rare condition, its severity makes it very important as a health problem. This is because it could cause premature death, severe neurological disorders, mental retardation and poor overall quality of life, dependency on others, institutionalisation, higher healthcare costs and, therefore, notably higher family, social and economic burdens (Imarzumi et al 1994). …”

Attenuation of ganglioside GM1 accumulation in the brain of GM1 gangliosidosis mice by neonatal intravenous gene transfer

“…BMT is effective on the somatic involvement of LSDs. 6,11 However, the uses of BMT are limited for the lack of appropriate donors, or morbidity associated with allogeneic transplantation. Moreover, bone and the brain are the exceptions to the effects of BMT.…”