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Inherited metabolic disorders

Transplant advances and outcomes

Inherited metabolic disorders are caused by a genetic mutation, creating an enzyme deficiency that leads to an inability to break down metabolic waste products. The result is a progressive cellular accumulation of toxic substances, which damages organs, tissues and the central nervous system.

If left untreated, these disorders result in a progressive disease with neurological and psychomotor obstruction, skeletal abnormalities, and life-threatening cardiac and pulmonary complications. [1, 2] Allogeneic hematopoietic cell transplantation (HCT) can prevent this progressive deterioration by introducing enzyme-producing cells that can cross the blood-brain barrier. [3]

A study of HCT in 217 patients with Hurler syndrome found that preservation of cognitive function at the time of transplant and younger age at transplantation were major predictors for superior post-transplant cognitive development. [4]

Allogeneic HCT can treat:

  • Hurler syndrome (MPS I)
  • Hunter syndrome (MPS II) [5]
  • Maroteaux-Lamy syndrome (MPS VI)
  • Sly syndrome (MPS VII)
  • Cerebral X-linked adrenoleukodystrophy
  • Globoid-cell leukodystrophy (Krabbe disease)
  • Metachromatic leukodystrophy
  • Gaucher disease
  • Fucosidosis
  • Alpha-mannosidosis
  • Aspartylglycosaminuria
  • Mucolipidosis II (I-cell disease)
  • Wolman syndrome

Recommended timing for transplant consultation

Including Hurler syndrome, adrenoleukodystrophy and others

  • At diagnosis
  • Adrenoleukodystrophy (ALD): following the diagnosis of the cerebral form of ALD

References

  1. Domen J, Gandy K, Dalal J. Emerging uses for pediatric hematopoietic stem cells. Pediatr Res. 2012; 71(4-2): 411-417. Access
  2. Boelens JJ, Orchard PJ, Wynn RF. Transplantation in inborn errors of metabolism: current considerations and future perspectives. Brit J Haematol. 2014; 167(3): 293-303. Access
  3. Prasad VK, Kurtzberg J. Transplant outcomes in mucopolysaccharidoses. Sem Hematol. 2010; 47(1): 59-69. Access
  4. Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015; 125(13): 2164-2172. Access
  5. Kubaski F, Yabe H, Suzuki Y, et al. Hematopoietic stem cell transplantation for patients with mucopolysaccharidosis II. Biol Blood Marrow Transplant. 2017; 23(10): 1795-1803. Access
  6. NMDP and ASTCT Recommended Timing for Transplant Consultation. Download PDF 
  7. National Comprehensive Cancer Network. NCCN Guidelines. 2023. Access