Genetic Diseases Treatment Options

Bone marrow transplantation (BMT) is the only known treatment for a variety of genetic diseases sometimes called "inborn errors of metabolism" or "storage diseases." These diseases are caused by a deficiency of a specific substance in the body, usually a protein, which results in the accumulation of toxic chemicals inside the cells.

Depending upon the protein abnormality and the chemicals that accumulate, specific patterns of tissue damage and organ failure occur, including:

  • Central nervous system deterioration
  • Growth failure
  • Bone abnormalities and joint disability
  • Enlargement of the liver and spleen in the abdomen
  • Heart disease
  • Airway obstruction
  • Lung disease
  • Corneal clouding
  • Hearing loss

The eventual organ damage and outcome of the different diseases is quite variable, although the ones in which BMT has been evaluated are those that have a naturally progressive downward course usually ending in death during childhood.

Bone Marrow Transplant

The purpose of a bone marrow stem cell transplant for children with these disorders is to provide special marrow-derived cells, which travel to various organs in the body including the:

  • Liver, called Kupffer cells
  • Skin, called Langerhan's cells
  • Lungs, called alveolar macrophages
  • Spleen, called macrophages
  • Lymph nodes, called lymphocytes and macrophages
  • Tonsils, called lymphocytes and macrophages
  • Brain, called microglia

The storage disease that has received the most attention is Hurler's mucopolysaccharidosis, also known as MPS I. However, many other inborn errors or storage diseases have been successfully treated with a BMT including adrenoleukodystrophy, metachromatic leukodystrophy, Krabbe's disease and Niemann-Pick. For many others, including I cell, Hunter's mucopolysaccharidosis, Sanfilippo too few have been evaluated to know for sure whether or not BMT will be helpful. There have been more than 300 patients with Hurler's disease treated by bone marrow transplantation throughout the world. In many cases, the donors have been human leukocyte antigen (HLA) matched siblings, and the conditioning regimen has utilized high doses of chemotherapy, including cyclophosphamide and busulfan.

In successfully engrafted patients, organ damage and other negative side effects are reduced. However, the long-term effect on growth and skeletal development, and the effects on existing bone disease are less defined. Of greatest significance is the effect on the central nervous system. While the damage to the brain, which has occurred up to the time of transplant is not reversed, it does appear in long-term studies that further nervous system degeneration is either prevented or at least reduced.

Unfortunately, at least 80 percent of children with a storage disease who might benefit from a bone marrow transplant will not have an HLA-matched sibling donor. Matched unrelated donors have been identified in a relatively large number of situations for children with Hurler's. In a review of 40 such patients, there was a significant graft failure rate (40 percent), which was thought to be due to abnormal metabolism of busulfan by children with Hurler's. There also was a high incidence of graft-versus-host disease (GvHD). The use of umbilical cord blood as a source of bone marrow stem cells has further increased the likelihood that a child with one of these disorders that might benefit from a transplant, but who does not have a matched relative will be able to receive treatment.

Optimizing Engraftment and Minimizing Damage

To overcome the graft failure, we have evaluated the busulfan pharmacokinetics in a large number of children undergoing BMT. We found that while children engrafted at a wide range of steady state busulfan concentrations (200 to 900), all of the graft rejections occurred at a concentration of less than 600. We have recently completed a study of targeted busulfan in which the pharmacokinetics is measured prior to admission using a test dose of busulfan. The dose is then adjusted in order to obtain a steady state concentration of 600 to 800. Because the combination of busulfan and cytoxan has been associated with significant toxicity we have further modified the conditioning regiment to replace the cytoxan with fludarabine. In this study, we are prospectively evaluating the targeted busulfan/fludarabine regimen in children with storage diseases in which the targeted level of busulfan will be fixed at 600. We believe this will optimize the chances for engraftment while minimizing complications. For more information about this specific protocol, please see Marrow Stem Cell Defect Treatment Options.


Patients with a lysosomal storage disease or other inborn error for which BMT has been performed with positive results in at least one patient are eligible for this protocol if they have a closely matched related or unrelated donor, including an umbilical cord blood donor, available. This includes the following diseases:

  • Hurler's
  • Morquio
  • Maroteaux-Lemy
  • Metachromatic Leukodystrophy
  • Globoid Cell Leukodystrophy
  • Adrenoleukodystrophy
  • Gaucher's Disease
  • Types of Niemann-Pick
  • Types of Sanfilippo
  • Hunter's Disease

In addition, patients need to have acceptable cognitive-psychosocial development, which means that:

  • The child does not have a history of pervasively and chronically delayed development reported by health care providers, parents and others who have worked with the child
  • The child has above or at the level of mild retardation on two or more standardized tests
  • Nursing and mental health care providers have observed the child's interactions with parents and health care provider and have concluded that the child can interact constructively with others, learn from experiences and adapt to situations over time
  • The parents recognize that the existing delays will not be reversed and understand the need for ongoing interventions and evaluation to chart progress
  • The child also should have sufficient heart, lung and other organ function to get through the rigors of chemotherapy administration and a stem cell transplant


Reviewed by health care specialists at UCSF Benioff Children's Hospital.

Related Information

UCSF Clinics & Centers

Blood & Marrow Transplant

Blood and Marrow Transplant Program
1975 Fourth St., Sixth Floor
San Francisco, CA 94158
Phone: (415) 476-2188
Fax: (415) 502-4867

Blood & Marrow Transplant Clinic
1825 Fourth St., Sixth Floor
San Francisco, CA 94158
Phone: (415) 353-2986
Fax: (415) 502-4867

Our Experts

Morton J. Cowan
Dr. Morton J. Cowan,
pediatric immunologst and bone marrow transplant specialist