Inherited Metabolic Disorders

Our pediatric BMT program is an international leader in transplantation of patients with IMSD. Since 1982, University physicians have performed over 300 transplants for these rare and otherwise fatal diseases.

What are Inherited Metabolic Storage Diseases?

The IMSDs are a diverse group of disorders resulting from an inherited deficiency or defect of a single enzyme or protein.  These diseases are often characterized by progressive brain and nerve deterioration.  Depending upon the specific disease, other body systems can be involved, such as the heart, bones, lungs, ears, nose and throat.  The IMSDs include the mucopolysaccharidoses (MPS), such as Hurler and Maroteaux-Lamy syndromes; the leukodystrophies such as Adrenoleukodystrophy (ALD), Metachromatic Leukodystrophy (MLD), and Globoid Leukodystrophy (GLD), and other storage diseases, such as alpha-mannosidosis, fucosidosis, and I-cell disease. 

Metabolic Storage Diseases We Treat with BMT

As expertise with blood and marrow transplants has increased, this treatment has been applied to a wider variety of disorders, including some which are not cancer-related or diseases that affect the bone marrow.

At the University of Minnesota, we have pioneered the use of blood and marrow transplants as treatment for patient with Adrenoleukodystrophy (ALD), Metachromatic leukodystrophy (MLD), or Globoid Cell leukodystrophy (GLD), also called Krabbe Disease.  In addition, transplants are used to treat metabolic “storage” diseases, such as Hurler syndrome and Maroteaux-Lamy syndrome.

While these disorders have their own characteristic challenges and complications, they are alike in their ability to cause severe, progressive neurologic deterioration and because they are inherited conditions genetically resulting in the deficiency of a single enzyme.

Blood or marrow transplant from a normal donor (an unaffected HLA-matched family, unrelated donor or unrelated cord blood) can provide replacement of the missing enzyme through the production of healthy white blood cells providing the missing enzyme.  In the presence of a source of enzyme the accumulated abnormal material can be cleansed, and the clinical features of the disease arrested or reversed.  The indications for transplant in each disease vary.

• Adrenoleukodystrophy (ALD)
• Metachromatic leukodystrophy (MLD)
• Globoid Cell leukodystrophy (GLD), also called Krabbe Disease or galactocerebrosidase deficiency
• Hurler syndrome, also called Mucopolysaccharidosis type IH, MPS I, Hurler's
• Maroteaux-Lamy syndrome
• Fucosidosis fucosidase deficiency
• Wolman disease, also called acid lipase deficiency
• Niemann-Pick disease
• GM1 gangliosidosis
• Tay Sachs disease
• Sandhoff disease
• Alpha Mannosidosis
• I-cell disease, also called mucolipidosis type II

Leading Research Collaboration

Collaboration with other institutions and researchers is essential to understand which treatments are most promising in these rare diseases.  The International Storage Disease Collaborative Study Group, an international group of researchers and clinicians dedicated to advancing treatment for inherited metabolic storage diseases through collaborative studies and data sharing is based at the University of Minnesota.

Scientists from the University of Minnesota’s Stem Cell Institute, Comprehensive Cancer Center and Medical School provide additional expertise in the areas of stem cell biology, genetics, gene therapy, immunotherapy and immunology to provide our patients with access to the latest technology in treating these diseases. 

IMSD Comprehensive Care Program Team

Medical Team
Dr. Paul Orchard, Assistant Professor and Medical Director of IMSD Program,  specializes in transplanting patients with inherited genetic diseases.  His laboratory is studying genetic engineering to improve transplant outcomes.

Dr. Jakub Tolar, Assistant Professor, focuses on basic biology of metabolic storage diseases and the implications for individuals with these diseases, as well as patient care.

 

Specialists and Health Professionals

IMSD patients have complex medical needs requiring the attention of multiple medical subspecialists.  Our patients are evaluated, treated and followed long-term by an individually tailored multidisciplinary team of experts that focuses on the unique needs of IMSD patients.  Specialty areas include:  neurology, neuropsychology, cardiology, orthopedic surgery, pulmonary, anesthesiology, endocrinology, genetic counseling, audiology, ENT, pharmacology and ophthalmology. 

The IMSD Program Comprehensive Care Team also includes a specially trained team of health professionals to coordinate the care of our patients from referral through treatment and long-term follow-up.  These health professionals include:  pediatric nurse practitioners/physician assistants, nurse coordinators, research nurse clinicians, nurses, social workers, therapists, and child family life specialists.

 

Why is Comprehensive Care Important?

Inherited metabolic storage disease patients have complex medical conditions that usually involve multiple organ systems.  Early diagnosis and treatment is essential to minimize irreversible organ damage caused by the disease.  Comprehensive care is focused on correcting the underlying genetic problem but also addresses the medical, psychological and emotional problems that accompany these diseases.  This approach includes diagnosis, evaluation, treatment and follow-up by a coordinated team of medical specialists, specially trained medical and health care professional s and therapists.  Because of the success of this approach, the IMSD Comprehensive Care Program at University of Minnesota Medical Center, Fairview serves as a national referral center for diagnosis, monitoring and treating IMSD patients.  Our combined research experience, long-term follow-up database, and established collaborative relationships with specialists experienced in treating IMSD patients makes our program one of the most comprehensive BMT programs in the world and helps us meet our goal to provide each patient and their family with the best quality of life possible.

Treatment for IMSD

Inherited metabolic storage disease patients referred to University of Minnesota Medical Center, Fairview are assessed by our IMSD Team to customize a treatment plan based upon the patient’s diagnosis and stage of disease.  In some cases this means monitoring the disease using serial brain scans, enzyme measurements and other tests until it is clear that the time for BMT is right.  In other cases, immediate BMT is the best course of action.  BMT provides healthy cells that can produce the missing enzyme or protein leading to the normalization of cell processes.  To date, BMT is the only treatment available that stops progression of these diseases.  Early detection and intervention is key to a successful outcome. 

Through our long-term follow-up program, we monitor IMSD patients long after BMT to ensure an optimal quality of life for infants, children, adolescents, and adults.

Participation in clinical trials may be another option, one that offers therapy not generally available through standard medical channels.  Your primary care physician will discuss the treatment options available to you and your family so that you can make an informed decision.

Research

Although BMT is currently the only available therapy that stabilizes the progressive nature in a variety of IMSDs, University of Minnesota researchers are developing other novel therapies to treat these diseases, including:

• Enzyme replacement therapy, either alone or in conjunction with BMT, to improve outcomes and reduce transplant related complications.

• Using a different type of cell with BMT (called multipotent adult progenitor cells or MAPCs) to help regenerate brain, nerve and bone cells. 

• Gene therapy and genetic engineering using molecular biology tools to replace a defective gene with a healthy gene, or to insert a piece of DNA into transplanted cells to make the BMT procedure more effective and safer. 

For more information about this program, contact Paul Orchard, M.D. at email, orcha001@umn.edu or 612.626.2961.