Diseases We Treat
Leukodystrophy patients travel from all around the world to be treated by our physicians.
Inherited leukodystrophies are rare disorders that affect lysosomes or peroxisomes, which are small organelles within cells. Normally, nerve endings are covered with a myelin sheath which helps speed the communication of nerve impulses. If myelin is lost, the underlying nerve cell will become dysfunctional. The areas within the brain that contain large amounts of myelin are called white matter. It is these locations that are affected by the disorders called leukodystrophies. In many of these diseases, the myelin around the peripheral nerves are also affected. The inherited leukodystrophies include adrenoleukodystrophy (ALD), globoid cell leukodystrophy (GLD), metachromatic leukodystrophy (MLD), Sandhoff disease, Tay Sachs disease, GM1 gangliosidosis and others. Most commonly, these disorders are progressive and fatal without intervention.
The University of Minnesota is an international leader in the use of bone marrow transplantation for leukodystrophies. The National Marrow Donor Program's transplants-by-disease chart for Inherited Metabolic Disorders is a helpful resource that compares our experience to other transplant centers.
Adrenoleukodstrophy (ALD) is a rare genetic disorder that affects males. It’s characterized by the inability of the body to break down "very long chain fatty acids" (VLCFA). The resulting build-up of VLCFA can cause dysfunction of the adrenal glands, testes and the central nervous system by breaking down the myelin sheaths that protect nerves. Normally, nerve endings are covered with a myelin sheath which helps speed the communication of nerve impulses. If myelin is lost, the underlying nerve cell will become dysfunctional. When this breakdown occurs in the brain, it’s known as cerebral ALD (cALD), which often causes rapidly progressive neurologic deterioration and eventual death.
Parents of children with cALD typically begin to notice behavioral changes, such as hyperactivity, poor performance in school, and short attention span.
Nearly 40 percent of ALD cases are the cerebral form of ALD which begins during childhood, usually between the ages of 4 and 8. The only effective treatment for cALD is a blood and marrow transplant (BMT), which can halt progression of myelin loss.
Globoid leukodystrophy (GLD) is also known as Krabbe disease. It is a degenerative disorder that affects the nervous system. It is caused by the shortage (deficiency) of an enzyme called galactosylceramidase, also known as galactocerebrosidase. This results in a build-up of storage material in the brain and nerves, leading to a loss of myelin. Normally, nerve endings are covered with a myelin sheath which helps speed the communication of nerve impulses. The lack of enzyme activity causes the myelin to break down, affecting the patient's development.
Classic GLD manifests itself in infants between 3 and 6 months old. The child will develop normally until the onset of the disease, at which point parents will first begin to notice the child is extremely irritable. Other initial symptoms may include frequent fevers, difficulty keeping food down, stiffness in the limbs, and frequent seizures. Affected infants also experience vision loss. Because GLD progresses quickly, these patients need to receive BMT treatment very early in their disease progression in order to be effective.
Less commonly, onset of Krabbe disease can occur in childhood, adolescence, or adulthood (late-onset forms). Visual problems, behavioral changes and walking difficulties are the most common initial symptoms in this form of the disorder, however, signs and symptoms vary considerably among affected individuals.
Metachromatic Leukodystrophy (MLD) is a rare genetic disorder where the enzyme arylsulfatase-A ("ARSA"), which normally breaks down the lipid sulfatide, is missing. The resulting build-up of sulfatide in the central nervous system and peripheral nervous system causes progressive loss of myelin. Normally, nerve endings are covered with a myelin sheath which helps speed the communication of nerve impulses and protects the underlying nerve cell. The accumulation of sulfatide causes the myelin to break down, affecting the patient's coordination, strength and cognition.
There are three types of MLD. The first is known as Late Infantile MLD, which generally appears between 6 months and 2 years of age. The child will develop normally until the onset of the disease, at which point parents will first begin to notice a change in gross motor skills. The child may be delayed in learning to walk, or begin to stagger and fall frequently. Eventually, the child will lose any abilities that she or he had once acquired, including speaking, moving and even swallowing.
The second type, Juvenile Form MLD, typically appears between ages 4 and 12. The disease first affects the ability to walk and the child's posture. Mentally, the child will have emotional difficulties, have trouble following directions, develop abnormal behaviors, and begin to experience academic difficulties.
Individuals with the third type, Adult Form MLD, will begin to show symptoms between the teenage years and 40. Cognitive and behavioral abnormalities appear first, often causing the disease to be misdiagnosed as schizophrenia or mental illness. The patient will display personality changes- appearing anxious, apathetic, disorganized, or bewildered- and demonstrate declining memory skills. Physically, they may become clumsier. The progression of Adult Form MLD follows the same pattern as Type 2, but at a slower rate.
Although the Late Infantile variant is particularly devastating, all forms of MLD if untreated will lead to neurologic deterioration and ultimately death.