Metachromatic Leukodystrophy (MLD)

(also known as Mucopolysaccharidosis type 1H)

Affecting one in 50,000 people, MLD is a rare genetic disorder where the enzyme (arylsulfatase A, or "ASA"), which normally breaks down the lipid sulfatide, is missing.  The resulting build up of sulfatide in the nervous system causes progressive deterioration and eventual death.  Normally, nerve endings are covered with a myelin sheath which heals speed the communication of nerve impulses.  The sulfatide accumulation causes the myelin to break down, affecting the patient's coordination and mental development.

MLD can manifest itself at three distinct stages in life.  Type I, Late Infantile, appears between six months to two years of age.  The child will develop normally until the onset of the disease, at which point parents will first begin to notice low muscle tone.  She/he will be slow in learning to walk, or begin to stagger and fall frequently.  Eventually, the child will lose any abilities she/he had once acquired, including:  speaking, moving, and swallowing.  Eventually the child will need to be tube fed, and death usually occurs three to five years after onset.

Type II, Juvenile Form MLD, appears between age four and age twelve.  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 spend an unusual amount of time daydreaming.  This physical and mental deterioration will continue until death occurs four to six years after onset.

In Type III, Adult Form MLD, the cognitive abnormalities appear first, often causing the disease to be misdiagnosed as schizophrenia.  The patient will display personality changes:  appearing anxious, apathetic, bewildered and psychotic.  They may begin to show poor school or job performance.  Physically, they will become clumsier, have slurred speech, and become blind.  Usually death follows five to ten years after diagnosis.

Because MLD is genetic, it is difficult to cure.  Current approaches to MLD include genetic counseling for parents who are carriers of the disease.  For MLD patients, a variety of treatments have been tried.  The goal of treatment is to get the missing enzyme into the body. Unfortunately, directly injecting ASA into the bloodstream has proven unsuccessful, since the enzyme cannot make it efficiently to the brain. 

To introduce ASA into the body, both gene therapy and BMT are possibilities.  In gene therapy, researchers use a virus or some other means to place the gene that produces ASA into the patient's cells.  BMT is used to place in the body bone marrow cells from another person with the correct gene.  These marrow cells are able to travel to the brain much easier.  However for advanced patients or those with the infantile form of the disease, the outcomes have been poor. BMT is the only effective treatment currently available.  On a case-by-case basis, patients (in early stages of MLD) receiving BMT have demonstrated improved development and an increase in ASA production.