Juvenile metachromatic leukodystrophy. Importance of early diagnosis and treatment.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease, due to deficient arylsulfatase A. There is no curative treatment except for early allogeneic hematopoietic stem cell transplantation. We present data on 4 patients with juvenile MLD. Three had a P426L mutation and one patient was homozygous for a C156T mutation. The clinical picture was similar including onset around 15-17 years with behavioural changes, desinhibition, followed by memory dysfunction and spastic paraparesis and polyneuropathy. The first patient was diagnosed at the age of 19 years and had already extensive cerebral white matter involvement. His younger sister (15 years) at the time of diagnosis was still asymptomatic. Both siblings had no HLA-identical or acceptable HLA-matched unrelated marrow or blood cell donor. They were both transplanted using each two unrelated umbilical cord blood units. The 19-year old patient had a follow-up of 6 months after transplant, has full donor chimerism, full haematological recovery and is neurologically stable. The third patient was diagnosed at the age of 18 years with cognitive decline and psychiatric symptoms. She had a HLA-identical unaffected sister and underwent peripheral blood cell stem transplantation (with reduced intensity conditioning) successfully. She stabilized neurologically. The fourth patient diagnosed at 20 years, had a HLA-identical unaffected brother and was treated likewise, at 22 years. She obtained stable mixed blood cell chemirism but the disease was progressive, despite donor lymphocyte infusions to improve the level of chimerism. The arylsulfatase levels of the first three patients is still short to draw definitive conclusions. It is suggested that allogeneic hematopoietic stem cell transplantation is feasible in juvenile MLD and that treatment at an early stage is more likely to be beneficial.