14800-DvRappard

52 Chapter 3 In 1985, the first hematopoietic cell transplantation (HCT) for MLD was performed in the USA. 4 As for other lysosomal storage disorders, HCT is supposed to be effective because donor macrophages, a source of lysosomal enzymes, migrate to the recipient’s brain to produce the missing enzyme there, cross-correcting the deficiency. Since then, treatment has greatly been optimized by reduced conditioning regimens, decreased treatment related mortality (now estimated at less than 10% for children), the usage of umbilical cord cells and better knowledge about correct timing. The decision whether HCT is appropriate is based on cognitive function (IQ>75) and neurological examination (able to walk without support). HCT has now been proven to be able to halt or even prevent the disease, but only when performed before disease is too advanced. 5 This is mainly due to the fact that it takes 6 to 12 months after transplantation until donor cells become effective, months in which the disease still progresses. This underlines the essence of timely diagnosis, as exemplified by 4 cases. Case reports Patient 1 (MLD-58) had typical motor and cognitive development, but always problems with social interaction. His premorbid IQ (age 9), was in the superior range (verbal IQ 119, performance IQ 130 on the Wechsler Intelligence Scale for Children-III (WISC- III)). At age 12, his school performance dramatically declined, from regular to special education within one year, leading to the diagnosis of Asperger syndrome. Eventually, his behavior became so aggressive and disinhibited that admission to a psychiatric ward was necessary at age 13. His motor function remained typical. Coinciding with an exacerbation of behavioral problems, a discrepancy between performance (81) and verbal (111) IQ (WISC-III) led to referral to a neurologist. MRI, at age 13, revealing white matter abnormalities suggesting MLD, which was confirmed by biochemical and genetic analyses. Despite the delay between first symptoms and diagnosis, he was still a candidate for HCT with a total IQ of 92 and only minor abnormalities at neurological examination. Now, 2.5 years after HCT, his cognitive abilities have stabilised after an initial further decline (verbal IQ (73), performance IQ (65)). Motor function remained typical. His behavioral problems, treated with risperidone since age 13, are now well controlled. Patient 2 (MLD-60) had a typical early development. At 8 years, her cognitive function gradually declined; she could no longer learn new tasks and even lost previously gained skills as reading, resulting in special education. Her behavior became increasingly aggressive and disinhibited. The diagnosis attention deficit and hyperactivity disorder (ADHD), was made, for which she was treated with methylphenidate and risperidone. At age 12 she developed repetitive motor and vocal tics. Her IQ was tested after