14800-DvRappard

35 Metachromatic leukodystrophy: disease spectrum and approaches for treatment 2 Pitfalls in diagnosis: • Clinical pitfalls: In the initial phase of late-infantile MLD, symptoms can be similar to those found in Guillain-Barre syndrome or chronic inflammatory demyelinating polyneuropathy (CIDP). 20 The findings of reduced motor nerve conduction velocities and increased protein concentration in cerebrospinal fluid together with progressive gait abnormalities and hyperirritability can result in a wrong diagnosis, which is only revised when central nervous system signs as spasticity develop. 20 Odd behavior, depression or psychotic symptoms in adult patients are often wrongly attributed to a primary psychiatric disorder, as neurological signs usually appear later. • Low ASA activity: the diagnosis of MLD cannot exclusively be based on the level of ASA activity, due to the presence of pseudodeficiency alleles in the population. In the case of pseudodeficiency alleles, ASA activity is low, which could be mistaken for MLD whilst the pseudodeficiency alleles do not lead to symptoms. Sulfatide excretion is normal in pseudodeficiency and can help with distinguishing the two, as well as mutation analysis. This is important in families with MLD and carrying pseudodeficiency alleles. • Normal ASA activity: Patients with saposin B deficiency do suffer from MLD but have an in vitro ASA activity in the normal range. 19 In these cases, the measurement of sulfatide excretion in urine is helpful as it is elevated in saposin B deficiency. Molecular analysis of the PSAP gene can confirm the diagnosis. In vitro ASA activity is normal in these cases because it is performed in an assay with a water soluble artificial substrate, in which the hydrolysis does not depend on the presence of saposin B. 9 CURRENT TREATMENT At present, there is no curative treatment available for all patients with MLD. Hematopoietic stemcell transplantation (HSCT), gene therapy and enzyme replacement therapy have been extensively tested in mouse models. The positive results reported from the different animal studies regarding HSCT, gene therapy and enzyme therapy have led to clinical trials investigating the efficacy of these approaches. Hematopoietic stem cell transplantation (HSCT) Monocytic cells of bone marrow are able to cross the blood brain barrier, differentiate into microglial cells and deliver enzymes to oligodendrocytes and neurons to correct the enzyme deficiency. This promising procedure is at this moment the only treatment,