14800-DvRappard

16 Chapter 1 nodes and ovaries. 24 The accumulation of sulfatides in the kidney leads to an increased sulfatide excretion in urine in patients, which is further described in the discussion of this thesis. CLINICAL SPECTRUM The three clinical subtypes vary in disease progression and prevailing symptoms. The late-infantile form starts before 30 months of age. First symptoms are usually psychomotor regression resulting in ataxia, weakness and areflexia. 1 The juvenile form starts between 30 months and 16 years and usually presents with a combination of motor regression (due to ataxia, a pyramidal syndrome and peripheral neuropathy), behavioral abnormalities and deterioration in school performance. The adult form starts after the age of 16 years with behavioral and intellectual changes. 11,25 Peripheral neuropathy follows as the disease progresses but remains mild in most cases. Beyond infancy, peripheral neuropathy as presenting sign is uncommon. In general, the earlier the disease onset, the faster it progresses. In the late-infantile form, language regression usually occurs one year after onset, and complete loss of speech before the age of 3 years. 26 Kehrer and colleagues observed loss of any communication in half of the late-infantile patients 3 years after onset. Complete regression of gross motor function takes on average 15 months after the first signs of motor deterioration. 27 In juvenile patients, a complete loss of language occurs around 6 years after disease onset in most patients, and complete loss of any communication nine years after onset in a quarter of patients. The deterioration of gross motor function has a similar pace; the loss of complete motor function takes approximately 6 years after first signs of regression of motor function. 27 Eventually, all acquired skills are lost and patients die. In the juvenile and adult form, psychiatric symptoms can precede overt neurological signs, sometimes by years. This makes obtaining a correct diagnosis challenging, which we further describe in chapter 3.