Introduction

X-linked adrenoleukodystrophy (X-ALD) is a genetically determined peroxisomal disorder that affects mainly the white matter and axons of the nervous system, the adrenal cortex, and the testis, but also has cutaneous manifestations. Its incidence is about 1 in 17 000 (Bezman et al., 2001). The disorder was first described in 1923 as a disorder of children (Siemerling & Creutzfeldt, 1923), but in 1976 adult forms were also recognized which are now known to be as common as the childhood forms (Budka et al., 1976; Griffin et al., 1977). The principal biochemical abnormality of X-ALD is the accumulation of saturated very long chain fatty acids in tissues (Igarashi et al., 1976) and body fluids (Moser et al., 1999). The deficient gene (ABCD1) codes for a peroxisomal membrane protein that is a member of the ATP-binding cassette (ABC transporter superfamily) (Higgins, 1992). The gene is located at Xq28. X-ALD must be distinguished from the less frequent neonatal adrenoleukodystrophy (NALD), which has an autosomal recessive mode of inheritance and is a disorder in which the biogenesis of the peroxisome is defective (Kelley et al., 1986; Gould et al., 2001). This chapter will deal only with X-ALD.

Clinical features

Neurologic findings

The clinical manifestations of X-ALD are summarized in several recent reviews (Moser et al., 2002; Moser 1997; Aubourg, 1996; van Geel et al., 1997). As seen in Tables 31.1(1) and (b), the range of clinical expression varies widely.