X-LINKED ADRENOLEUKODYSTROPHY AND HEMOPHILIA-A IN THE SAME KINDRED

Adrenoleukodystrophy (ALD; McKusick 300100) is a severe X-linked neuro degenerative disorder affecting young males. It is characterized by pr ogressive demyelination, adrenocortical insufficiency and accumulation in tissues and body fluids of saturated very long-chain fatty acids ( VLCFA) (Moser et al 1991). Interestingly, ALD kindreds also include ma les with infrequent dementia with a variety of neurological complicati ons including spasticity and gait disturbance. These later-presenting males are said to have adrenomyeloneuropathy (AMN) and have similarly elevated VLCFA levels. Wanders et al (1988) demonstrated that the prim ary defect of ALD is deficiency of a peroxisomal very long-chain fatty acyl-CoA synthetase responsible for VLCFA activation to coenzyme A es ters. Haemophilia A (HemA; McKusick 306700) is the most common inherit ed disorder of blood coagulation. This disorder is caused by a deficie ncy or abnormality of clotting factor VIII(c), a large glycoprotein wi th a relative molecular mass of 267039, and is inherited as an X-linke d trait. Haemophilia A affects 1:10000 males in all population groups; of these about 50% have factor VIII(c) levels that are less than 5% o f normal, and the remainder have levels that are between 5% and 20% of normal (Antonarakis et al 1985). The gene for factor VIII(c) has been cloned, characterized and expressed in cultured mammalian cells, and maps to the distal part of the human X chromosome at Xq28 (Purello et al 1985). In contrast, the precise genetic change in ALD is still unkn own but the gene is mapped in the same region. Several studies have sh own a high incidence of the red and green pigment gene defects in ALD families, probably indicating close linkage between these two loci in the Xq28 region (Sack et al 1989); as far as we know there is no case in the literature with association of ALD and HemA. Here we present a clinical and biochemical analysis in a large Portuguese family that is unique because of the co-occurrence of both HemA and ALD.