Hairs from patients with maple syrup urine disease show a structural defect in the fiber cuticle.

Models for the surface of cuticle cells in hair fibers consist of a monolayer of fatty acids covalently bound to the underlying protein membrane by thioester linkages. The most prominent of these fatty acids is 18-methyleicosanoic acid (C21a), the synthesis of which requires the oxidative decarboxylation of isoleucine. Maple syrup urine disease (MSUD) is caused by an inherited deficiency in the enzyme branched chain 2-oxo acid dehydrogenase, which leads to the accumulation of branched chain alpha-keto-acids derived from the amino acids, leucine, isoleucine, and valine. Transmission electron microscopy studies of developing hair fibers show a structural defect in the fiber shaft in hair from patients with MSUD. This defect is confined to the cuticle of the fiber, where the cuticle membrane directly apposes the intercellular material. Thus, the defect indicates that C21a is located exclusively on the upper surface of fiber cuticle cells. Lipid analysis of MSUD hairs has demonstrated significant changes in the relative abundance of the covalently bound fatty acids and an almost complete absence of C21a, whereas there was little difference in the amino acid composition compared with normal hair. These results provide further evidence for the existence of the surface lipid monolayer and its crucial role in cellular adhesion.