Maple syrup urine disease hair reveals the importance of 18-methyleicosanoic acid in cuticular delamination.

18-Methyleicosanoic acid (18-MEA) is thought to be covalently bound to the outer surface of human hair and is a major component of the outer beta-layer of the cuticular cell membrane complex (CCMC). Cuticular delamination, whether this occurs between the outer beta- and delta-layers or within the plane of the beta-layer, results in a fresh layer of 18-MEA being exposed at the newly-revealed surface. Hair from patients with Maple Syrup Urine Disease (MSUD), however, does not contain 18-MEA and here, we report on the importance this unusual fatty acid in cuticular delamination. Hair fibres were collected from 10 patients with classic (type 1A) MSUD from a Mennonite community in Pennsylvania, USA. Included amongst these were hairs from dizygotic twins (A1 and A2), one of whom had MSUD, and the other did not; it was unknown at the beginning of the study which twin had MSUD. The outer surfaces were examined using atomic force microscopy (AFM) and transverse sections imaged using transmission electron microscopy (TEM). The newly revealed intercellular surface regions from twin A2 were found to be significantly rougher than those from twin A1. TEM studies showed the trilamellar CCMC to be continuous for twin A1, but possessed discontinuities of variable length (100-1000 nm) for twin A2. In contrast with other work, TEM showed no specific defects in the outer beta-layer. The outer cuticular surfaces for most MSUD patients showed a great abundance of residual endocuticle, although in other cases this was less pronounced. These differences may be explained by some residual activity of the branched-chain alpha-ketoacid (BCKD) dehydrogenase. Cuticular delamination in MSUD-hair probably still occurs within the general plane of the CCMC, although fracture through discontinuities of this layer results in zones of endocuticle being exposed at the new surface.