Cystinuria and cystinosis are usually related to L-cystine: is this really the case for cystinosis? A physicochemical investigation at micrometre and nanometre scale
Dominique Bazin, Marion Rabant, Jérémie Mathurin, Margaux Petay, Ariane Deniset‐Besseau, Alexandre Dazzi, Yangyang Su, Etienne Paul Hessou, Frederik Tielens, Ferenc Borondics, Marine Livrozet, Élise Bouderlique, Jean‐Philippe Haymann, Emmanuel Letavernier, Vincent Frochot, Michel Daudon
Abstract
Medical literature indicates clearly that cystinuria and cystinosis, two severe genetic pathologies, are related to the presence of abnormal L-cystine deposits. While L-cystine adopts a hexagonal crystal morphology consistent with its crystallographic structure (hexagonal, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi mathvariant="normal">P</mml:mi> <mml:msub> <mml:mn>6</mml:mn> <mml:mn>1</mml:mn> </mml:msub> <mml:mn>22</mml:mn> </mml:mrow> </mml:math> space group), abnormal deposits related to cystinosis display a rectangular shape. Because this is unexpected from the hexagonal crystallographic structure of L-cystine, we have investigated this inconsistency using SEM (scanning electron microscopy) and IR (infrared) spectroscopy at micrometre and nanometre scales. Our data clearly indicate the presence of both L-cysteine and L-cystine. Considering that L-cysteine crystals display a rectangular shape, and that a transition phase between L-cysteine and L-cystine is well known, we propose the following model for deposit evolution in cystinosis. The initial abnormal deposit consists of L-cysteine, with a rectangular crystal morphology. The micrometre scale rectangular crystallite shape is retained after the phase transition equilibrium between L-cysteine and L-cystine is established, with some crystalline L-cysteine still remaining.