Autosomal recessive cutis laxa type IIIA: Report of a patient with severe phenotype and review of the literature

Abstract

Autosomal recessive cutis laxa type IIIA is a very rare genetic condition, caused by pathogenic variants in ALDH18A1, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS). This enzyme catalyzes the reduction of glutamic acid to delta1-pyrroline-5-carboxylate, playing a key role in the de novo biosynthesis of proline, ornithine, and arginine. Autosomal recessive cutis laxa type IIIA is characterized by abundant and wrinkled skin, skeletal anomalies, cataract or corneal clouding and neuro-developmental disorders of variable degree.We report on a patient with autosomal recessive cutis laxa type IIIA, due to a homozygous missense c.1273C > T; p. (Arg425Cys) pathogenic variant in ALDH18A1. The patient presented a severe phenotype with serious urological involvement, peculiar cerebro-vascular abnormalities and neurodevelopmental compromise. This description contributes to better characterize the phenotypic spectrum associated with ALDH18A1 pathogenic variants, confirming the systemic involvement as a typical feature of autosomal recessive cutis laxa type IIIA.