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

Licia Lugli; Francesca Cavalleri; Emma Bertucci; Björn Fischer-Zirnsak; Giulia Cinelli; Viola Trevisani; Cecilia Rossi; Marika Riva; Lorenzo Iughetti; Alberto Berardi

doi:10.1016/j.ejmg.2022.104568

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

Eur J Med Genet. 2022 Sep;65(9):104568. doi: 10.1016/j.ejmg.2022.104568. Epub 2022 Jul 13.

Authors

Affiliations

¹ Neonatology Unit, Mother-Child Department, University Hospital of Modena, Italy. Electronic address: lugli.licia@aou.mo.it.
² Neuroradiology Unit, University Hospital of Modena, Italy.
³ Obstetric-Gynecology Unit, Mother-Child Department, University Hospital of Modena, Italy.
⁴ Institute of Medical Genetics and Human Genetics, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany.
⁵ Postgraduate School of Pediatrics, Department of Medical and Surgical Sciences for Mother, Children and Adults, University of Modena and Reggio Emilia, Italy.
⁶ Neonatology Unit, Mother-Child Department, University Hospital of Modena, Italy.
⁷ Pediatric Unit, Mother-Child Department, University Hospital of Modena, Italy.
⁸ Postgraduate School of Pediatrics, Department of Medical and Surgical Sciences for Mother, Children and Adults, University of Modena and Reggio Emilia, Italy; Pediatric Unit, Mother-Child Department, University Hospital of Modena, Italy.

PMID: 35842092
DOI: 10.1016/j.ejmg.2022.104568

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.

Keywords: ALDH18A1; Autosomal recessive; Cutis laxa; P5CS.

Publication types

Review

MeSH terms

Cutis Laxa* / pathology
Homozygote
Humans
Phenotype
Proline

Substances

Proline

Supplementary concepts

Cutis Laxa, Autosomal Recessive, Type I