Cutis laxa, fat pads and retinopathy due to ALDH18A1 mutation and review of the literature

David F.G.J. Wolthuis, Ellyze Van Asbeck, Miski Mohamed, Thatjana Gardeitchik, Elizabeth R. Lim-Melia, Ron A. Wevers, Eva Morava

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Autosomal recessive cutis laxa (ARCL) is a connective tissue disorder characterized by wrinkled, inelastic skin, frequently associated with a neurologic involvement and multisystem disease. Next generation sequencing was performed in genetically unsolved patients with progeroid features, neurological and eye involvement to assess the underlying etiology. We describe an 6 month old child, diagnosed with a novel, homozygous nonsense mutation c.2339T>C in exon 18 of the ALDH18A1 gene, and reviewed all reported P5CS patients. So far 10 patients were described with mutations in ALDH18A1. Features of our patient that have been described in literature included cutis laxa on hands and feet, visible veins on thorax and abdomen, joint laxity, failure to thrive, short stature, microcephaly, and severe developmental and speech delay. Furthermore, abnormal fat distribution, retinal abnormalities, undescended testis, and retinitis pigmentosa have never been described in ALDH18A1. Some features described as unique in ALDH18A1 have been observed in PYCR1 patients, thus suggesting that the phenotypic overlap is higher than previously shown. In conclusion, the clinical phenotype caused by ALDH18A1 mutations is diverse, with variable degree of progeria in children, but always in association with neurologic disease. We suggest genetic testing for possible ALDH18A1 mutations in all patients with progeroid features, like wrinkled or parchment-like skin, abnormal growth, especially with central nervous system involvement and microcephaly.

Original languageEnglish (US)
Pages (from-to)511-515
Number of pages5
JournalEuropean Journal of Paediatric Neurology
Issue number4
StatePublished - Jul 2014


  • ALDH18A1
  • Abnormal fat distribution
  • Cutis laxa
  • Retinopathy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology


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