title: ALDH18A1-related cutis laxa syndrome with cyclic vomiting.
abstract: Cutis laxa (CL) syndromes are connective tissue disorders characterized by redundant, sagging, inelastic and wrinkled skin, with organ involvement. Here, we describe a patient with ALDH18A1-related CL who developed cyclic vomiting. The patient was a 12-year-old boy who presented with poor postnatal growth, hypotonia, short stature, joint hyperlaxity, microcephaly, strabismus, bilateral cataracts, facial dysmorphism and severe mental retardation. Bone radiographs showed osteopenia and osteoporosis, and magnetic resonance angiography showed marked kinking and tortuosity of the brain vessels. These findings were clinically compatible with ALDH18A1-related CL. Molecular analysis revealed a de novo heterozygous mutation (p.R138Q) in ALDH18A1. No mutations were found in PYCR1 gene. The patient developed cyclic vomiting with decreased blood levels of ornithine, citrulline, arginine and proline without hyperammonemia and other hypoaminoacidemias were also found. ALDH18A1 encodes Δ(1)-pyrroline-5-carboxylate synthase, which is related to the biosynthesis of ornithine, citrulline, arginine, and proline. Cyclic vomiting has never been reported in other ALDH18A1-related CL patients. This is the first case report of ALDH18A1-related CL with cyclic vomiting associated with amino acid abnormalities.
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Shiga, Japan. Electronic address: nozaki-kgw@umin.ac.jp.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Nozaki
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusunoki
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Miya
authors.affiliation: Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Shiga, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Shiga, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Shiga, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujii
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D001774:Blood Chemical Analysis; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging; D002648:Child; D003483:Cutis Laxa / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D003937:Diagnosis, Differential; D005145:Face / Q000002:abnormalities; D005532:Foot Deformities, Congenital / Q000235:genetics / Q000473:pathology; D006228:Hand Deformities, Congenital / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D013577:Syndrome; D014839:Vomiting / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*
chemical_list: C000596432:ALDH18A1 protein, human; D000444:Aldehyde Dehydrogenase
keywords: ALDH18A1; Cutis laxa syndrome; Cyclic vomiting; P5CS; R138