title: Clinical and genetic features of lysinuric protein intolerance in Japan.
abstract: BACKGROUND
  Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder affecting the transport of cationic amino acid caused by mutations in solute carrier family 7 amino acid transporter light chain, y+L system, member 7 (SLC7A7). This disorder occurs worldwide, especially in Finland and Japan, where founder effect mutations have been reported. Detailed features of the clinical symptoms and mutation types in Japanese LPI, however, remain unclear to date.
  
  
  METHODS
  An epidemiological nationwide survey of LPI patients was carried out via mail to all domestic university and general hospitals in Japan. Next, the clinical information for each LPI patient was obtained, in the form of a questionnaire, from the attending physicians who replied to the letters.
  
  
  RESULTS
  We received answered questionnaires for 43 LPI patients in 19 hospitals. We selected 35 patients who were genetically diagnosed with LPI. The most common clinical manifestations were with protein aversion, ferritinemia, increased serum lactate dehydrogenase, and hyperammonemia. The most frequent SLC7A7 mutation in Japanese LPI patients is p.R410*, which is a founder effect mutation in northern Japan. In total, nine types of mutation were detected in this survey, six of which (p.R410*, p.S238F, c.1630delC, p.S489P, c.1673delG, and IVS3-IVS5del9.7 kb) have not been reported in other countries.
  
  
  CONCLUSIONS
  The clinical and genetic features of 35 Japanese patients with LPI were characterized, and no correlation between genotype and phenotype was observed. The importance of early diagnosis for better prognosis of LPI is emphasized.
authors: Department of Pediatrics, Akita University Graduate School of Medicine, Akita City, Akita, Japan. atsuko@doc.med.akita-u.ac.jp.
authors: Atsuko
authors: A
authors: Noguchi
authors: Department of Pediatrics, Kumamoto University Hospital, Kumamoto City, Kumamoto, Japan.
authors: Kimitoshi
authors: K
authors: Nakamura
authors: Department of Metabolism, Chiba Children's Hospital, Chiba City, Chiba, Japan.
authors: Kei
authors: K
authors: Murayama
authors: Department of Pediatrics, Chiba University Hospital, Chiba City, Chiba, Japan.
authors: Shigenori
authors: S
authors: Yamamoto
authors: Department of Pediatrics, National Hospital Organization Maizuru Medical Center, Maizuru City, Kyoto, Japan.
authors: Hiroshi
authors: H
authors: Komatsu
authors: Department of Pediatrics, Yokosuka Kyosai Hospital, Yokosuka City, Kanagawa, Japan.
authors: Rika
authors: R
authors: Kizu
authors: Division of Emergency and General Medicine, Chiba Children's Hospital, Chiba City, Chiba, Japan.
authors: Masaki
authors: M
authors: Takayanagi
authors: National Center for Child Health and Development, Center of Lysosomal storage diseases, Setagaya, Tokyo, Japan.
authors: Torayuki
authors: T
authors: Okuyama
authors: Department of Pediatrics, Kumamoto University Hospital, Kumamoto City, Kumamoto, Japan.
authors: Fumio
authors: F
authors: Endo
authors: Morioka Children's Hospital, Morioka City, Iwate, Japan.
authors: Yuhei
authors: Y
authors: Takasago
authors: Sakura Pediatric Clinics, Akita City, Akita, Japan.
authors: Yutaka
authors: Y
authors: Shoji
authors: Department of Pediatrics, Akita University Graduate School of Medicine, Akita City, Akita, Japan.
authors: Tsutomu
authors: T
authors: Takahashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D027182:Amino Acid Transport System y+ / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010641:Phenotype; D055815:Young Adult
chemical_list: D027182:Amino Acid Transport System y+; C118895:SLC7A11 protein, human; D004247:DNA
keywords: SLC7A7; cationic amino acid; hyperammonemia; lysinuric protein intolerance; y+L amino acid transporter-1