title: A case of severe osteomalacia caused by Tubulointerstitial nephritis with Fanconi syndrome in asymptomotic primary biliary cirrhosis.
abstract: BACKGROUND
  Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC.
  
  
  METHODS
  We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated the features of tubulointerstitial nephritis (TIN). The patient was also suspected as having primary biliary cirrhosis (PBC) because of high levels of alkaline phosphatase, IgM and the presence of anti-mitochondrial M2 antibody, though biochemical liver function was normal. Sequential liver biopsy was compatible with PBC and the diagnosis of PBC was definite. After administration of 1,25 dihydroxyvitamin D3, neutral potassium phosphate, sodium bicarbonate for osteomalacia and subsequent predonizolone for TIN, symptoms of fractures were relieved and renal function including Fanconi syndrome was ameliorated.
  
  
  CONCLUSIONS
  In this case, asymptomatic PBC was shown to induce TIN with Fanconi syndrome with dysregulation of electrolytes and vitamin D metabolism, which in turn led to osteomalacia with multiple fractures. Osteomalacia has not been recognized as a result of the renal involvement of PBC. PBC and its rare complication of TIN with Fanconi syndrome should be considered in adult patients with unexplained osteomalacia even in the absence of liver dysfunction.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. syamaguc@dom.wustl.edu.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. maruyama@z7.keio.jp.|Center for Clinical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. maruyama@z7.keio.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. shuwakino@z8.keio.jp.
authors.forename: Shu
authors.initials: S
authors.lastname: Wakino
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. hirobumitokuyama@aol.com.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tokuyama
authors.affiliation: Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. akino@mbd.ocn.ne.jp.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hashiguchi
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. shinichiro.tada@daiwa.co.jp.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tada
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. homma888@gmail.com.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Homma
authors.affiliation: Medical education Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. monkawa@z5.keio.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Monkawa
authors.affiliation: Medical education Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. james.thomas@a3.keio.jp.
authors.forename: James
authors.initials: J
authors.lastname: Thomas
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. miyakaz@z6.keio.jp.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Miyashita
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. i-kuri@dc4.so-net.ne.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Kurihara
authors.affiliation: Apheresis and Dialysis Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tayoshida-npr@umin.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. yiu60553@nifty.com.
authors.forename: Konosuke
authors.initials: K
authors.lastname: Konishi
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. khayashi@tdc.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Apheresis and Dialysis Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. matuhiko@z3.keio.jp.
authors.forename: Matsuhiko
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. hiito@z8.keio.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D003937:Diagnosis, Differential; D005198:Fanconi Syndrome / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D005260:Female; D000069076:Fractures, Multiple / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D010018:Osteomalacia / Q000175:diagnosis* / Q000209:etiology* / Q000628:therapy; D016896:Treatment Outcome