Current state of Wilson disease patients in central Japan.
OBJECTIVE
This study evaluated the current state of patients with Wilson disease in central Japan.


METHODS
Between 1999 and 2007, 30 patients were diagnosed as having Wilson disease with an International Diagnostic Score of 4 or more. The phenotypes, genotypes and post-diagnostic courses of these patients were analyzed.


RESULTS
Twenty-six patients had ATP7B mutations responsible for Wilson disease. Four patients had a single mutant chromosome. There were 2 major mutations of 2333 G>T and 2871 delC (40%), and 6 novel mutations (13%) in our patients. The first clinical manifestation was the hepatic form in 22, neurological form in 5, and hemolysis in 3 patients. The hepatic form was diagnosed around the age of 13 years, followed by neurological complication with a time lag of 9 years. Thus, some patients, especially patients with the neurological form, did not undergo early diagnostic tests including ATP7B analysis. During the post-diagnosis period, 3 patients were hospitalized for recurrent liver disease, and 2 patients committed suicide. One female patient died from acute hepatic failure associated with encephalopathy after fertilization therapy, while 2 male patients recovered from encephalopathy-free, prolonged hepatic failure after noncompliance with drug therapy. The King's Scores for liver transplantation were below the cut-off in both cases.


CONCLUSIONS
To minimize delayed diagnosis, ceruloplasmin determination and ATP7B analysis may be recommended to patients showing hepatic damage of unknown etiology. At gene diagnosis, appropriate management of patients including compliance education and emotional care to prevent suicide might be important.
Tatsumi
Yasuaki
Y
Department of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya.
Hattori
Ai
A
Hayashi
Hisao
H
Ikoma
Jiro
J
Kaito
Masahiko
M
Imoto
Masami
M
Wakusawa
Shinya
S
Yano
Motoyoshi
M
Hayashi
Kazuhiko
K
Katano
Yoshiaki
Y
Goto
Hidemi
H
Okada
Toshihide
T
Kaneko
Shuichi
S
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D027682:Cation Transport Proteins / Q000235:genetics*; D015913:Chelation Therapy / Q000379:methods; D002648:Child; D015331:Cohort Studies; D057210:Delayed Diagnosis; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D005820:Genetic Testing; D006527:Hepatolenticular Degeneration / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D017114:Liver Failure, Acute / Q000175:diagnosis / Q000401:mortality*; D008297:Male; D011379:Prognosis; D011618:Psychotic Disorders / Q000175:diagnosis / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D013406:Suicide, Attempted / Q000706:statistics & numerical data*; D015996:Survival Rate; D055815:Young Adult
D027682:Cation Transport Proteins