title: Biochemical staging of the chronic hepatic lesions of Wilson disease.
abstract: Copper toxicity steadily affects the livers of patients with Wilson disease. However, the toxic effect of copper on serum aspartate and alanine aminotransferase levels remains to be clarified as a prerequisite for diagnostic tests. The clinical records of 33 cases were analyzed to clarify the natural history of Wilson disease. Phenotypes were simplified into hepatic, acute, and neurologic. The bio-low stage of both enzymes was less than 40 IU/L, the bio-moderate stage was intermediate between 40 and 200 IU/L, and the bio-high stage was more than 200 IU/L of either or both enzymes. Rebounded enzyme levels at the recovery period from anemia were presumed to be the chronic baselines when pre-anemic enzyme levels were not available in the acute phenotype. We investigated whether these enzyme levels may provide information useful for screening patients. The natural history of chronic Wilson disease consisted of the first increasing and second decreasing phases. The clinical courses of a 4-year-old boy and 12-year-old girl were representative of the 2 phases, respectively. All but one patient were in the decreasing phase. Negative correlations were obtained between age and enzyme level in the decreasing phase. The hepatic phenotype may be a prototype found throughout the 2 phases, and acute and neurologic phenotypes may be major complications in the bio-moderate and bio-low stages of the decreasing phase, respectively. Biochemical staging may provide a better understanding of Wilson disease when combined with phenotypes. Bio-high stage patients should be referred to a medical center for diagnosis.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katano
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Ai
authors.initials: A
authors.lastname: Hattori
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tatsumi
authors.forename: Jun
authors.initials: J
authors.lastname: Ueyama
authors.forename: Shinya
authors.initials: S
authors.lastname: Wakusawa
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Yano
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.forename: Naoki
authors.initials: N
authors.lastname: Mizutani
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D027682:Cation Transport Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004796:Clinical Enzyme Tests; D000073840:Copper-Transporting ATPases; D005260:Female; D020022:Genetic Predisposition to Disease; D006527:Hepatolenticular Degeneration / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases