Cause:Genetic, autosomal recessive, on chromosome 13
Pathophys:A chronic hepatitis. Defective copper (Cu) metabolism/excretion with deposition in liver and basal ganglia; ceruloplasm-binding defect from diminished ceruloplasmin synthesis, a chromosome 13 gene. Either hepatic or neurologic sx may predominate or exist alone
Onset age 6-50 yr; usually late childhood; hepatitis sx usually appear before age 30 yr, CNS sx usually after 30 yr. Heterozygote (single gene) prevalence = 1/200; disease prevalence = 1/30 000
Sx:Tremulousness (50% at time of dx); abdominal pain (42% at dx); dystonia (36% at dx), esp loss of fine hand motor function, eg, writing, or piano playing; excessive salivation and drooling; psychiatric sx; hepatic failure sx
Si:Kaiser-Fleischner ring (68%), brownish opacity around edge of cornea, usually seen by slit lamp only early (Ann IM 1977;86:285); hepatomegaly (50%); splenomegaly (50%); neurologic si's like resting and intention tremors (50%), dysarthria (50%) and drooling (12%), ataxia (32%), rigidity, and major psychiatric si (12%); blue nail lunulae
Portal hypertension, hypersplenism; hemolytic anemia (Ann IM 1970;73:413); proximal tubule Fanconi-like syndrome (Ann IM 1968;68:770)
Lab:
Chem:Ceruloplasmin <20 µgm %, 7% false neg, false pos in heterozygotes 10% of the time and in babies age <6 mo, or with estrogen rx (Ann IM 1977;86:285)
Uric acid decreased due to poor proximal tubule reabsorption, r/o ASA rx, Fanconi syndrome, and other renal tubular syndromes (Ann IM 1974;80:42)
Hem:Thrombocytopenia (22%)
Path:Liver bx shows chronic hepatitis or biliary cirrhosis (Nejm 1982;306:319) and Cu content:
Urine:Cu excretion/24 h >100 µgm in later stages; aminoaciduria
Rx:
Prevent by screening family members w ceruloplasmin and copper levels, or by PCR analysis (Ann IM 1997;127:21)
of disease: