Psychiatry and Clinical Neurosciences (2002), 56, 649
Letter to the Editor
Wilson’s disease in psychiatric patients
Wilson’s disease (WD), an inherited disorder of
copper metabolism, is known to exhibit protean mani-
festations. In addition to hepatitis, liver cirrhosis,
hemolytic anemia, and movement disorders, psychi-
atric symptoms occur, but they are non-specific and
the diagnosis is easily missed. We report two cases of
WD-associated mental disorders, identified only after
years of futile psychiatric treatment.
Mr A, an 18-year-old Caucasian, complained of
chronic fatigue, excessive daytime sleepiness, unhap-
piness, social withdrawal, and difficulties with learn-
ing, progressively evolving over the previous 6 years.
Two years of psychotherapy had been ineffective.
He was admitted because of suicidal ideations. On
admission he showed a depressed mood, a lack of
drive and psychomotor slowing. Except for stutter-
ing and scleral icterus, the physical examination was
normal. Laboratory tests revealed a decreased ceru-
loplasmin serum level of 160 mg/L (normal range:
250–600 mg/L), an elevated free copper serum level,
elevated urine copper excretion, and elevated serum
levels of bilirubin and free hemoglobin. Wilson’s
disease and WD-related hemolysis was diagnosed.
Testing for the common mutations of the ATP7B-
(WD) gene was negative. There was no Kayser–
Fleischer ring on slit-lamp examination. After
initiation of penicillamine, urine copper excretion
increased 10-fold. On discharge, the patient was free
from psychiatric symptoms, and total daily sleep time
was reduced from 15 h to 9 h.
Ms B, a 19-year-old Caucasian, showed blunted af-
fect and delusions of persecution for the past 2 years,
and was diagnosed as suffering from schizophrenia
in another hospital. Treatment with high doses of
neuroleptics and benzodiazepines had no effect. On
admission she showed pronounced dysarthria and
was severely slowed in thinking and movements
(without rigidity). There was no Kayser–Fleischer
ring. On laboratory examination, ceruloplasmin was
low (151 mg/L) and free copper serum level was ele-
vated, suggesting WD. As in Mr A, liver biopsy
was not performed due to risk–benefit considerations.
Neuroleptic treatment was discontinued and penicil-
lamine was initiated, whereupon 24-h urinary copper
excretion increased 50-fold. During the subsequent 8
weeks there was substantial amelioration of the psy-
chomotor retardation.
Disturbances of affect, thinking, and motion are
typical of schizophrenia, but dysarthria is not. Hyper-
somnia occurs in major depression, but is more
common in organic disorders and has been reported
to be associated with WD.1 In both patients, atypical
presentation led to further investigations and finally
to the diagnosis of WD. Remarkably, both patients
lacked visible corneal copper deposits, even on
slit-lamp examination. In contrast to an accepted
opinion,2 missing Kayser–Fleischer rings do not seem
to exclude WD involving the central nervous system.
Likewise, normal neurological status and normal cere-
bral magnetic resonance imaging do not reliably rule
out WD. These cases illustrate the relevance of con-
sidering Wilson’s disease in psychiatric syndromes of
atypical presentation.
REFERENCES
1. Firneisz G, Szalay F, Halasz P, Komoly S. Hypersomnia in
Wilson’s disease: An unusual symptom in an unusual
case. Acta Neurol. Scand. 2000; 101: 286–288.
2. Scheinberg ICH. Wilson’s disease. In: Braunwald E, Fauci
AS, Kasper DL, Hauser SL, Longo DL, Jameson JL
(eds). Harrison’s Principles of Internal Medicine, 15th
edn. McGraw-Hill, New York, NY, 2001; 2274–2275.
PATRICK STILLER, md, JAN KASSUBEK, md,
CARLOS SCHÖNFELDT-LECUONA, md,
BERNHARD J. CONNEMANN, md
Department of Psychiatry III, University of Ulm, Germany
Correspondence address: Bernhard J. Connemann, Department of
Psychiatry III, University of Ulm, Leimgrubenweg 12, 89075 Ulm,
Germany. Email: bernhard.connemann@medizin.uni-ulm.de
Received 10 May 2002; accepted 3 June 2002.