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Polymorphism Of Psychiatric Symptomatology In Wilson's Disease / Polimorfismul simptomatologiei psihiatrice in Boala Wilson - Lidia Nica Udangiu, Costin Emilian Roventa

 Lidia Nica Udangiu *, Costin Emilian Rovenţa**

 

Abstract

  Wilson’s disease is a genetically transmitted autosomal – recessive disease, whose physiopathological expression is the decrease or absence of the transport of copper in the gall bladder and its consecutive buildup mainly  in the liver or in the central nervous system. Psychiatric manifestations are polymorphous, and four types were identified: cognitive impairment, behavioral symptoms, a manic-depressive affective syndrome or a schizophrenia-like syndrome. The prognosis of the psychiatric manifestations is good, with recovery beginning after 5-6 months up to 24 months of specific treatment. We shall present the case of a patient with the onset of the simptomatology in 2004 and the evidence of the disease five years later.

Keywords: Autosomal-Recessive Disease, Kayser-Fleischer ring, schizophrenia-like syndrome

 

Rezumat

Boala Wilson este o boală genetică cu transmitere autosomal-recesivă având ca expresie fiziopatologică diminuarea sau absenţa transportului cuprului în bilă şi acumularea consecutivă în organism, în special în ficat sau la nivel cerebral. Manifestările psihiatrice sunt polimorfe, fiind identificate 4 tipuri: tulburări cognitive, tulburări comportamentale, sindrom maniaco-depresiv sau sindrom schizophrenia-like. Prognosticul manifestărilor psihiatrice este bun, îmbunătăţiri apar după 5-6 luni de tratament şi continuă până la 24 luni. Vom prezenta cazul unei paciente cu debutul simptomatologiei în anul 2004 şi diagnosticarea afecţiunii cinci ani mai târziu.

            Cuvinte cheie: boală autosomal-recesivă, inel Kayser-Fleischer, sindrom schizophrenia-like

 

*Prof. Dr. - Psychiatry Hospital Pr. Dr. ‘Alexandru Obregia’ Bucharest

**Resident MD – Psychiatry Hospital Pr. Dr. ‘Alexandru Obregia’ Bucharest, croventa@yahoo.com

 

 

Wilson’s disease is a rare disease, with autosomal-recessive transmission, caused by the loss of the adenosine triphosphatase (ATP7B/WDNP), as a result of insertion or deletion of the ATP7B gene located on the chromosome 13 q14.3-q21.1. The prevalence of the heterozygote form is of 1/ 90, and of the homozygote form is 1/ 30000.

The physiopathological expression shows the decrease or absence of the transport of copper in the gall bladder and the consecutive accumulation in the body, mainly in the brain, due to a deficit in ceruloplasmin.

The beginning of Wilson’s disease can take several forms: psychiatric, hepatic, neurological. The disease can manifest itself by cognitive disorders (1), behavioral disorders (2), obsessive-compulsive disorders (3), schizophrenia-like syndrome (4, 5), manic-depressive affective syndrome. In cases where the evolution of the disease is severe, a differential diagnosis with a confusional syndrome (6, 7) or a psychotic disorder is required. The psychiatric symptomatology is polymorphous and it can be masked by the sedative treatment necessary for the improvement of behavioral symptoms. The onset of the disease occurs between the age of 10 and 20, and in rare cases it remains undiagnosed until the age of 40. (8) The first manifestations are hepatic (40%), neurological (35%) or psychiatric (10%), and a more complex form with hematological, renal or combined disorders was described (15%). The most frequent neurological manifestations are: dysarthria, dystonia, rigidity, tremor or dysphagia. (9)

 

Next, we shall present the case of a patient, 23 years old, F, a student, who was hospitalized several times in a psychiatric unit, presenting a symptomatic polymorphism.

 

       The onset of the symptomatology was in 2004 with psychomotor agitation, delirious grandeur ideas, ideas of influence (“I feel manipulated”), mystical ideas (“I am the Holy Spirit”, “I am on a mission to make people better”), ideas of prejudice, poisoning (”something was slipped in my juice when I visited Bran with my parents”), bizarre or addictive behavior (she collected all the icons in the house because they are evil spirits, she asks where to urinate: in bed or in the toilet, she asks permission for anything). A diagnosis of acute psychotic episode was made and she was administered the appropriate treatment. The following hospitalization was in March for psychomotor unrest,  generalized anxiety, depressive mood, insomnia. The treatment included antidepressive, sedative and hypnotic treatment. In June 2007 she was brought in by emergency ambulance, accompanied by her mother for psychomotor agitation, alimentary negative and verbal negativism, rigid posture, attitudinal and movement stereotypes, insomnia, auditory hallucinations, dehydrated teguments. We should mention the fact that, in contrast to the other episodes, the remission of this episode was partial and it required a longer period of hospitalization.  In September 2007 the patient returned to the hospital for the following symptoms: psychomotor unrest, ideative and verbal slowness, hypoprosexia, troubled sleep.  The therapeutic approach was revaluated. The following hospitalization occurred in March 2008 for irritability, irascibility, verbal aggressiveness, clastic crises, insomnia, behavioral disorders. She was diagnosed with bipolar affective disorder, maniac episode with psychotic features, and she followed a treatment with antipsychotics, thymostabilizers, sedatives. We are noticing the fact that the interval between the first and the second hospitalization was of three years, in which time the patient followed a psychiatric treatment for short periods of time. At the beginning of the disease the clinical description included a psychotic aspect, with paranoid features, which later changed to a catatonic form. During the following hospitalization, the symptomatology changed into a depressive affective syndrome. We should mention that during each hospitalization the therapy was adequate, in response to the clinical manifestations. Gradually, during the subsequent hospitalizations, we are noticing an aggravation of the affective disorders (indifference and affective inversion towards the parents) and of the behavioral disorders, irritability, clastic crises, verbal and physical  aggressiveness. The intervals between hospitalizations did not follow a periodicity, the remissions were partial. During the said time the patient continued her university studies with difficulty, she repeated two years of study, and her performances showed a progressive cognitive decline, confirmed by repeated psychological evaluations. In September 2008 the patient came in for hospitalization for psychomotor agitation, irritability, irascibility, verbal aggressivity towards the father, ideas of incurability, of persecution, ideas of helplessness, somatoform disorders. During hospitalization the mood turned from the depressive to the manic state, without any direct relationship with the administered therapy, and depressive or manic ideas were noticed, that were changing from one day to the other.  She comes back for hospitalization in February 2009 for a depressive-anxious clinical description with generalized and paroxistic anxiety,  increased fatigability, decrease of vital force and of pleasure for daily activities, interpretative thoughts, affective flatness. The patient ceased attending university courses, as she could no longer go to the university, she did not have the patience to attend the classes, she could not get out of bed and she could not concentrate. In July 2009 the patient comes back for orofacial dystonia, tremor of the extremities, hypersalivation, tendency of isolation, diminished capacity of affective resonance, sleep disorders, difficulties to concentrate. The family told that she has been taking Leponex 200 mg/day for several months already. On 08.06.2009 the patient accused a stinging sensation in the left eye, and objectively a subconjunctival hemorrhage was diagnosed, for which reason an ophthalmologic examination was recommended, which showed the Kayser-Fleischer ring on both eyes and the suspicion of hepatolenticular degeneration.

 

On the neurological exam: hypertonic-bradykinetic extrapyramidal syndrome

 

Laboratory analyses: HLG 7000 /mm3, PLT 244000/mm3, RBC 5.3 million/mm3, glycemia, creatinine, uric acid, cholesterol, triglycerides, bilirubin, ionogram – normal values. CK 648 U/l       ( 24.07 ), CK 243 U/l ( 03.08 ), CK 1515 U/l ( 10.08 ).

Ceruloplasmin= 0.145g/l ( 0.2-0.4g/dl ), cupremia = 67µg/dl ( 80-155µg), urine cooper = 97.5µg/24h ( 15-70µg/ 24 h ). A treatment of Cuprenil ( D penicillaminum ) 1 cp x 3/day was started.

 

Cerebral MRI showed the following: changes of signal with hyperintense aspect, located at the level of basal ganglia, preponderantly caudate nucleus, some of the thalamic nuclei, extended to the pontomesencephalic tegmentum and to the posterior bulbopontine  region; hyposignal area at the level of the symmetric bilateral putamen; moderate symmetrical enlargement of the intracerebral and pericerebral spaces, as well as of the pericerebellar spaces. The location of the signal changes and their symmetry suggest the diagnosis of degenerative disease with the damaging of the deep grey matter, most probably Wilson’s disease diagnosis.  

 

 

CONCLUSIONS

 

 The psychotic manifestations can occur at the beginning of the disease and they can be interpreted as an acute psychotic disorder.

The polymorphous psychiatric symptomatology included symptoms of the psychotic, manic or depressive, violent behavioral or catatonic syndrome.

        The evolution of the symptoms changed from one day to another, from one week to another, without any correlation with stress factors.

The accidental discovery of a subconjunctival hemorrhage highlighted the clinical and paraclinical signs of Wilson’s disease and the required neurological exam and additional paraclinical investigations led to the introduction of copper chelators in the treatment.

The evolution and the prognosis improved after 4-5 months of specific neurological treatment and they will be monitored in the future.

 

 

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