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Abstract Details

The role of different therapeutic approaches to neurological Wilson´s disease in homozygotic twins with clinical phenotypic variability: case report and literature review
General Neurology
P6 - Poster Session 6 (12:00 PM-1:00 PM)
6-005

Wilson disease is an autosomal-recessive disorder of copper deposition caused by pathogenic variants in the copper-transporting gene, ATP7B.

There is not a clear, strong correlation between genotype and phenotype in Wilson's disease (WD) regarding symptom manifestations. This is supported by the presentation of genetically identical WD-twins with different phenotypic symptoms.
N/A

In one set of female homozygous twins (age: 27yrs), WD was diagnosed by genetic testing. Both were heterozygous for the C.2304dupC;p(Met769Hisf*26) and the C.3207C>A;p(His1069Gln) mutation. One sibling suffered from severe parkinsonian syndrome, anarthria, urinary incontinence, and was wheelchair-bound. However, her sister was married, clinically asymptomatic, and able to help her sister with her daily life. At the time of first visit, the asymptomatic sister was not in therapy; but the severely affected sister was being treated with 350mg D-penicillamine (DPA).

In spite of the immediate increase in dose of DPA (up to 1800 mg within 3 weeks) in the severely affected patient and the initiation of DPA-therapy (up to 600 mg within 3 weeks) in the asymptomatic one, liver function tests deteriorated in both patients (MELD-score of 11 and 6 respectively). During the next 2 months, the parkinsonian patient experienced several falls, broke her right shoulder, and underwent two necessary surgical interventions. Both patients also suffered from severe Vitamin-D deficiency.

During the next 4 months of consequent copper elimination therapy, liver dysfunction improved in both patients. There was even no need for orthotopic liver transplantation (LTX) in the severely affected patient. And her gait, speech, and urinary incontinency started to improve.

Despite identical genetic disposition, WD symptom presentations may develop differently in monozygotic twins, and they may need to be placed in a very different therapeutical regimen. The underlying gene-environment interaction is unclear so far.

Authors/Disclosures

PRESENTER
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