Management of Children and Adolescents with Wilson Disease and Neurological Worsening Following D-Penicillamine Therapy: A Single Centre Experience.

Background: Most centers in developing countries prefer chelation therapy with D-penicillamine for the management of Wilson's disease (WD) because of its easy availability and affordability. Neurological worsening following treatment with D-penicillamine is not uncommon. However, there is a paucity of Indian data on the incidence of neurological worsening in children and adolescents with WD following chelation therapy. Our study objectives were to identify the prevalence of neurological worsening in children and adolescents with WD following chelation with D-penicillamine therapy and to describe the management options and outcomes in these patients. Materials and Methods: In this retrospective chart review, children and adolescents with an established diagnosis of WD from 2010 to 2020 were identified from the hospital electronic database. Among these patients, data of children and adolescents with neurological worsening following D-penicillamine therapy were extracted and analyzed. Results: Neurological worsening was observed in 27/122 (22.1%) children and adolescents with WD on chelation therapy with D-penicillamine. Fifteen patients with neurological worsening following D-penicillamine therapy were managed with zinc monotherapy. Four patients were managed with a combination therapy of zinc and trientine. Five patients were treated with trientine monotherapy. Re-challenging with D-penicillamine at a lower dose followed by a slow dose escalation was attempted in three patients. Gradual clinical and functional status improvement was observed in 24 cases while one patient succumbed to pneumonia. Conclusion: Children and adolescents with WD who had neurological worsening on D-penicillamine therapy may be managed with trientine. Zinc monotherapy with copper restricted diet was also found to be effective in non-affordable patients.

Cri du chat syndrome: a series of five cases.

The cri du chat syndrome (CdCS) is a chromosomal deletion syndrome associated with a partial deletion of the short (p) arm of chromosome 5. We describe five children who were diagnosed to have CdCS by conventional cytogenetic analysis. The deletion was at 5p15 in four patients, whereas the fifth had a larger, more proximal deletion at 5p14. Fluorescence in situ hybridization (FISH) analysis confirmed the deletion of the CdCS critical region at 5p15.2. All five children had global developmental delay and dysmorphism with microcephaly. The other clinical features were variable. Since the clinical diagnosis of CdCS may not always be evident because of the phenotypic heterogeneity, cytogenetic analysis is necessary to establish the diagnosis and confirm that the deletion involves the CdCS critical region. This will enable early intervention which plays an important role in improving the outcome.