Abstract
BackgroundIn Egypt, Wilson disease seems to be under diagnosed and clinical data on large cohorts are limited. The aim of this study is to highlight the clinical, laboratory and genetic characteristics of this disease in our pediatric population as well as to report our experience with both treatment options and outcome.MethodsThe study included 77 patients from 50 unrelated families (62 were followed up for a mean period of 58.9 ± 6.4 months and 27 were asymptomatic siblings). Data were collected retrospectively by record analysis and patient interviews. Diagnosis was confirmed by sequencing of the ATP7B gene in 64 patientsResultsOur patients had unique characteristics compared to other populations. They had a younger age of onset (median: 10 years), higher prevalence of Kayser-Fleischer rings (97.6% in the symptomatic patients), low ceruloplasmin (93.5%), high rate of parental consanguinity (78.9%) as well as a more severe course. 71.42% of those on long term D-penicillamine improved or were stable during the follow up with severe side effects occurring in only 11.5%. Preemptive treatment with zinc monotherapy was an effective non-toxic alternative to D-penicillamine. Homozygous mutations were found in 85.7%, yet limited by the large number of mutations detected, it was difficult to find genotype-phenotype correlations. Missense mutations were the most common while protein-truncating mutations resulted in a more severe course with higher incidence of acute liver failure and neurological symptoms.ConclusionsEgyptian children with Wilson disease present with early Kayser-Fleischer rings and early onset of liver and neurological disease. The mutational spectrum identified differs from that observed in other countries. The high rate of homozygous mutations (reflecting the high rate of consanguinity) may potentially offer further insights on genotype-phenotype correlation
Highlights
In Egypt, Wilson disease seems to be under diagnosed and clinical data on large cohorts are limited
Initial diagnosis of Wilson’s disease (WD) was made if the patient had hepatic and/or neurologic disease in addition to at least two of the following six criteria[8]: 1- Positive family history of WD 2- Low ceruloplasmin level (< 20 mg%) 3- Presence of Kayser-Fleischer (KF) ring 4- Liver biopsy suggestive of WD (positive staining of copper associated protein, presence of glycogenated nuclei, micro- or macrovesicular steatosis, or ultra structural changes defined by electron microscopy) as measurement of liver copper is not available in Egypt. 5- Elevated baseline 24-hour urinary copper excretion. 6- Coomb’s negative hemolytic anemia
Leipzig score [12] was retrospectively applied to the patients: 73 of them had a score of ≥4 and only 4 children had a score of less than 4; none of whom did mutational analysis at the time of scoring
Summary
In Egypt, Wilson disease seems to be under diagnosed and clinical data on large cohorts are limited. Its frequency increases in populations where consanguinity is more common [1]. It is characterized by decreased biliary copper excretion and defective incorporation of copper into ceruloplasmin, leading to copper accumulation in different tissues mainly the liver, brain and kidneys [2]. WD typically begins with a pre-symptomatic period, during which copper accumulation in the liver causes subclinical hepatitis and progresses to liver cirrhosis and development of neuropsychiatric symptoms. The type of hepatic and neurological symptoms can be highly variable. It may present as fulminant hepatic failure with an associated Coomb’s-negative hemolytic anemia and acute renal failure [3]. If untreated WD causes progressive fatal liver and brain damage [4] and early recognition and treatment is required
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