Early Onset of Wilson Disease

Abstract

WD can present as early as 2 years of age. Because biochemical tests may be less sensitive in very young children, diagnoses may require a combination of tests. If molecular tests are inconclusive, liver copper content should be measured.

Whole‐exome sequencing identifies novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease phenotype

“…Of 4900 Mendelian disorders, causative genes have been identified for more than 3300. Deleterious genetic variants do not act in isolation, so their clinical manifestations often relate to complex interactions among multiple genes and are additionally affected by environmentally related epigenetic modifications . For this reason, identical manifestations within patients harbouring even the same causal variant are unlikely …”

“…Wilson's disease (WD) is an autosomal recessive metabolic disorder resulting from disease‐causing ATP7B mutations (formally named allelic variants, according to the Human Genome Variation Society) that lead to defective biliary excretion of copper and its accumulation, particularly in the liver and brain . Single‐gene disorders usually manifest in childhood, but the highly variable symptoms of WD develop mostly between ages 5 and 35 years; however, some individuals with these mutations have presented with symptoms as early as 2 years old or have lived into the eighth decade showing no symptoms at all . Early onset of WD occurs with dominant hepatic manifestations (a hepatic phenotype) of any degree of severity, very rarely accompanied by neurologic or psychiatric symptoms (a neurological phenotype).…”

“…[2][3][4][5][6][7][8][9][10] Single-gene disorders usually manifest in childhood, but the highly variable symptoms of WD develop mostly between ages 5 and 35 years; however, some individuals with these mutations have presented with symptoms as early as 2 years old or have lived into the eighth decade showing no symptoms at all. 9,11 Early onset of WD occurs with dominant hepatic manifestations (a hepatic phenotype) of any degree of severity, very rarely accompanied by neurologic or psychiatric symptoms (a neurological phenotype). In turn, neurologic/psychiatric symptoms are common at onset in adults and can be present with liver injury or in isolation.…”

Clinical features and mutational analysis in 114 young children with Wilson disease from South China

“…Early diagnosis, particularly in the presymptomatic period, can greatly improve the prognosis of WD patients. Unfortunately, clinical symptoms during very early childhood are usually mild or atypical (Carlson, Al‐Mateen, & Brewer, ; Eda et al, ; Wiernicka et al, ). The majority of patients with WD develop symptoms between 5 and 35 years of age.…”

Reference intervals of spot urine copper excretion in preschool children and potential application in pre-symptomatic screening of Wilson’s disease

“…With the help of mutation analysis for diagnosis the natural history of WD is changed. More and more young presymptomatic WD patients have been diagnosed before adolescence and treatment can be started early with the potential of preventing significant organ damage and hopefully attaining uneventful life expectancy similar to healthy individuals (6–9). Early and safe treatment of these presymptomatic WD with oral zinc therapy is effective in reducing dietary copper absorption and thus body copper load (6–9).…”