Genetically confirmed Wilson disease in a 9-month old boy with elevations of aminotransferases

Kim, Ju Whi; Kim, Jong Hyun; Seo, Jeong Kee; Ko, Jae Sung; Chang, Ju Young; Yang, Hye Ran; Kang, Kefei

doi:10.4254/wjh.v5.i3.156

Cited by 46 publications

(25 citation statements)

References 11 publications

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“…Examples in the literature support the lack of a well‐described natural history of WD. The earliest symptomatic WD was observed in a 9‐month‐old boy . On the other end of the spectrum, Ala et al .…”

Section: Definition Of the Phenotypementioning

confidence: 98%

Phenotype–genotype correlations in patients with Wilson's disease

Ferenci

2014

Annals of the New York Academy of Sciences

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There is considerable phenotypic variation in Wilson's disease (WD). Some patients present with hepatic disease during the first decade of life and some with neurological degeneration in adolescence or adult life, with or without overt liver disease. Although the absence of neurologic disease in patients with liver disease in childhood or adolescence can be explained by the limited time exposure of the central nervous system to copper toxicity, it is surprising that late-onset neurologic WD can occur without any evidence of liver involvement. This huge variability in the clinical presentation of WD in general reflects our limited knowledge on the natural history of WD. Genetic association studies require the phenotype to be defined as accurately as possible.

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Section: Definition Of the Phenotypementioning

confidence: 98%

Phenotype–genotype correlations in patients with Wilson's disease

Ferenci

2014

Annals of the New York Academy of Sciences

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“…Conversely, WD with onset in early infancy has also been reported, the youngest age of onset being 9 months. 29 However, all children diagnosed in early infancy with genetically confirmed WD presented with hepatic symptoms; it is currently unclear whether WD should also be considered in infants who present with neurological impairment at such a young age. Pediatric neurologists should nevertheless be aware of unusual presentations of WD in childhood such as spasmodic muscle cramps and myopathy.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Wilson's disease and other neurological copper disorders

Bandmann

Weiss

Kaler

2015

The Lancet Neurology

832

534

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Summary The classic copper metabolism disorder, Wilson disease (WD), was first defined in 1912. Both early onset presentations in infancy and late onset manifestations in adults > 70 years are now well recognized. Modern biochemical and genetic prevalence studies suggest that WD may be considerably more common than previously appreciated. Early diagnosis of WD is crucial to ensure that patients can be started on adequate treatment but uncertainty remains about the best possible choice of medication. Direct genetic testing for ATP7B mutations is increasingly available to confirm the clinical diagnosis of WD. WD needs to be differentiated from other conditions that present clinically with hepatolenticular degeneration or share biochemical abnormalities with WD, such as reduced serum cerulo plasmin levels. Disordered copper metabolism is also implied in an increasing number of other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations, and the common late-onset neurodegenerative disorders Alzheimer’s disease and Parkinson’s disease.

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“…Liver manifestations that are related to WD have been reported to first appear in patients aged as young as 9 months and in those aged over 70 years. 11,12 Although the course of the disease tends to be benign if it is diagnosed early, the response to copper chelation or zinc treatment varies and can be accompanied by many sideeffects. 13,14 …”

Section: Clinical Presentation and Treatment Of Wilson Diseasementioning

confidence: 99%

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

Kieffer

Medici

2017

Liver Research

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Environmental factors, including diet, exercise, stress, and toxins, profoundly impact disease phenotypes. This review examines how Wilson disease (WD), an autosomal recessive genetic disorder, is influenced by genetic and environmental inputs. WD is caused by mutations in the copper-transporter gene ATP7B, leading to the accumulation of copper in the liver and brain, resulting in hepatic, neurological, and psychiatric symptoms. These symptoms range in severity and can first appear anytime between early childhood and old age. Over 300 disease-causing mutations in ATP7B have been identified, but attempts to link genotype to the phenotypic presentation have yielded little insight, prompting investigators to identify alternative mechanisms, such as epigenetics, to explain the highly varied clinical presentation. Further, WD is accompanied by structural and functional abnormalities in mitochondria, potentially altering the production of metabolites that are required for epigenetic regulation of gene expression. Notably, environmental exposure affects the regulation of gene expression and mitochondrial function. We present the “multi-hit” hypothesis of WD progression, which posits that the initial hit is an environmental factor that affects fetal gene expression and epigenetic mechanisms and subsequent “hits” are environmental exposures that occur in the offspring after birth. These environmental hits and subsequent changes in epigenetic regulation may impact copper accumulation and ultimately WD phenotype. Lifestyle changes, including diet, increased physical activity, stress reduction, and toxin avoidance, might influence the presentation and course of WD, and therefore may serve as potential adjunctive or replacement therapies.

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Genetically confirmed Wilson disease in a 9-month old boy with elevations of aminotransferases

Cited by 46 publications

References 11 publications

Phenotype–genotype correlations in patients with Wilson's disease

Phenotype–genotype correlations in patients with Wilson's disease

Wilson's disease and other neurological copper disorders

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

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