Early Onset of Wilson’s Disease and Possible Role of Disease-Modifying Genes: A Case Report and Literature Review
Wilson’s disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in copper accumulation. Symptoms rarely appear before the age of 5, almost never before 3. The phenotypic variability of WD suggests the presence of modifying factors, making early diagnosis...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Case Reports in Hepatology |
| Online Access: | http://dx.doi.org/10.1155/crhe/3815089 |
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| author | Alessandro La Rosa Angela Elvira Covone Domenico Coviello Serena Arrigo Jacopo Ferro Paolo Gandullia Annalisa Madeo |
| author_facet | Alessandro La Rosa Angela Elvira Covone Domenico Coviello Serena Arrigo Jacopo Ferro Paolo Gandullia Annalisa Madeo |
| author_sort | Alessandro La Rosa |
| collection | DOAJ |
| description | Wilson’s disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in copper accumulation. Symptoms rarely appear before the age of 5, almost never before 3. The phenotypic variability of WD suggests the presence of modifying factors, making early diagnosis challenging. We present a case of symptomatic WD in a toddler, emphasizing the importance of considering WD in differential diagnoses and exploring genetic modifiers influencing disease onset. Clinical and laboratory assessments, including liver biopsy, were performed on a 4.2-year-old boy presenting with hypertransaminasemia and mild hepatomegaly. Histological evaluation revealed chronic hepatitis with fibrosis and severe steatosis, indicating long-standing active disease. Genetic analysis identified a missense variant and a 15-nucleotide deletion in the 5′ UTR promoter region of the ATP7B gene, confirming the WD diagnosis. Additionally, homozygosity for the HFE H63D variant was detected, with transferrin saturations at the upper limit of normal. The patient’s clinical management included a trial of D-penicillamine, discontinued due to side effects, followed by successful zinc acetate therapy. This case underscores the consideration of WD in the differential diagnosis of toddlers. The Ferenci-Leipzig score remains a valid diagnostic tool for WD even in the presence of a single ATP7B variant, although extended genetic analysis should still be considered. Normal ceruloplasmin levels do not rule out WD. Environmental, epigenetic, and genetic factors appear to influence the WD phenotype; HFE variants may act as modifiers given the link between iron and copper homeostasis, possibly explaining the early symptomatic onset in our patient. |
| format | Article |
| id | doaj-art-111d19c2b2724da1a89bba7e11fbbba9 |
| institution | Kabale University |
| issn | 2090-6595 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Hepatology |
| spelling | doaj-art-111d19c2b2724da1a89bba7e11fbbba92024-12-03T00:00:15ZengWileyCase Reports in Hepatology2090-65952024-01-01202410.1155/crhe/3815089Early Onset of Wilson’s Disease and Possible Role of Disease-Modifying Genes: A Case Report and Literature ReviewAlessandro La Rosa0Angela Elvira Covone1Domenico Coviello2Serena Arrigo3Jacopo Ferro4Paolo Gandullia5Annalisa Madeo6Paediatric Gastroenterology and Digestive Endoscopy UnitLaboratory of Human GeneticsLaboratory of Human GeneticsPaediatric Gastroenterology and Digestive Endoscopy UnitDepartment of Laboratory MedicinePaediatric Gastroenterology and Digestive Endoscopy UnitPaediatric Gastroenterology and Digestive Endoscopy UnitWilson’s disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in copper accumulation. Symptoms rarely appear before the age of 5, almost never before 3. The phenotypic variability of WD suggests the presence of modifying factors, making early diagnosis challenging. We present a case of symptomatic WD in a toddler, emphasizing the importance of considering WD in differential diagnoses and exploring genetic modifiers influencing disease onset. Clinical and laboratory assessments, including liver biopsy, were performed on a 4.2-year-old boy presenting with hypertransaminasemia and mild hepatomegaly. Histological evaluation revealed chronic hepatitis with fibrosis and severe steatosis, indicating long-standing active disease. Genetic analysis identified a missense variant and a 15-nucleotide deletion in the 5′ UTR promoter region of the ATP7B gene, confirming the WD diagnosis. Additionally, homozygosity for the HFE H63D variant was detected, with transferrin saturations at the upper limit of normal. The patient’s clinical management included a trial of D-penicillamine, discontinued due to side effects, followed by successful zinc acetate therapy. This case underscores the consideration of WD in the differential diagnosis of toddlers. The Ferenci-Leipzig score remains a valid diagnostic tool for WD even in the presence of a single ATP7B variant, although extended genetic analysis should still be considered. Normal ceruloplasmin levels do not rule out WD. Environmental, epigenetic, and genetic factors appear to influence the WD phenotype; HFE variants may act as modifiers given the link between iron and copper homeostasis, possibly explaining the early symptomatic onset in our patient.http://dx.doi.org/10.1155/crhe/3815089 |
| spellingShingle | Alessandro La Rosa Angela Elvira Covone Domenico Coviello Serena Arrigo Jacopo Ferro Paolo Gandullia Annalisa Madeo Early Onset of Wilson’s Disease and Possible Role of Disease-Modifying Genes: A Case Report and Literature Review Case Reports in Hepatology |
| title | Early Onset of Wilson’s Disease and Possible Role of Disease-Modifying Genes: A Case Report and Literature Review |
| title_full | Early Onset of Wilson’s Disease and Possible Role of Disease-Modifying Genes: A Case Report and Literature Review |
| title_fullStr | Early Onset of Wilson’s Disease and Possible Role of Disease-Modifying Genes: A Case Report and Literature Review |
| title_full_unstemmed | Early Onset of Wilson’s Disease and Possible Role of Disease-Modifying Genes: A Case Report and Literature Review |
| title_short | Early Onset of Wilson’s Disease and Possible Role of Disease-Modifying Genes: A Case Report and Literature Review |
| title_sort | early onset of wilson s disease and possible role of disease modifying genes a case report and literature review |
| url | http://dx.doi.org/10.1155/crhe/3815089 |
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