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Abstract
Wilson disease (WD) is one of the most common inborn errors of metabolism characterized by degenerative changes in the brain, liver and kidney dysfunction, and Kayser-Fleischer rings due to toxic accumulation of copper. We investigated a Korean family with WD occurred in two consecutive generations. The proband, a 14-yr-old girl, was noticed to have abnormal liver function on a routine health examination at school and was diagnosed of having WD by further laboratory tests and liver biopsy. Molecular genetic analysis of ATP7B gene demonstrated that she was homozygous for Ala-874Val mutation, one of the three common mutations in Korean patients with WD. Further study for her family members revealed that the proband's father, a paternal uncle, and the youngest sister were compound heterozygous for Ala874Val and Asn1270Ser mutations of the ATP7B gene. In addition, the proband's mother and a younger sister were heterozygous carriers of Ala874Val mutation. Therefore, WD occurred in two consecutive generations due to a WD father and a heterozygous mother. Actually, abnormal results on liver function tests were found in the proband's father and a paternal uncle a few years ago but a diagnosis of WD has not been made. Therefore, although WD has been thought to be uncommon in Korea, it should be considered in a differential diagnosis of patients exhibiting abnormal liver function with unknown cause.
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Fig. 1.
Pedigree of the family with Wilson disease. Mutations in the ATP7B gene identified in each family member are indicated. Circle, female; square, male; filled symbol, affected; half-filled symbol, heterozygous carrier; arrow, proband.
Fig. 2.
Result of gene analysis ATP7B. (A) Direct sequencing of exon 11. Arrow shows peak from the nucleotide 2621 position due to heterozygotic or homozygotic C to T transition. (B) Direct sequencing of exon 18. Arrow shows peak from the nucleotide 3809 position due to heterozygotic or homozygotic A to G transition.
Table 1.
Clinical course of Wilson disease and laboratory features at diagnosis
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