From clinical and biochemical to molecular genetic diagnosis of Wilson disease in Latvia.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism characterized by hepatic and/or neurological damage. More than 300 mutations in the gene ATP7B causing this defect have been reported. The data on correlation between WD patient genotypes and clinical presentation are controversial. In this paper the results of ATP7B mutation analysis by testing for mutation H1069Q and direct sequencing of six exons together with the clinical data of 40 Latvian WD patients are presented. Two previously described and two novel mutations as well as one previously reported polymorphism were identified. The H1069Q mutation was present at 52.5% of the disease alleles. One individual among 157 healthy Latvians was also found to be a mutation H1069Q carrier. The estimated incidence of WD in Latvia is approximately 1 in 25600. Wide clinical variability was observed among individuals with the same ATP7B genotype, thus supporting the suggestion that modifying factors play an additional role in the pathogenesis of WD. An algorithm for the diagnosis of WD, including testing for mutation H1069Q, is recommended for the populations where mutation H1069Q accounts for 50% of WD alleles or more.

Study of the etiology and pathogenesis of low grade nonhemolytic unconjugated hyperbilirubinemia (Gilbert's disease).

172 adolescent and adult patients with low grade nonhemolytic unconjugated hyperbilirubinaemia (n.u.h) were examined. Authors have come to the conclusion of the absence of an acquired (posthepatic) form of n.u.h., i.e of the existence of a single --constitutional--form (Gilbert's disease). Viral hepatitis is not likely to play the role of an etiological factor of n.u.h. but of a factor which manifests a congenital defect of bilirubin metabolism. The study of the glucuronidisation found out that its decrease is an important factor in the pathogenesis of the low grade n.u.h. that therefore cannot opposed to the n.u.h. with glucuronyl transferase deficiency group II according to Arias et al. In 61% of patients a moderately shortened erythrocyte life span has been revealed. However the increased bile pigment production in these cases does not speak against Gilbert's disease. The results of biochemical assays have shown that in n.u.h not only the intrahepatic bilirubin metabolism is disturbed but other functions of the liver cell as well. The morphological study of hepatocytes has revealed certain signs of their dystrophy. Based on their investigation the authors propose to single out a group of hereditary pigment hepatoses which include besides Gilbert's disease the syndromes of Crigler-Najjar, Dubin-Johnson and Rotor.