Clinical manifestations and BTK gene defect in 4 unrelated Taiwanese families with Bruton’s disease.

Background and objective: X-linked agammaglo-bulinemia (XLA, also called Bruton’s disease) is is an X-linked recessive disorder characterized by recurrent bacterial infections, usually occurring in the first few years of life. Here, we report the results of a BTK gene mutation screening study that was performed in Taiwanese families with the BTK gene defect to further understand the inheritance patterns of XLA patients in Taiwan and to avoid new cases of XLA within families. Materials and methods: In this study, 52 members of 4 unrelated Taiwanese families with the BTK gene defect were enrolled. We studied the immunologic reports of 6 symptomatic living male patients with confirmed BTK gene defects and correlated the findings with their clinical symptoms. The genomic DNA of the subjects was subjected to direct sequencing mutation analysis. Results: We screened 52 members of 4 unrelated Taiwanese families with the BTK gene defect for BTK gene mutation and found that there were 6 symptomatic living patients with a confirmed defect, 7 symptomatic deceased patients highly suspected to have had the defect and 11 asymptomatic female carriers. Conclusions: This is the first report in a series of the thorough screening for the BTK mutation and its carrier status in 4 unrelated Taiwanese families. One pedigree of our study comprises 4 generations. A complete BTK gene mutation study for the patient’s family members is strongly suggested.

A Case of Fabry's Disease with Congenital Agammaglobulinemia

Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the alpha-galactosidase A (GLA) gene, which leads to a GLA deficiency and to the intracellular deposition of globotriaosylceramide (Gb3) within vascular endothelium and other tissues. It manifests as progressive multiple organ dysfunctions caused by the deposition of Gb3. On the other hand, congenital agammaglobulinemia is usually caused by mutations in Bruton's tyrosine kinase (Btk) gene with X-linked dominence, suppresses B cell maturation, and causes recurrent pyogenic infections. In former reports, the distance between the loci in the Xq22 region of the human X chromosome was found to be about 69 kilobases. A 23-yr-old man diagnosed with congenital agammaglobulinemia at age 5, showed typical clinical and laboratory and histopathological findings of Fabry's disease. The genetic basis of this combination of the two syndromes was studied in this patient. Here, we report a case of Fabry's disease with congenital agammaglobulinemia.