Fabry's disease is an X-linked metabolic disorder that was initially described in 1898. The incidence of Fabry's disease has been estimated at one per 40,000 to 117,000 worldwide (6
). Deficiency of GLA leads to the storage of neutral glycosphingolipids, particularly of Gb3, in many tissues and cell types. The progressive accumulation of these molecules eventually leads to cellular dysfunction, and possibly to inflammation and/or fibrosis. These processes lead to organ dysfunction and clinical evidence of Fabry's disease. The mechanism of tissue damage is believed to be at least partly due to poor perfusion caused by accumulations in the vascular endothelium, particularly in kidneys, heart, the nervous system, and skin either alone or in combination with deposits in other cell types (2
The progression of clinical symptoms in Fabry's disease can be considered conceptually to follow patient age. Early symptoms in children include acroparesthesia, hypohidrosis, and gastrointestinal symptoms, such as, nausea, abdominal pain, and postprandial diarrhea (7
). However, from age 20 yr, these symptoms tend to progress and proteinuria appear. Renal failure is usually encountered in most men with the disease with concomitant progression in other affected organ systems, which leads to life-threatening cardiac and cerebrovascular manifestations and substantial morbidity (8
The GLA gene, the causative gene of Fabry's disease, is located in the Xq22.1 region. It is about 12 kb long and contains 7 exons that encode a precursor protein of 429 amino acids. The basic molecular defects in Fabry disease include partial deletion, duplication, and point mutation of the GLA gene (9
). Currently, more than 400 mutations have been detected in this gene.
Congenital agammaglobulinemia is a rare humoral immunodeficiency disease. The prevalence of congenital agammaglobulinemia has been estimated at one per 200,000 worldwide (10
). Affected individuals have markedly reduced levels of all major classes of immunoglobulins in serum, and increased susceptibility to recurrent bacterial infections (11
). The most common symptoms of congenital agammaglobulinemia are sinusitis, bronchitis, otitis, and pneumonia, and symptoms usually appear in infancy or early childhood after maternal immunoglobulins have been lost. Approximately 85% of patients with congenital agammaglobulinaemia have the X-linked form due to mutations in the Btk
). The remaining 15% of cases, which clinically are inseparable from X-linked agammaglobulinemia cases, have an autosomal recessive or idiopathic form.
gene, the most common causative gene of congenital agammaglobulinemia, is located in the Xq21.3-q22 region, and was first identified in 1993 (13
). It spans 37.5 kb of genomic DNA, consists of 19 exons (14
), and encodes a 77 kDa cytoplasmic protein tyrosine kinase containing five domains, that is, the N-terminal pleckstrin homology (PH), the proline-rich Tec homology (TH), the Src homology 3 (SH3), the Src homology 2 (SH2), and the catalytic tyrosine kinase (TK) domains (15
). Btk is expressed by all hematopoietic lineages, excepting T lymphocytes and plasma cells, and plays an essential role in the development of B cells. Our ability to identify Btk
gene mutations probably explains why X-linked agammaglobulinemia is the most commonly diagnosed type of congenital agammaglobulinemia, and to date more than 600 unique Btk
gene mutations have been recorded in the BTKbase (a designated international mutation database) (10
The described case had symptoms and signs typical of both Fabry's disease and congenital agammaglobulinemia, respectively. Several disease clusters are located around loci in the Xq22 region, such as, those of Alport syndrome, Fabry's disease, and X-linked agammaglobulinemia. In 1995, Oeltjen et al. (16
) reported that the Btk
gene and the GLA gene are localized in the same 50 to 70 kb region. However, the relationships between genes in this region have not established despite their contiguities. A genetic study was undertaken to detect GLA and Btk
genes abnormalities in present case to investigate whether the co-occurrence of the two syndromes was incidental or inevitable. However, we were unable to find any abnormality in the Btk
gene or any specific genetic relationship between the two disorders, and thus, it appears that their co-occurrence in our patient was coincidental.
Here, we report the first case of Fabry's disease with congenital agammaglobulinemia in 23-yr-old man. Although we were unable to find any abnormality in the Btk gene or any specific genetic relationship between the two disorders, this case provided a rare and interesting opportunity to consider these two syndromes on a genetic basis. It is suggested that more genetic studies should be performed to identify the association between Fabry's disease and congenital agammaglobulinemia.