Families with Wilson's disease in subsequent generations: clinical and genetic analysis.

INTRODUCTION: Wilson's disease is an inherited autosomal recessive disorder of copper metabolism. The prevalence of Wilson's disease in most populations is approximately 1 in 30,000. The risk for offspring is 0.5%. The aim of this study was to establish the frequency of disease among offspring of a cohort of Wilson's disease patients. MATERIALS AND METHODS: In February 2014, our registry included 760 cases of diagnosed Wilson's disease. We selected families in which Wilson's disease was diagnosed in the proband's offspring. RESULTS: Between 1957 and 2014, 1,050 relatives of affected members were screened. Wilson's disease in subsequent generations was observed in nine non-consanguineous families, with 12 affected offspring from nine probands. CONCLUSION: We detected a higher (4.08%) than expected (0.5%) frequency of Wilson's disease among proband offspring, which is in accordance with a recent genetic study in the United Kingdom that suggested a higher WD prevalence in the European population.

Blood vessel ultrastructural picture in a CADASIL patient diagnosed at an advanced age.

We report the case of an 84-year-old male patient afflicted by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) showing minimal symptoms of disease. The patient was diagnosed on the basis of ultrastructural and genetic examinations. Ultrastructurally, a typical vascular pathology was found. However, in abnormal capillary vessel walls no granular osmiophilic material (GOM) was found. In the arteriole there were only a few GOM deposits that revealed various structures, of which only some resembled typical round GOM. The arteriolar walls showed severe damage, including fragmentation, degeneration and loss of vascular smooth muscle cells (VSMCs) with numerous deposits of elastin, mucosubstances, different granular debris, as well as collagen fibres in the basement membrane. Lysosomal inclusions with fingerprint morphology, atypical for CADASIL, were located in some of the VSMCs. Very old age at the onset of the disease may suggest that morphological changes in blood vessels, described in this report, may be due to both the disease and the patient's age. To our best knowledge it is the first description of pathology of blood vessels and GOM morphology in a CADASIL patient diagnosed at an advanced age.