[Hereditary and acquired transthyretin-mediated amyloidosis]. / Erfelijke en verworven transthyretine-gemedieerde amyloïdose.

We describe three cases, two 70-year-old males with mainly cardiac symptoms and a 34-year-old male with gastro-intestinal and neurologic symptoms. Each patient was shown to have a distinctive type of transthyretin-mediated amyloidosis (ATTR). ATTR amyloidosis is a life-threatening disease characterised by the extracellular deposition of pathogenic transthyretin (TTR). A distinction is made between hereditary ATTR (ATTRv), in case of a pathogenic TTR mutation, and the acquired wild-type ATTR (ATTRwt). The prevalence of ATTR amyloidosis is probably underestimated. The variety of symptoms means that patients often visit several specialists, resulting in an average diagnostic delay of two to three years. Because of the development of new therapeutic possibilities, early diagnosis becomes more important to allow initiation of therapy at an early stage of the disease. Family members should be screened and asymptomatic carriers should undergo follow-up.

Cascade screening for familial hypercholesterolemia: Practical consequences.

Familial Hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the LDLR gene, resulting in elevated serum cholesterol levels and elevated risk of premature cardiovascular disease (CVD). Timely treatment with lipid lowering medication can lower the risk of CVD to the same level of the normal population. Currently the incidence of FH is estimated at 1 in 240 persons in the Caucasian population. A diagnosis of FH can be made on the basis of clinical criteria (including LDL cholesterol and family history) or DNA testing. When a mutation is known within a family an unequivocal diagnosis can be made by DNA testing in family members at any age. Genetic cascade screening is a cost-effective way to identify patients and prevent CVD. Between 1994 until 2014 a nationwide and government subsidized cascade screening program functioned to identify FH patients in the Netherlands. During this time more than 28,000 patients with FH have been identified and entered in a central, national database. Since 2014 cascade screening has been integrated in the regular Dutch health care system. Screening, counseling and treatment are now integrated in the care as a whole of FH patients and families, coordinated by the treating physician, while the national FH database is still maintained. However, since cascade screening by actively approaching family members cannot be applied anymore because of new regulations within the healthcare system, the number of family members participating in the cascade screening program, has plummeted. With this review we would like to highlight the practical consequences of implementing and executing a cascade screening program with a special focus on the lessons learned in the Netherlands.

[A woman with pain, stiffness and skin abnormalities]. / Een vrouw met pijn, stijfheid en huidafwijkingen.

A young woman was diagnosed with SAPHO syndrome. She presented with retrosternal pain and lumbar stiffness in combination with hidradenitis. DXA scan indicated secondary osteoporosis of the lumbar spine caused by chronic inflammation. Bone scintigraphy showed increased sternal uptake. Treatment with immunosuppressive agents was started after which the stiffness improved.