Cascade screening of familial hypercholesterolemia must go on.

PURPOSE: This study assesses the success of the recently terminated Dutch nationwide cascade screening by examining whether children with familial hypercholesterolemia (FH) were identified through family screening or due to cardiovascular (CVD) events in the FH parent. METHODS: We collected clinical information of all children (0-18 years) with FH with a pathogenic variant at our outpatient lipid clinic between 1992 and 2014 and their FH parents and FH grandparents. RESULTS: We analysed 292 FH children from 205 parents with FH. A history of premature CVD was present in 20% of the parents (29% of the fathers, 9% of the mothers) and 49% of the FH grandparents. CONCLUSION: The fact that CVD is still a presenting event of FH in especially fathers shows that nationwide screening might have been terminated too early. Therefore we recommend to proceed the cascade screening.

Dyslipidemia testing: Why, for whom and when.

Dyslipidemia is a major risk factor for cardiovascular disease. This review addresses why, who and when to test for dyslipidemia. The essence why to test lipids is that those individuals recognized to potentially benefit from primary cardiovascular risk prevention, have a complete cardiovascular risk assessment. Who and when to test lipids differs among the major European, English and American guidelines regarding the recommended age and approach. It is important to note that the threshold and the frequency in whom to perform risk assessment is not established. Most important in decisions concerning lipid testing is communication and to involve individual circumstances.

Predicting non-adherence in patients with familial hypercholesterolemia.

PURPOSE: Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with a high risk of premature coronary heart disease (CHD). CHD prevention consists of lifestyle changes combined with lifelong statin treatment. Good adherence to statins reduces the risk of events substantially. This study was designed to identify determinants of non-adherence and to develop a model predicting non-adherence. METHODS: A single centre survey included all consecutive heterozygous FH patients above age 18 years, who were treated by a specialized team in the outpatient clinic of a university hospital in The Netherlands between 2008 and 2009. In addition to clinical data, patients completed a questionnaire concerning medication adherence. RESULTS: We analyzed 321 patients (169 women) with a statin prescription whose mean age was 46 ± 14 years (± S.D.), and 13 % of the patients had CHD. The untreated mean total cholesterol was 10 ± 2.3 mmol/l. On average, patients were ten years on cholesterol-lowering therapy (range 1-29 years). Adherence was reported by 89 % of the patients (> 90 % adherence). Non-adherence was associated with younger age (OR = 10.64, 95 % CI 2.86-39.68), high total cholesterol level during prescription (OR = 4.29, 95 % CI 1.86-9.89) and a relatively low untreated total cholesterol level (OR = 3.94 95 % CI 1.39-11.14). A prediction model based on these three determinants had a c-index of 0.78 and a calibration with P = 0.88. CONCLUSION: Based on three independent determinants, a prediction model is developed to identify non-adherent FH patients. This model needs to be tested in future prospective research. It might be a first step in improving statin adherence in this extremely high risk group.

[Weight loss, serum sodium concentration and residual symptoms in patients with hypernatremic dehydration caused by insufficient breastfeeding]. / Gewichtsverlies, serumnatriumconcentratie en restverschijnselen bij patiëntjes met hypertone dehydratie door onvoldoende borstvoeding.

OBJECTIVE: To determine the relationship between serum sodium concentration and weight loss as well as residual symptoms in newborns with hypernatremic dehydration caused by insufficient breastfeeding; and to determine the sensitivity of the following rule of thumb 'if weight loss is less than 10%, the baby does not have hypernatremic dehydration caused by insufficient breastfeeding'. DESIGN: Systematic literature search. METHOD: Medline was searched using the terms 'dehydration AND breastfeeding' for case reports on patients with 'hypernatremic dehydration caused by insufficient breastfeeding'. Reference lists from the articles retrieved were also searched. Articles published in 1970-2004 in Dutch, English, French, and German were included. All cases that the author diagnosed as 'hypernatremic dehydration caused by insufficient breastfeeding' were included. RESULTS: A total of 47 articles were found, containing 128 relevant cases. Of these, 9 had less than 10% weight loss. Therefore, the sensitivity of the 10% rule was 93%. We found a linear relationship between the degree of weight loss and serum sodium concentration (Pearson's correlation coefficient = 0.71; p < 0.001). For every 10% increase in weight loss, the serum sodium concentration increased by 16 mmol/l (95% CI: 13-19). As the serum sodium concentration increased, the prevalence of residual symptoms increased. No residual symptoms were reported in patients with less than 10% weight loss. CONCLUSION: A relatively strong linear relationship was found between weight loss and serum sodium concentration. If the weight loss was more than 10%, the serum sodium concentration was beyond the range of normal values. The rule of thumb had a high sensitivity; however, the specificity should be determined before the rule of thumb is implemented.

Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures.

Bethlem myopathy is an early-onset benign autosomal dominant myopathy with contractures caused by mutations in collagen type VI genes. It has been reported that onset occurs in early childhood. We investigated the natural course of Bethlem myopathy in five previously published kindreds and two novel pedigrees, with particular attention to the mode of onset in 23 children and the progression of weakness in 36 adult patients. Our analysis shows that nearly all children exhibit weakness or contractures during the first 2 years of life. Early features include diminished foetal movements, neonatal hypotonia and congenital contractures which are of a dynamic nature during childhood. The course of Bethlem myopathy in adult patients is less benign than previously thought. Due to slow but ongoing progression, more than two-thirds of patients over 50 years of age use a wheelchair.

Genetic localization of Bethlem myopathy.

Bethlem myopathy is a rare autosomal dominant myopathy characterized by slowly progressive limb-girdle muscular atrophy and weakness, and contractures of multiple joints. To identify the genetic localization we used highly polymorphic microsatellite markers in a genome-wide search in six Dutch families. After excluding genetic linkage with 52 markers distributed evenly over the autosomes, significant linkage was present with the 21q22.3 locus PFKL (two-point lod score of Zmax = 6.86 at theta = 0.03). There was no indication of genetic heterogeneity. The pattern of recombinations observed with adjacent markers indicated a localization distal to PFKL. Recombination of a marker within the collagen 6a1 gene (COL6A1) excluded this apparent candidate gene in one of the Bethlem myopathy families. The disease gene is most likely located in the region between COL6A1 and the telomere of chromosome 21q.