Family tracing to identify patients with familial hypercholesterolaemia: the second audit of the Department of Health Familial Hypercholesterolaemia Cascade Testing Project.

BACKGROUND: Family tracing is a method recognized to find new patients with familial hypercholesterolaemia (FH). We have implemented family tracing led by FH Nurses and have determined acceptability to patients, feasibility and costs. METHODS: Nurses were located at five National Health Service (NHS) Trusts; they identified FH patients and offered them family tracing. Responses and test results were recorded on a database and summarized on a family pedigree. RESULTS: The majority ( approximately 70%) of index cases participated; the proportion was lower when patients had been discharged from the clinics and in metropolitan areas. On average, 34% (range 13-50%) of relatives lived outside the catchment area of the clinics and could not attend the nurse-led FH clinics. Of the previously untested relatives, 76% who lived in the catchment area of the clinic came forward to be tested. One-third of the relatives who came forward for testing were children

Are patients with familial hypercholesterolaemia well managed in lipid clinics? An audit of eleven clinics from the Department of Health Familial Hypercholesterolaemia Cascade Testing project.

BACKGROUND: Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder which is relatively common, leads to high levels of LDL-cholesterol and if untreated to early coronary heart disease. An audit of current practice at National Health Service Trusts in England was undertaken to determine whether FH patients meet the diagnostic criteria for FH; are being offered appropriate advice and treatment; and to what extent their families are contacted and offered testing for the disorder. METHODS: Medical records of known FH patients (over 18 years of age and diagnosed before 31 December 2003) were accessed to obtain information on diagnosis, treatment and family tracing. RESULTS: The records of 733 FH patients were examined, 79% met the UK 'Simon Broome' register criteria for the diagnosis of definite or possible FH. Analyses showed that patients were usually offered appropriate advice and treatment, with 89% being on a statin. However, the audit indicated a high variability in family tracing between the sites, with significant differences in the frequency of inclusion of a family pedigree in the notes (range 1-71%, mean 35%); the general practitioner (GP) being advised that first-degree relatives should be tested (range 4-52%, mean 27%); and the proportion of relatives contacted and tested (range 6-50%, mean 32%). CONCLUSION: FH patients are well cared for in lipid clinics in England, are being given appropriate lifestyle advice and medication, but an increase in recording of LDL-cholesterol levels may lead to improvements in their management. Practice in family tracing appears to vary widely between clinics.

Targeted screening for genetic haemochromatosis: a combined phenotype/genotype approach.

OBJECTIVE: To evaluate the clinical utility of a targeted screening approach for the detection of genetic haemochromatosis. METHODS: Screening by measuring fasting serum transferrin saturation (TS) and gene testing was carried out in patients in whom a raised serum alanine amino transferase (ALT) activity and raised random serum TS had been found on routine blood testing. RESULTS: During the 29 month study period, 32 patients homozygous for the C282Y genotype were detected from a catchment population of 330,000 by screening blood samples referred initially for routine laboratory liver function tests. By comparison, during the same period of time and within the same population, only seven patients were found by clinical suspicion alone. The patients in the study, after treatment by venesection, have shown both clinical and biochemical improvement. CONCLUSIONS: The study shows that from a population of patients in whom a routine liver function profile had been requested, it is possible to detect subjects homozygous for the C282Y HFE genotype who have clinical or biochemical markers of iron overload.

Quarts out of pint pots -- expanding the pint. Clinical budgeting in practice.

Clinical budgeting is the process whereby clinical users are charged for the resources they use. A system for recharging users for the costs of tests was introduced at the Northern General Hospital, Sheffield, in 1995, and has been in operation since. The system has allowed pathology to maintain budgetary balance, has automatically compensated for workload increases, has allowed the introduction of new tests, and has encouraged clinical users to include pathology costs in their bids for funding for clinical developments. The system works according to rules agreed between pathology and its users at the outset, but once set up takes a minimal amount of work to operate and maintain.

Screening for genetic haemochromatosis in blood samples with raised alanine aminotransferase.

BACKGROUND: In the UK approximately 1 in 140 people are homozygous for the C282Y mutation of the HFE gene and are at risk from iron overload caused by genetic haemochromatosis (GH). Early detection can prevent organ damage secondary to iron deposition and increase life expectancy. AIM: To screen for GH in all blood samples sent to the laboratory for routine liver function tests in which raised serum alanine aminotransferase (ALT) activity was detected. METHODS: ALT was measured in sera sent to the laboratory for routine liver function tests. In those samples found to have raised activity, transferrin saturation and ferritin were measured followed by genetic testing when transferrin saturation was increased. RESULTS: Of the 35 069 serum samples assayed for routine liver function tests, 1490 (4.2%) had raised ALT levels (>50 u/l). Transferrin saturation and serum ferritin concentrations were measured in these patient samples, and in 56 transferrin saturation was >60%. Further blood samples were requested from these patients for genetic testing: 33 samples were obtained. There were nine patients homozygous for the C282Y mutation of the HFE gene and three compound heterozygotes (heterozygous for both C282Y and H63D mutations). CONCLUSIONS: The association of raised ALT activity and transferrin saturation of >60% could provide a simple, cost effective method for detecting individuals with clinical haemochromatosis. Although many patients with GH may have been missed, this study suggests that the clinical penetrance of the disorder may be much lower than is generally supposed and that genetic screening will identify many people who may never develop clinical haemochromatosis.

Serum fructosamine does reflect levels of glycated serum albumin in insulin-dependent diabetics.

Fructosamine was measured in the serum of 62 patients with insulin-dependent diabetes (IDD) and 32 non-diabetics and the results compared with glycated albumin levels (GSA) measured using the affinity medium Cibarcron blue F3GA. Good correlations were found both for the IDD patients (r = 0.93) and the combined group of IDD plus non-diabetics (r = 0.95). We conclude, that fructosamine measurements accurately reflect GSA concentrations, and, therefore, provide a practical method for assessing intermediate term glycaemia in IDD.

Comparison of serum fructosamine with glycosylated serum protein (determined by affinity chromatography) for the assessment of diabetic control.

Glycosylated total protein (GTP) and glycosylated albumin (GALb) were measured in serum using aminophenylboronic acid affinity chromatography and the results were compared with those found using the fructosamine assay. The percentage GTP and GALb found by affinity chromatography correlated well with fructosamine values in the sera of a group of non-diabetic and diabetic patients (fructosamine vs GTP, r = 0.91, p less than 0.001; fructosamine vs GALb, r = 0.91, p less than 0.001). Results of each method gave similar correlations when compared with the degree of diabetic control assessed by glycosylated haemoglobin (GHb) and fasting plasma glucose (FPG) (fructosamine vs FPG, r = 0.74, p less than 0.001; GTP vs FPG, r = 0.75, p less than 0.001; GALb vs FPG, r = 0.79, p less than 0.001; fructosamine vs GHb, r = 0.79, p less than 0.001; GTP vs GHb, r = 0.81, p less than 0.001; GALb vs GHb, r = 0.84, p less than 0.001). Both methods could equally discriminate between groups of non-diabetics and diabetic patients (p less than 0.001) and showed similar temporal changes after starting insulin therapy.

Simple colorimetry of glycated serum protein in a centrifugal analyzer.

A recently described (Clin Chim Acta 127: 87-95, 1982) colorimetric assay for glycated proteins in serum exploits their ketoamine activity to reduce 3,3'-(3,3'-dimethoxy-4,4'-biphenylylene)bis [2-(p-nitrophenyl)-5-phenyl-2H-tetrazolium chloride] (nitroblue tetrazolium) in alkaline solution; the authors termed this the "fructosamine assay." The method is simple, requiring only the addition of one reagent and measurement of the absorbance change during 5 min; results are expressed relative to a synthetic standard. We have adapted this for use in a centrifugal analyzer and report its performance, both analytically and as an index of hyperglycemia. Precision is good (between-batch CV 2.1%), the reagent is stable and inexpensive, and the procedure is rapid (75 samples per hour). Albumin influences the measurement, but for concentrations greater than or equal to 35 g/L this was not a serious problem. Normal and diabetic populations can be clearly discriminated (p less than 0.001). The test detected 25 (84%) of the 30 untreated diabetics studied and gave four false positives (8%). The results correlate well with those for glucose in plasma of fasting subjects (r = 0.87) and for hemoglobin A1 (r = 0.80).