Year: 2003
Type: article
Abstract: Two years ago, the report of the European Association for the Study of the Liver (EASL) International Consensus Conference on Haemochromatosis (Adams et al, 2000) concluded: ‘it is estimated that only 5% of C282Y/C282Y men over the age of 40 years will not express an HC (haemochromatosis) [clinical] phenotype’. Such high estimates of clinical penetrance have played a role in the shaping of a positive view regarding the advisability of population screening for haemochromatosis. However, public policy must be based upon rigorously collected and analysed data and not upon clinical impressions. Unfortunately, few data fulfilling these criteria have been available until recently. It is therefore commendable that Deugnier et al (2002) have attempted objectively to compare the symptomatology of homozygous patients against that of wild-type controls (Fig 1). However, their conclusion stating that symptoms are common in the homozygous male (but not female) population is based upon a very small sample, 10 male patients to be exact. Moreover, their conclusions regarding symptoms appear to be based entirely upon the fact that seven of these 10 patients reported fatigue. The responses of white homozygotes for the C282Y mutation and wild-type controls to the questions ‘I believe that I am more tired or have less energy compared to other people my age’ (fatigue) and ‘I currently have severe fatigue, extreme tiredness or exhaustion’ (severe fatigue). The number at the top of each column represents the total number of subjects. Since their paper was submitted, two controlled studies involving much larger samples have been conducted, and it is clear from these studies that symptoms with haemochromatosis are rare, as opposed to common. Following the report of our investigations in the Kaiser Permanente Health Appraisal Clinic earlier this year (Beutler et al, 2002; Waalen et al, 2002), we have added approximately 500 additional subjects to the study before closing patient accrual, bringing the total number examined to 41 613. This group included 56 Caucasian homozygous males who were unaware of the diagnosis of haemochromatosis at the time they completed a relevant questionnaire. There was no significant difference between the responses of the homozygous men to questions regarding fatigue compared with wild-type controls. In a study of 261 homozygous patients detected in a screening programme performed in Norway, Åsberg et al (2002) did not report on ‘fatigue’ as a specific symptom, but did report on the general health of participants: 73·1% of homozygous males and 75% of the wild-type controls considered themselves to be in ‘very good’ or ‘good’ health (A. Åsberg, personal communication). Moreover, in a survey of 2851 patients diagnosed as having haemochromatosis (McDonnell et al, 1999), only 36% of patients complained of extreme fatigue, compared with 30% of the patients who participated in the National Health and Nutrition Examination Survey (NHANES) (McDonnell et al, 1999). In view of the lack of a prominent effect of the C282Y mutation homozygous state on patient fatigue in large studies, we would suggest that the fact that seven of the 10 men questioned in the study by Deugnier et al (2002) complained of fatigue may be due to the type of statistical aberration that is often observed when multiple comparisons of data are made. This is manuscript number 15289-MEM from The Scripps Research Institute. Supported by National Institutes of Health grants DK53505 and RR00833 and the Stein Endowment Fund.
Source: British Journal of Haematology
Authors: Ernest Beutler, Jill Waalen, Vincent Felitti
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2077189337