Testing for Haemochromatosis in the Diabetic Clinic

Abstract

SUMMARY.Random serum transferrin saturation (TS) was measured in 1194 patients attending a diabetic clinic. Twenty-one patients had TS> 55070 and in three of these patients repeat random TS was < 55070. Seventeen patients were recalled for fasting serum TS and ferritin measurement. Ten patients had fasting TS> 55%. The diagnosis of haemochromatosis was confirmed by liver biopsy in a total of six patients, three of whom were previously unsuspected. Haemochromatosis was the possible diagnosis in a further four patients. Family studies using HLA typing confirmed haemochromatosis in four family members, three of whom were asymptomatic. We conclude that measurement of TS is a simple and effective method of finding cases of haemochromatosis in the diabetic clinic. Additional key phrases: transferrin saturation; ferritin; liver iron content; serum iron; HLAHereditary haemochromatosis (HH) is an autosomal recessive disorder of iron metabolism." The defective gene lies close to the histocompatibility locus antigen (HLA) on the short arm of chromosome 6.2 Untreated, homozygotes for the disorder absorb excessive amounts of iron which is deposited in various organs and can eventually lead to the clinical signs and symptoms of the disease such as heart failure, cirrhosis, arthritis, pigmentation and diabetes. ' The prevalence of HH may be as high as 4· 5 per 1000,4 one of the commonest autosomal recessive disorders. Not all homozygotes, however, will absorb sufficient iron to become symptomatic. Clinical haemochromatosis develops five times more frequently in men than in women, even though the male: female ratio for homozygosity is the same. It is likely that most cases of haemochromatosis are not diagnosed during life. 5Although HH fulfils the classic criteria of a medical condition suitable for screening, no screening programme exists in the UK and there may be formidable obstacles to the establishment of such a programme in the healthy population."Diabetes is a condition classically associated with HH. In addition to the effect of iron deposition in the pancreatic islet beta cells there may also be a genetic link between the two Correspondence; Dr R M Evans, Biochemistry Department.conditions which would explain the frequent occurrence of diabetes in the siblings of patients with haemochromatosis and diabetes." The diabetes in haemochromatotic patients is similar to other patients with type II diabetes, with normal or exaggerated glucagon response but impaired insulin response to glucose." Depending on the population studied, between 20% and 80% of cases of HH have diabetes rnellitus.P-'? and therefore screening the diabetic population is likely to result in finding new cases of HH. Subsequent investigation of family members of these cases is likely to be successful, because these individuals may be motivated to participate since they have been exposed to morbidity due to the condition in one of their relatives. However, there have been conflicting reports regarding the prevalence of haemochromatosis in diabetics with r...

Population Screening for Haemochromatosis: A Unifying Analysis of Published Intervention Trials

“…I Trials were also excluded if some other screening test (for example, serum iron) was used,":" if diagnostic testing was not routinely available for individuals with positive screening results," " or if the screened population consisted largely of blood donors":" or was not truly population based. [19][20][21][22][23] ·Trial protocol included a third sample with the same criteria for interpretation as sample 2.…”

“…Others focus on screening individuals who are not representative of the general population, such as hospitalised patients, diabetics, or blood donors. [14][15][16][17][18][19][20][21][22][23] Blood donors with the homozygous genotype, by being phlebotomised, are actually receiving treatment for their condition, so it is not surprising that clinical manifestations are less frequent. I 4-18 Intervention trials have used differing cut off levels for the screening tests and often do not account for subjects who fail to complete the diagnostic studies, or subjects homozygous for haemochrornatosis whose measurements fall below the screening cut off level.…”

Re: "Interaction Between Tobacco and Alcohol Consumption and the Risk of Cancers of the Upper Aero-Digestive Tract in Brazil"

“…In a screening study of patients with liver disease, who presumably are more likely to have HHC, the positive predictive value of a single elevated transferrin saturation test was 41 percent (65). In patients with diabetes, the positive predictive value of repeated elevated transferrin saturation tests ranged from 63 to 83 percent when HHC was defined as increased liver iron stores (58,66,67).…”

the screening, diagnosis and optimal management of haemochromatosis

“…The treatment is safe and acceptable and in some countries the blood collected from venesection treatment is utilized by the blood transfusion services. Screening of the general population, 24 particular sub-groups of the population 25,26 and relatives of an index case have been advocated, 1 but so far only the latter is widely accepted.…”

“…40 Although proving statistical signi®cance is dif®cult, there is a de®nite trend to increased haemochromatosis rates in this population with prevalence rates between 1 in 100 and 1 in 200 con®rmed by liver biopsy. 25 Arthralgia is the second commonest feature of haemochromatosis at presentation. 35 One study has examined the prevalence of haemochromatosis in a rheumatology clinic 26 and found the highest prevalence of previously unrecognized haemochromatosis, at 1.5 in 100 cases, of any screened population.…”