Ann E. Kertesz

Long-Term Survival Analysis in Hereditary Hemochromatosis

This study investigated the long-term survival rates of 85 patients with hereditary hemochromatosis. Eighty-five patients with documented hereditary hemochromatosis diagnosed between 1958 and 1989 and followed up at the University Hospital (University of Western Ontario) medical center were retrospectively reviewed for this analysis. The current status of the patient was assessed by interview or written questionnaire completed by the patient or the family physician. Estimates of differences in survival rates were obtained using Kaplan-Meier life-table and Cox regression analysis. Liver histology, clinical features of the disease, and number of venesections were analyzed to determine their relationship to survival. In the course of a mean follow-up interval of 8.1 +/- 6.8 years (range, 0-31 years), there were 17 deaths among the 85 hemochromatosis patients. Patients with cirrhosis at the time of diagnosis were 5.5 times more likely to die than noncirrhotic patients. Patients who were noncirrhotic at the time of diagnosis had an estimated survival that was not significantly different from age- and sex-matched members of the normal population. Diabetes did not increase the risk of death after data were controlled for the presence of cirrhosis. Early diagnosis and treatment of hemochromatosis in the precirrhotic stage can lead to long-term survival similar to that in the general population. The presence of cirrhosis significantly increases mortality and is the major clinical factor affecting survival.

Screening Blood Donors for Hereditary Hemochromatosis: Decision Analysis Model Based on a 30-Year Database

BACKGROUND & AIMS The high prevalence, morbidity, premature death, and benefit of early diagnosis and treatment make hemochromatosis a prime target for screening in the white population. Decision analysis techniques were used to compare the outcome, utility, and incremental cost savings of a plan to screen voluntary blood donors for hemochromatosis. METHODS The screening strategy includes sequential testing of serum unsaturated iron-binding capacity, serum transferrin saturation, serum ferritin, and either hepatic iron index or venesections to measure exchangeable body iron. Estimates of prevalence, asymptomatic intervals, probabilities of life-threatening clinical complications, symptom-specific life expectancy, and sensitivity and specificity of screening tests are based on our database of 170 hemochromatosis homozygotes and the published literature. RESULTS The screening strategy led to an incremental increase in utility of 0.84 quality-adjusted life days with an incremental cost savings of

Natural history of C282Y homozygotes for hemochromatosis.

3.19 per blood donor screened. When the potential of identifying asymptomatic homozygous siblings was included, these values increased to 1.18 quality-adjusted life days and

Rate of iron reaccumulation following iron depletion in hereditary hemochromatosis. Implications for venesection therapy.

12.57 per person screened. Screening remained a dominant strategy given a prevalence of hemochromatosis of > 0.0026 or an initial screening test cost of <

Abnormalities in iron metabolism in multiple sclerosis.

8. CONCLUSIONS Screening blood donors for hemochromatosis has the potential to improve overall societal health status and decrease third-party payer health care costs over the long-term.

Zinc metabolism in patients on maintenance hemodialysis.

PURPOSE To study the clinical outcomes of subjects who are homozygous for the C282Y mutation of the hemochromatosis gene. SUBJECTS AND METHODS All patients referred to a tertiary referral centre for hemochromatosis were included. The study also included 16 C282Y homozygotes detected in a population screening study. RESULTS The study comprised 277 C282Y homozygotes, including 16 nonexpressing C282Y homozygotes. The mean follow-up period was 7.3 years (range zero to 44 years). The actuarial survival rates of C282Y homozygotes at five, 10 and 20 years were 95%, 93% and 66%, respectively. Life-threatening diseases (cirrhosis, hepatocellular carcinoma, diabetes, heart disease) were present in 36% of male C282Y homozygotes and 19% of female C282Y homozygotes. Cirrhosis of the liver and diabetes were the major clinical symptoms affecting long term survival. Only one nonexpressing homozygote required venesection therapy during the follow-up period. CONCLUSIONS Long term survival is excellent in C282Y homozygotes diagnosed and treated before the development of cirrhosis and diabetes.

Alpha Methyldopahydrazine as an Adjunct to Levodopa Therapy in Parkinson’s Disease

Although venesection therapy is well established for the initial depletion of iron stores in hereditary hemochromatosis, the frequency of subsequent therapy has not been clearly defined. In this study, 21 homozygotes (16 male, five female; mean age of 58, with a range of 26 to 77 years) who had completed initial venesection therapy were followed without further venesections for a mean of 4.0 years (range of 1 to 10.4 years) with iron reaccumulation assessed by annual serum ferritin concentration. Over the follow-up period, the mean rise in serum ferritin was 99 (micrograms/l)/year (range of 1.2 to 241 micrograms/l). The mean interval for the ferritin to become elevated above the normal range in 10 patients was 3.8 years. Eleven of 21 patients required no further venesection therapy over the follow-up interval. There was no significant correlation between the annual rate of ferritin increase and the age or amount of iron removed by prior venesections. These data demonstrate that monitoring body iron stores annually and the selective use of venesections if iron stores reaccumulate is a safe alternative to lifelong venesections every 2-4 months. Many homozygotes will not require reinitiation of venesection therapy for > 4 years. Annual monitoring of body iron stores with reinstitution of weekly venesection when the serum ferritin exceeds the upper limit of normal was a safe alternative to long-term maintenance venesection.

Clinical Presentation of Hemochromatosis: A Changing Scene

High iron concentrations have been reported in the brains of multiple sclerosis victims. To determine if there are abnormalities in general iron metabolism indicative of iron overload in MS, measurements of transferrin saturation, serum ferritin and red cell ferritin in 31 female and 18 male patients were compared to the results in 49 age- and sex-matched healthy controls. Compared to controls, mean serum ferritin in MS was high, whereas transferrin saturation and red cell ferritin were similar. High values in one or more individual test results were observed in eleven MS patients. They were prevalent in patients who required bilateral assistance to walk or were confined to a chair, and appeared to be related to the severity of the disease. An investigation was made into the relationship of the high serum ferritin values in MS to the HLA-A3 histocompatibility antigen, a marker of the hemochromatosis gene which is prevalent in MS. A statistically significant interaction was not found between serum ferritin and the presence of HLA-A3.

Population screening for hemochromatosis: A comparison of unbound iron‐binding capacity, transferrin saturation, and C282Y genotyping in 5,211 voluntary blood donors

Recent studies have focused attention on the possible role of zinc depletion in the pathogenesis of uremic symptoms such as dysgeusia and impotence. The present studies were undertaken to evaluate the prevalence of zinc deficiency and abnormalities of zinc metabolism in patients with end-stage renal disease. A total of 43 stable chronic hemodialysis patients were screened for evidence of zinc deficiency by measurement of fasting predialysis leukocyte and plasma zinc. The results were compared with those from 30 healthy volunteers. Seventeen of these 43 patients had 65Zn absorption measured, and in 9 the rate of disappearance of 65Zn from the body was also measured. The results were compared with those obtained in 20 healthy controls. The nutritional status of these 17 patients was estimated by global nutritional assessment and calculation of the Quetelet index while 9 of 17 had dietary zinc intake calculated from a diet history. The mean plasma zinc level was lower in the hemodialysis patients (11.7 +/- 2.3 mumol/l vs. 13.3 +/- 2.9 mumol/l in controls; p less than 0.05). The mean leukocyte zinc level was 0.81 +/- 0.27 mumol/g dry weight in dialysis patients and 0.81 +/- 0.22 mumol/g in controls (p greater than 0.2). The mean 65Zn absorption in the patients was 49 +/- 14% and in controls 53 +/- 12% (p greater than 0.2). Mean turnover of body 65Zn was 0.47 +/- 0.11%/day in patients and 0.43 +/- 0.18%/day in controls (p greater than 0.1). The mean 65Zn half-life was 154 +/- 29 days in patients and 187 +/- 75 days in controls (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Screening for hemochromatosis in children of homozygotes: Prevalence and cost-effectiveness☆

A double-blind, double-observer study was carried out in twenty-five patients with Parkinsons disease. Alpha methyldopahydrazine in combination with L-dopa was compared to placebo with L-dopa. Combination therapy resulted in a reduction in L-dopa dosage to 1/3 of the amount required during the baseline. There were no side effects attributed directly to the alpha methyldopahydrazine. The overall incidence of side effects in the two groups was similar but the combination therapy significantly reduced the incidence of nausea and vomiting. The limiting factor in the combination therapy was the presence of L-dopa induced dyskinesias.