Swiss adults with HFE hemochromatosis, the genetic iron overload disorder, were significantly taller than the average in the country's general population, researchers said, a result perhaps of chronically high levels as children.
Among 176 adult patients with the condition, men were an average of 4.3 cm (1.7") and women 3.3 cm (1.3") taller than the means of 173.9 cm (5' 8.5") and 163.8 cm (5' 4.5"), respectively, overall in Switzerland, according to Pietro E. Cippa, MD, PhD, and Pierre-Alexandre Krayenbuehl, MD, both of University Hospital Zurich.
The increased height in the hemochromatosis patients was significant for both genders (95% CI 3.0-5.5 cm in men, 1.3-5.3 cm in women), the researchers reported in the Aug. 22 issue of the New England Journal of Medicine.
"We speculate that patients with HFE hemochromatosis may benefit in their first 2 decades from constantly enhanced iron absorption, providing a steadily sufficient supply of iron during physical development," they wrote.
Cippa and Krayenbuehl indicated that they thought there might be such an effect after observing that iron deficiency frequently leads to growth retardation. Even in normal children, they noted, "the growth rate affects iron status, and iron demand tends to exceed supply in periods of rapid growth."
Children with chronically high levels of iron, the researchers reasoned, would face such shortages less often, if ever, and may therefore end up taller than average.
The 176 individuals in their cohort all had confirmed iron overload, with serum ferritin levels greater than 300 mcg/L or transferrin saturation exceeding 45%.
All the patients had the so-called C282Y mutation in the HFE gene, with 7% also showing the H63D mutation as well.
Data for average height for the Swiss general population, age- and sex-matched to the hemochromatosis patients, were obtained from the Swiss Federal Statistical Office and military records.
Because HFE mutations are more common in persons of northern European ancestry -- such mutations are believed to have first arisen about 6,000 years ago in Celtic populations, Cippa and Krayenbuehl noted -- they also compared their patients' heights to an Irish reference population.
"The deviation in height from the reference population remained stable over time and did not correlate with the type of HFE mutation, body-mass index, serum ferritin level, liver enzyme elevation, liver fibrosis, or clinical manifestations such as arthropathy or hypogonadism," the researchers wrote.
They suggested, however, that it would be premature to give children iron supplements in the hope of increasing their final adult height.
"Although the first years of life are generally considered vulnerable, it is not clear when and how long iron supplementation might be beneficial," Cippa and Krayenbuehl wrote in an online appendix to their published article. "To our knowledge, the effect of iron supplementation on height in different periods of growth remains to be investigated, and the longest iron supplementation trial lasted 52 weeks."
They noted, too, that iron supplements "are challenged by possible adverse effects."
HFE hematochromatosis is relatively benign, they indicated, because the iron overload "results from a sustained but quantitatively minimal daily increase in intestinal iron absorption from normal food." Clinical iron toxicity is unusual until serum ferritin exceeds 1,000 mcg/L, they added, "a level that is rarely achieved before the age of 20 years."
In contrast, they wrote, a "nonphysiological amount of supplemented iron might lead to oxidative stress and generate free radicals affecting cytokine responses and growth factors, and a high dietary iron amount may inhibit the absorption of other essential nutrients."
The study had no external funding.
Krayenbuehl reported relationships with Shire, Shield Therapeutics, and Vifor Pharma. Cippa declared that he had no relevant financial interests.
- Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
New England Journal of MedicineSource Reference: Cippa P, et al "Increased height in HFE hemochromatosis" New Engl J Med 2013; 369: 785-86.