Hereditary Haemochromatosis in Two Cousins with Cluster Headache

Abstract

A 60-year-old woman with secondary chronic cluster headache had increased serum ferritin and serum transferrin saturation and was homozygous for the C282Y mutation in the HFE gene, which is indicative of hereditary haemochromatosis. Treatment with venesection that normalized her iron stores led to a radical improvement of her headache complaints that had been daily for several years. Later, the headache returned to some degree in spite of normal serum ferritin levels. Her cousin, a 33-year-old man who had had episodic cluster headache for several years, also had increased transferrin saturation and was compound heterozygous for two mutations, a genotype known to be associated with a slightly increased frequency of haemochromatosis. This is the first report of a headache disorder in a patient with hereditary haemochromatosis. The coexistence of the two disorders may be a mere coincidence, but the temporary improvement of headache from depletion of iron stores may indicate a causal relation, possibly mediated by iron deposits in pain-modulating centres in the brainstem.

Migraine and erythrocyte biology: a review

“…Stovner et al . described the case of a 60‐year‐old woman with hereditary haemochromatosis and chronic migraine. Therapeutic venesection was started, with removal of 500 mL of venous blood weekly for 2 months.…”

Brain transcriptome perturbations in the transferrin receptor 2 mutant mouse support the case for brain changes in iron loading disorders, including effects relating to long-term depression and long-term potentiation

“…1). In humans, the CACNA1A gene is causatively linked to familial hemiplegic migraine (Ducros et al, 1999;Hans et al, 1999;Pietrobon, 2002) and may provide an intriguing explanation for the increased prevalence of severe headaches reported for people with hemochromatosis or brain iron abnormalities Stovner et al, 2002;Boes et al, 2006;Gaul et al, 2007). (Fig.…”

“…However there have been few, if any, studies of brain iron levels in large cohorts of hemochromatosis patients. While liver damage, arthritis and diabetes are the most well documented clinical consequences of hemochromatosis, some clinical and epidemiological studies have suggested possible associations with neurologic problems, including extreme fatigue (Whitlock et al, 2006;Allen et al, 2008;McLaren et al, 2008) and severe headaches Stovner et al, 2002).…”

Prevalence of HFE (Hemochromatosis) Gene Mutations in Patients With Cluster Headache

“…Migraine and CH may coexist in the same patients and it has been suggested that common genetic factors may play a role in the pathogenesis of both disorders 9 . Finally, a recent report described the coexistence of CH and hemochromatosis in two cousins 10 . Treatment with venesection normalized iron deposits and led to a radical improvement of CH attacks.…”