Idiopathic brain calcification in a patient with hereditary hemochromatosis

Abstract

Background: Detection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported. Case presentation: A 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D-PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative. Conclusions: This report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.

Genetic Risk for Hemochromatosis is Associated with Movement Disorders

“…Although our neuroimaging results are consistent with iron accumulation in associated regions of the brain, lower T2 intensities may also indicate calcification. Indeed a recent case study reported an HH individual who displayed both iron and calcium accumulation for the same brain regions discovered in our analysis 28 . One possible explanation for this observed calcium deposition is that calcium and iron homeostasis are reciprocally connected within these regions.…”

Senile plaque calcification of the lamina circumvoluta medullaris in Alzheimer's disease

“…The case presented here, with both calcified and non‐calcified plaques, cannot be designated as DNTC because plaques, by definition, are absent in the latter. The plaque calcification can, furthermore, not be associated with the knee joint chondrocalcinosis in this case because brain calcification may occur in hemochromatosis but not in chondrocalcinosis 15 . The most probable explanation of the observed calcific deposits is that they are concomitant with the vascular calcification of this region.…”

“…The plaque calcification can, furthermore, not be associated with the knee joint chondrocalcinosis in this case because brain calcification may occur in hemochromatosis but not in chondrocalcinosis. 15 The most probable explanation of the observed calcific deposits is that they are concomitant with the vascular calcification of this region. In a correlative, quantitative study of the human hippocampus in non-Alzheimer subjects, high density areas, as detected on computed tomography, were histologically always validated as calcification of precapillaries, capillaries, and arteries of the molecular and granular layer of the dentate gyrus.…”