A parkinsonian movement disorder with brain iron deposition and a haemochromatosis mutation.

A 60-year-old, right-handed, Caucasian woman presented to the outpatient department with a three-month history of clumsiness and resting tremor in her right hand, associated with micrographia. She had no significant past medical history. Her family history included a brother who died at the age of 50 after a gastrointestinal bleed, attributed to alcoholic liver disease. Examination showed hypomimia, right hand resting tremor, and right arm and leg rigidity with bradykinesia. There was reduced arm swing during gait, and retropulsion on pull testing. The provisional diagnosis was idiopathic Parkinson’s disease. She was started on dopamine agonists and later on levodopa. However, the symptoms progressed rapidly, with worsening slowness and stiffness, development of postural hypotension and incomplete bladder emptying. She also reported daytime somnolence and snoring at night. As such, the diagnosis was revised to a Parkinson’s-plus syndrome: multiple system atrophy. Investigations revealed mildly raised serum alanine aminotransferase (63 IU/L), but the other liver function tests, full blood count, and copper studies (including serum ceruloplasmin) were all normal. No iron studies were performed. A 24-h cardiac monitor showed no arrhythmias. MRI-head (T1, T2, FLAIR and Gradient echo) at the time of presentation was normal. The patient did not attend for planned autonomic and respiratory function tests. Thirteen months after the first clinic appointment she died in her sleep. A post-mortem examination showed extraand intra-cellular deposition of iron in the globus pallidus, putamen, substantia nigra, locus coeruleus, red nuclei and dentate nuclei. This iron was visualised by Perl’s stain (Figs. 1 and 2), and was in fine granules, in moderate amounts. In addition, there was marked and diffuse neuronal loss from the substantia nigra and locus coeruleus with pale bodies within their neurons. However, no Lewy bodies were seen (alpha-synuclein negative). Axonal spheroids were present, dispersed through brain white matter tracts, consistent with secondary axonal damage. The liver was strongly positive for iron throughout (Perl’s stain). A DNA sample from post-mortem tissue was homozygous for the C282Y Hereditary Haemochromatosis mutation. This is the first case reported of a patient with a movement disorder and a haemochromatosis mutation, in which clear iron deposition in relevant parts of the brain has been seen at postmortem. Several idiopathic neurological conditions (including Parkinson’s disease) are associated with increased brain iron [1], but this is at the level of percentage changes in overall concentration, rather than the gross iron deposition seen in the case reported here. Very high brain iron does occur in conjunction with extrapyramidal disorders in neurodegeneration with brain iron accumulation (NBIA), a group of inherited diseases [2]. Our patient’s age, family history, liver iron, and C282Y mutation all go against this diagnosis. Hereditary haemochromatosis (HH) involves pathological iron deposition in a variety of organs [3]. However, central nervous system disorders are not traditionally listed among the sequelae of the disease. Previous postmortem studies in HH patients have shown excess iron in choroid plexus and pituitary, but not elsewhere in the brain [4], suggesting the blood brain barrier is protective. S. Williams (&) M. R. Vinjam A. Ismail A. Hassan Leeds Teaching Hospitals NHS Trust, Leeds, West Yorkshire, UK e-mail: stefanwilliams@doctors.org.uk