A patient in their mid-50s with consanguineous parents was seen at our neurological outpatient clinic because of cognitive concerns. The patient had anemia and diabetes. All of the patient’s siblings had diabetes, and a relative with diabetes had speech and walking difficulties. Neurologic examination was normal besides reduced arm swing on both sides. Psychiatric assessment showed a history of depression. Neuropsychologic examination showed no evidence of cognitive deficits. Brain magnetic resonance imaging (MRI) (Figure, A and B) showed extensive symmetrical abnormal susceptibility on T2*-weighted imaging, involving the basal ganglia, thalami, dentate nuclei, and cortex, suspect of neurodegeneration with brain iron accumulation (NBIA). Laboratory test results showed low hemoglobin levels (10.47 g/dL [to convert to grams per liter, multiply by 10]) and elevated hemoglobin A1C levels (8.8% [to convert to proportion of total hemoglobin, multiply by 0.01]). Plasma ferritin level was elevated (530 ng/mL [to convert to picomoles per liquefied natural gas per liter, multiply by 2.247]), with low iron levels (38.55 μg/dL [to convert to micromoles per liter, multiply by 0.179]), low transferrin levels (2.1 ng/mL [to convert to micromoles per liter, multiply by 0.123]), low copper levels (3.82 μg/dL [to convert to micromoles per liter, multiply by 0.157]), and ceruloplasmin levels less than measuring range (<5 mg/dL [to convert to milligrams per liter, multiply by 10]). Liver MRI (Figure, C) showed a high liver iron concentration (1184.36 μg/dL), without signs of iron deposition in the spleen, suggestive of primary hemochromatosis. Ophthalmologic examination was normal. Based on the clinical features and abnormalities on brain MRI, a diagnosis of aceruloplasminemia was suspected. A novel homozygous mutation of the ceruloplasmin gene in exon 6 (c.1192-1196del, p.Leu398Serfs) was found on genetic testing.
Stelten BML, van Ommen W, Keizer K. Neurodegeneration With Brain Iron AccumulationA Novel Mutation in the Ceruloplasmin Gene. JAMA Neurol. Published online October 29, 2018. doi:10.1001/jamaneurol.2018.3230
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