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 Accumulation: A Novel Mutation in the Ceruloplasmin Gene. JAMA Neurol. 2019;76(2):229–230. doi:10.1001/jamaneurol.2018.3230
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