Neurodegeneration with brain iron accumulation type 4 by mutation in the C19orf12 gene: first time found in adolescent of Russian origin

Background: Neurodegeneration with brain iron accumulation (NBIA) is an autosomal-recessive disorder with a prevalence of approximately 1 to 3:1 million people. In about half of the patients a mutation of the gene coding for the protein pantothenate-kinase (PANK2) is to find (chr. 20p13). Symptoms were progressive movement disorder, dysarthria, dementia, and retinitis pigmentosa. In cMRI a pathognomonic change called eye of the tiger sign could be seen, which corresponds to the brain iron accumulation in the basal ganglia. The absence of the mitochondrial protein C19orf12 causes the clinical subtype 4; this has been previously described in 24 patients of Polish and Turkish origin. The enhanced genetic diagnostics could be performed by means of panel-examination of the genes PANK2, PLA2G6, C19orf12, FTL, FA2 H, ATP13A2, CSF1R, and CP.

Patient: A 14-year-old adolescent with neurodegenerative disease not yet defined with medical history of the family was uneventful. After normal development in early childhood, at the age of 4 years the boy developed clumsiness and a bumpy speech. After school enrollment in the primary school change to a special school at the age of 7 and later to a school for learning and physical disabilities at the age of 11 years. Swallowing was increasingly hindered and photosensitivity was detected. Neurological examination revealed swinging gait, dysarthric speech, reduced muscular strength, pes excavatus and hyperreflexia. In the T2-weighted MRI of the brain the typical eye of the tiger sign was shown. By suspicion of NBIA, genetic analysis of the PANK2 gene with negative result. Panel-diagnostics followed with detection of a 14 bp-deletion in the C19orf12 gene. Hereby, the diagnosis of NBIA type 4 was confirmed.

Conclusion: Despite the negative molecular genetic analysis of the PANK2 gene, but profound clinical and neuroradiological findings, the diagnostic investigation by panel led to the diagnosis of NBIA. Regardless of the patient's origin not only the molecular analysis of PANK2 gene but also the panel-diagnostics should be initiated by suspicion of the disease.