A disturbed iron metabolism may damage brain and trigger disorders known as neurodegeneration with brain iron accumulation (NBIA). NBIAs are rare, inherited disorders in which responsible mutations affect the function of proteins that participate in tissue iron homeostasis. Accumulated iron, which may be recognized as a low signal intensity on T2-weighted MRI images, oftentimes points to a diagnosis. Recent genetic discoveries confirm that NBIA is not a homogenous group of diseases. Fifteen different NBIAs have been described to date; among these, autosomal recessive inheritance was reported in 13, and autosmal dominant and X-linked dominant inheritance in one disease, respectively. Among NBIAs, the most common is pantothenate kinase-associated neurodegeneration (PKAN-NBIA 1) (30%–50% of all NBIA cases), that occurrs as a consequence of the autosomal recessive mutation in PANK2 gene, followed by phospholipase 2-associated neurodegeneration (PLAN, NBIA 2), due to mutation in PLA2G6 gene, and mitochondrial membrane protein-associated neurodegeneration (MPAN) with the underlying C19orf12 mutation [Table 1]. NBIAs are characterized by complex motor presentations from early-onset degeneration and premature fatality to adult-onset parkinsonism and dystonia. Epileptic seizures, pyramidal signs, visual disorders, and cognitive deterioration can develop. NBIAs are often refractory to therapeutical strategies, although certain interventions may provide significant symptomatic relief in selected patients. In this review, we discuss the expanding clinical spectrum of these complex and rare syndromes, their genetic and imaging features, and potential therapeutical targets and strategies.

Background/Aim. Wilson?s disease (WD) is an autosomal-recessive disorder which is characterized with a marked clinical heterogeneity. The gene responsible for WD is located in 13q14.3 chromosome, contains 21 exons and codes for copper specific transporting P-type adenosinetriphosphatase (ATPase) (ATP7B). Mutations in ATP7B gene change biosynthetic and transporting role of ATPase in cell leading to damaged billiary excretion of copper and its accumulation in the liver, brain, cornea and other tissues. Until now, it has been described more than 400 mutations in ATP7B gene with characteristic geographic distribution. The aim of this study was to assess the spectrum of mutations of ATP7B gene on a large number of patients in Serbian population and to make a correlation between particular genotypes and specific phenotypes. Methods. Eighty-six consecutive patients with WD from WD Clinical Research programme were included in this study. Genetic analysis was performed by direct gene sequencing method. Results. Mutations in ATP7B gene were found in 93% analyzed patients (81.4% of all alleles analyzed). Thirteen mutations were identified, one of which (G998E) was the novel one, so far undescribed in the literature. The most frequent mutation in our population was H1069Q, which was present in 38.4% patients, and the second most frequent mutation was 2304-2305insC (11.6%). Also, a great number of gene polymorphisms of DNA sequences, which do not disturb the ATP7B gene function, was identified. Although neurological form of the disease was more frequent in the group of homozygous for H1069Q and the group of non- H1069Q carriers, there was no statistically significant difference between the groups. Conclusion. Our research showed that genetic diagnosis of WD can be done in 80% of cases by analysis of 5 most common mutations in our population, which facilitate diagnosis significantly. There was no correlation between different genotypes and specific phenotypic features of WD, the presence of psychiatric disturbances and cognitive deterioration.