Neurodegeneration with brain iron accumulation.
Neurodegeneration with brain iron accumulation (NBIA) describes a group of progressive extrapyramidal disorders with radiographic evidence of focal iron accumulation in the brain, usually in the basal ganglia. Patients previously diagnosed with Hallervorden-Spatz syndrome fall into this category. Mutations in the PANK2 gene account for the majority of NBIA cases and cause an autosomal recessive inborn error of coenzyme A metabolism called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia and pigmentary retinopathy in children or speech and neuropsychiatric disorders in adults. In addition, a specific pattern on brain MRI, called the eye-of-the-tiger sign, is virtually pathognomonic for the disease. Pantothenate kinase is essential to coenzyme A biosynthesis, and the PANK2 protein is targeted to the mitochondria. Hypotheses of PKAN pathogenesis are based on the predictions of tissue-specific coenzyme A deficiency and the accumulation of cysteine-containing substrates. Identification of the major NBIA gene has led to more accurate clinical delineation of the diseases that comprise this group, a molecular diagnostic test for PKAN, and hypotheses for treatment.
Gregory
Allison
A
Department of Molecular and Medical Genetics, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd L103A, Portland, Oregon 97239, USA.
Hayflick
Susan J
SJ
D000818:Animals; D001921:Brain / Q000473:pathology*; D003065:Coenzyme A / Q000378:metabolism; D004195:Disease Models, Animal; D004330:Drosophila; D006801:Humans; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009410:Nerve Degeneration / Q000473:pathology; D006211:Pantothenate Kinase-Associated Neurodegeneration; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics
D007501:Iron; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D003065:Coenzyme A