Clinical heterogeneity of ATP13A2 linked disease (Kufor-Rakeb) justifies a PARK designation

In this issue of Neurology , Di Fonzo and colleagues describe the identification of a Brazilian patient with juvenile parkinsonism who carries a homozygous missense mutation in ATP13A2 .1 Mutation of this gene has been recently shown to underlie the autosomal recessive, l-dopa–responsive, pallido-pyramidal disease Kufor-Rakeb syndrome (KRS). KRS was originally described by Al Din and colleagues in 1994, when they reported the clinical and radiologic features of five siblings born of a consanguineous marriage and living with their parents in the small homestead of Kufor-Rakeb in Jordan.2 Onset occurred between the ages of 12 and 15 years with lethargy and bradyphrenia evolving over several months culminating in social withdrawal and removal from schooling. Difficulties with walking due to stiffness and postural abnormalities started at around the same time. Within 2 years of onset problems with swallowing and articulating had appeared and assistance was required in several everyday tasks. Cognitive decline continued with slowness of thinking, perseveration, and utilization behavior …