Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase.

Neurodegenerative disorders such as Parkinson and Alzheimer disease cause motor and cognitive dysfunction and belong to a heterogeneous group of common and disabling disorders. Although the complex molecular pathophysiology of neurodegeneration is largely unknown, major advances have been achieved by elucidating the genetic defects underlying mendelian forms of these diseases. This has led to the discovery of common pathophysiological pathways such as enhanced oxidative stress, protein misfolding and aggregation and dysfunction of the ubiquitin-proteasome system. Here, we describe loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia (PARK9, Kufor-Rakeb syndrome). Whereas the wild-type protein was located in the lysosome of transiently transfected cells, the unstable truncated mutants were retained in the endoplasmic reticulum and degraded by the proteasome. Our findings link a class of proteins with unknown function and substrate specificity to the protein networks implicated in neurodegeneration and parkinsonism.

Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution.

Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia: Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism, dentatorubral-pallidoluysian atrophy, Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy, Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 gene, and paroxysmal kinesigenic dyskinesia. We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.

Frequency and clinical patterns of multiple sclerosis in Arab countries: a systematic review.

The susceptibility of various populations to multiple sclerosis (MS) and the clinical patterns of the disease are thought to be different. Nineteen articles related to incidence, prevalence and clinical patterns of MS in Arab populations were identified by keyword searching of Medline and Embase, and review of references in all relevant papers. Data were only available for the Kuwaiti, Jordanian, Libyan, Saudi, Iraqi, Palestinian (including Arabs living in Israel), and Omani populations. The publications ranged from 1975 to 2007. In Israel the incidence of MS was 0.7 per 100,000 per year in Arabs born and living in Greater Jerusalem. In Kuwait, the incidence of MS was 2.08 per 100,000. Prevalence varied from 4 to 42 per 100,000 population. The clinical pattern of MS was generally similar to that in western countries. However, one study from Oman found a high rate of optic-spinal disease (affecting one third of patients) and a low rate of oligoclonal bands (OGBs) (only one third of patients); this pattern resembles that of MS described in Asian countries. In conclusion, the prevalence of MS among Arabs has a wide reported range. The clinical pattern is generally similar to "Western type" MS but apparent differences in optic-spinal disease and OGBs positivity need further evaluation. There is significant opportunity for further evaluation of MS in Arabs, especially in unstudied areas, including the populous countries of Egypt, Algeria, Syria, and Morocco. Studies of Arab-Americans and Arab immigrants in Europe could help in defining the effect of immigration on MS. Such studies are likely to enhance our knowledge of the environmental, genetic and clinical variation of MS in Arabs.

Kufor Rakeb disease: autosomal recessive, levodopa-responsive parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia.

Kufor Rakeb disease is an autosomal recessive disorder characterized by subacute, juvenile-onset, levodopa-responsive parkinsonism, pyramidal signs, dementia, and a supranuclear gaze palsy. It was originally described more than a decade ago, and linkage analysis identified a locus on chromosome 1p36 that was previously assigned PARK9. We have further characterized the clinical picture and specifically re-assessed the response to levodopa in the original family, in the northern highlands of Jordan. In the 4 surviving patients, there has been a narrowing of the therapeutic window for levodopa with the emergence of peak-dose dyskinesias with increased spasticity and cognitive decline. Several new features were identified, including facial-faucial-finger mini-myoclonus, visual hallucinations, and oculogyric dystonic spasms.

Corticobasal degeneration syndrome with basal ganglia calcification: Fahr's disease as a corticobasal look-alike?

A 57-year-old man with a 5-year history of progressive left-sided rigidity and apraxia had extensive bilateral calcification of basal ganglia, centrum semiovale, dentate nuclei, and cerebellar white matter on brain imaging. The case is an example of radiological Fahr's disease accompanying a clinical syndrome of corticobasal degeneration. Possible pathogenetic and nosological implications of this association are discussed.