Kufor-Rakeb is named for the village in Jordan where it was first described in 1994. In 2010, a mutation in the ATP13A2 gene was deemed responsible. Two U.S. families have been diagnosed with this disorder and there are a few in South America, the Middle East, Asian countries and one from Italy. It has been suggested that only a portion of cases may have iron accumulation; it may develop late in disease course, or it may only be associated with more severe mutations.
Brain CT and MRI may show diffuse moderate cerebral and cerebellar atrophy. Iron accumulation in the basal ganglia affecting the putamen and caudate is present in some, but not all individuals.
Disease onset is usually in adolescence. Presenting symptoms include juvenile parkinsonism, dementia, abnormal eye movements and involuntary jerking of facial and finger muscles. Response to dopaminergic treatment has been noted, followed by the early development of dyskinesias (diminished voluntary movements and the presence of involuntary movements).
Kufor-Rakeb is inherited in an autosomal recessive manner. Because most of our genes exist in pairs (one coming from the mother and one coming from the father), we normally carry two working copies of each gene. When one copy of a recessive gene has a change (mutation) in it, the person should still have normal health. That person is called a carrier.
Recessive diseases only occur when both parents are carriers for the same condition and then pass their changed genes on to their child. Statistically, there is a one in four chance that two carriers would have an affected child. There is a two in four chance the parents will have a child who is also a carrier. The chances are one in four that the child will not have the gene mutation. Carrier testing for at-risk relatives and prenatal testing for pregnancies at risk are suggested if both disease-causing mutations have been identified in an affected family member.
If the disease-causing mutations have been identified in the family, prenatal diagnosis for pregnancies at increased risk can be done. In one test, DNA is extracted from fetal cells obtained by amniocentesis, usually at 15 to 18 weeks’ gestation, and analyzed. Or, sampling is done of the chorionic villus, the tiny finger-like projections on the edge of the placenta, usually at 10 to 12 weeks’ gestation.
Embryo screening, known as preimplantation genetic diagnosis, may be an option for some families in which the disease-causing mutations have been identified.