Pantothenate Kinase-Associated Neurodegeneration
Patient Information
Characteristics
Background and History
This is one of a group of disorders resulting from the abnormal accumulation of iron in specific areas of the brain known as the basal ganglia. It has various forms of presentation with early onset and rapid progression in some patients, while others have a later onset and a slower course.
Clinical Correlations
General clumsiness and difficulty walking may be evident in the first decade of life (in a minority of individuals symptoms do not appear until the second or third decade). Tremors, muscle stiffness, and difficulties with fine motor tasks soon become evident. Slurring of speech and swallowing problems are common. Cognitive delays and even mental retardation have been reported. Mental changes such as depression and obsessive-compulsive behavior may be seen. Some patients have movement tics of a repetitive nature. An MRI of the brain can be diagnostic. It is common for patients to become confined to a wheelchair and require supportive care within about 15 years after diagnosis. A significant number of patients have visual difficulties secondary to pigmentary changes in the light- sensing retina.
Genetics
Inheritance
This is an autosomal recessive disorder caused by the presence of two mutations. One is inherited from each carrier parent who is clinically normal. The risk for disease for each child born to such parents is 25%.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
Diagnosis and Prognosis
This is a neurological disorder that is usually diagnosed by neurologists based on the clinical findings and brain changes seen on an MRI. There is no treatment for the disease but individual symptoms may be improved with drugs and deep brain electrical stimulation. These treatments, however, are only sometimes helpful and do not completely alleviate symptoms.
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