Hallervorden-Spatz disease now more commonly known as Pantothenate kinase -associated neurodegeneration (PKAN) is a rare autosomal. Pantothenate kinase-associated neurodegeneration (PKAN), also known as neurodegeneration with brain iron accumulation 1 (NBIA1), also called Hallervorden–Spatz syndrome, is a degenerative disease of the. Hallervorden-Spatz syndrome was first described in by Drs. Julius Hallervorden and Hugo Spatz with their study of a family of 12 in which five sisters.
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Pantothenate kinase-associated neurodegeneration PKANformerly called Hallervorden-Spatz syndrome, is a rare, inherited neurological movement disorder characterized by the progressive degeneration of specific regions in the central nervous system neurodegenerative disorder.
Pantothenate kinase-associated neurodegeneration
PKAN is the most common type of neurodegeneration with brain iron accumulation NBIAa group of clinical disorders marked by progressive abnormal involuntary movements, alterations in muscle tone, and postural disturbances extrapyramidal. These disorders show radiographic evidence of iron accumulation in the hallervorden-apatz.
PKAN is inherited halleervorden-spatz an autosomal recessive genetic condition and is described as being classical or atypical. Classic PKAN typically appears in early childhood with symptoms that worsen rapidly. Atypical PKAN, which progresses more slowly, appears later in childhood or early adolescence. Some people have been diagnosed in infancy or adulthood, and some of those affected have characteristics that are between the two categories. Hallervorden-Spatz syndrome was first described in by Drs.
Julius Hallervorden and Hugo Spatz with their study of a family of 12 in which five sisters exhibited progressively increasing dementia and poor articulation and slurred speech dysarthria. The name Hallervorden-Spatz syndrome became discouraged and was replaced hallervorden-satz neurodegeneration with brain iron accumulation because of concerns regarding Dr. Symptoms may vary greatly from case to case. In most cases, progression of the disease extends over several years, leading to death in childhood or early adulthood in classic cases.
Some patients experience rapid deterioration and die within years. Others have a slower progression or can plateau for long periods of time and continue to function into the third decade of life. Atypical individuals often retain a high level of function into later adulthood and some are known to be living in their sixties to seventies.
Symptoms include dystonia, sustained muscle contractions causing repetitive movementsdysarthria abnormal speechmuscular rigidity, poor balance, and spasticity sudden involuntary haolervorden-spatz spasmsThese features can result in clumsiness, gait walking problems, difficulty controlling movement, and speech problems.
Another common feature is degeneration of the retina, resulting in progressive night blindness and loss of peripheral side vision. Dystonia is characterized by involuntary muscle contractions that may force certain body parts into unusual, and sometimes painful, movements and positions. In addition, there may be stiffness in the arms and legs because of continuous resistance to muscle relaxing spasticity and abnormal tightening of the muscles muscular rigidity.
Spasticity and muscle rigidity usually begin in the legs and later develop in the arms. As affected individuals age, they may eventually lose control of voluntary movements. Muscle spasms combined with decreased bone mass can result in bone fractures not caused by trauma or accident. Dystonia affects the muscles in the mouth and throat, which may cause dysarthria and difficulty swallowing dysphagia.
The progression of dystonia in these muscles can result in loss of speech as well as tongue-biting and difficulty with eating. Specific forms of dystonia that may occur in association hal,ervorden-spatz PKAN include blepharospasm and torticollis.
Blepharospasm is a condition in which the muscles of the eyelids do not function properly, resulting in excessive blinking and involuntary closing of the eyelids. Torticollis is a condition in which there are involuntary contractions of neck muscles resulting in abnormal movements and positions of the head and neck.
Many of the delays in development pertain to motor skills movementalthough a small subgroup may have intellectual delays. Although intellectual impairment has often been described as a part of the condition in the past, it is unclear if this is a true feature. Intellectual testing may be hampered by the movement disorder; therefore, hallervprden-spatz methods of studying intelligence are necessary to determine if there are any cognitive features of this condition.
The symptoms and physical findings associated with PKAN gene mutations can be distinguished between classical and atypical disease. Individuals with classical disease have a more rapid progression of symptoms.
In most cases, atypical disease progresses slowly over several years. The symptoms and physical findings vary from case to case. Classical PKAN hallervorden-satz in the first ten years of life average age for developing symptoms is three and a half years. These children may initially be perceived as clumsy and later develop more noticeable problems with walking. Speech delay is also common.
Eventually, falling becomes a frequent feature. Because of the limited ability to protect themselves during falls, children may have repeated injury to the face and chin.
Many individuals with the classic form of PKAN require a wheelchair by their mid-teens in some cases earlier. Individuals with classical PKAN are more likely to have specific eye problems. Approximately two-thirds of these patients will have retinal degeneration. This is a progressive degeneration of the nerve-rich membrane lining the eyes retinaresulting in tunnel vision, night blindness, hallervorden-spztz loss of peripheral vision.
Loss of this peripheral vision may contribute to the more frequent falls and gait disturbances in the early stages. The atypical form of PKAN usually occurs after the age of ten years and progresses more slowly. The average age for developing symptoms is 13 years. Loss of independent ambulation walking often occurs 15 to 40 years after the initial development of symptoms.
The initial presenting symptoms usually involve speech. Common speech problems are repetition of words or phrases palilaliarapid speech tachylaliaand dysarthria. Psychiatric symptoms are more commonly observed and include impulsive behavior, violent outbursts, depression, or a tendency to rapid mood swings. While the movement disorder is a very common feature, it usually develops later. In hallervorden-slatz, atypical disease is less severe and more slowly progressive than early-onset PKAN.
Pantothenate Kinase-Associated Neurodegeneration – NORD (National Organization for Rare Disorders)
In cases of neurodegeneration with brain hallervorden-saptz accumulation Synsrome that are not caused by PKAN, the movement-related symptoms such as dystonia may be very similar. Nine additional genes causing various subtypes of NBIA have been identified at this time. For those without a specific diagnosis or known cause of NBIA, symptoms are more varied because there are probably several different causes of neurodegeneration in this group.
There is a subgroup of patients with moderate to severe intellectual disability. Also, seizure disorders are more common among non-PKAN individuals.
Individuals with PKAN have abnormal accumulation of iron in certain areas of the brain. This is especially seen in regions of the basal ganglia called the globus pallidus and the substantia nigra.
The basal ganglia is a collection of structures deep within the base of the brain that assist in regulating movements.
The exact relationship between iron accumulation and the symptoms of PKAN is not fully understood. This gene encodes the enzyme pantothenate kinase, and mutations in the gene lead to an inborn error of vitamin B5 pantothenate metabolism.
Vitamin B5 is required for the production of coenzyme A in cells. Disruption of this enzyme affects energy and lipid metabolism and may lead to accumulation of potentially harmful compounds in the brain, including iron. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms.
The risk is the same for males and females. All individuals carry abnormal genes. Parents who are close relatives consanguineous have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. PKAN affects males and females in equal numbers.
OMIM Entry – # – NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1; NBIA1
The symptoms typically develop during childhood, although occasionally they begin during late adolescence or adulthood. Cases in infancy and of adult onset have also been reported. The frequency of PKAN is estimated to be one to three per million individuals worldwide.
Because rare disorders like PKAN often go unrecognized, these disorders may be under-diagnosed or misdiagnosed, making it difficult to determine the accuracy of these estimates.
Symptoms of the following disorders can be similar to those of PKAN. Comparisons may be useful for a differential diagnosis. The following three disorders may present with early clinical symptoms that are similar to those seen in classic PKAN:.
Infantile neuroaxonal dystrophy INADalso known as Seitelberger disease, is an extremely rare inherited degenerative disorder of the nervous system characterized by abnormalities of nerve endings axons within the brain and spinal cord central nervous system and outside the central nervous system peripheral nerves. In most cases, infants and children with Seitelberger disease appear to develop normally until approximately 14 to 18 months of age, when they may begin to experience progressively increased difficulties in walking.
In other cases, symptoms may begin at approximately six to eight months of age, at which time infants may experience delays or an arrest in the acquisition of skills requiring the coordination of mental and physical activities delayed psychomotor development.
In some cases, as the disorder progresses, affected children may also experience involuntary movements of the face and hands, sudden involuntary muscle spasms spasticity of the lower arms and legs limbsand progressive paralysis of the legs and lower part of the body paraplegia.
Progressive cognitive failure occurs in association with gradual motor impairment. In most cases, Seitelberger disease is inherited as an autosomal recessive trait. Familial idiopathic basal ganglia calcification FIBGC is a rare neurological disorder characterized by the presence of abnormal calcium deposits calcifications of hallervordne-spatz cause.
Associated symptoms include progressive deterioration of cognitive abilities dementialoss of contact with reality psychosismood swings and loss of acquired motor skills. As the condition progresses, paralysis may develop that is associated with increased muscle stiffness rigidity and restricted movements spastic paralysis.
Additional abnormalities may include relatively slow, involuntary, continual writhing movements athetosis or chorea, a related condition characterized by irregular, rapid, jerky movements. Fucosidosis is a rare genetic disorder characterized by deficiency of the enzyme alpha-L-fucosidase, which is required to break down metabolize certain complex compounds e.
Fucose is a type of the sugar required by the body to perform certain functions essential sugar. The inability to breakdown fucose-containing compounds results in their accumulation in various tissues in the body. Fucosidosis results in progressive neurological deterioration, skin abnormalities, growth retardation, skeletal disease and coarsening of facial features. The symptoms and severity of fucosidosis are highly variable and the disorder represents a disease spectrum in which individuals with mild cases have been known to live into the third or fourth decades.
Individuals with severe cases of fucosidosis can develop life-threatening complications early in childhood. The disease is progressive and, if left untreated, it may cause liver hepatic disease, central nervous system dysfunction, and death. Early diagnosis and treatment may prevent serious long-term disability and life threatening complications.
Treatment is aimed at reducing the amount of copper that has accumulated in the body and maintaining normal copper levels thereafter. Batten disease, a rare genetic disorder, belongs to a group of progressive degenerative neurometabolic disorders known as the neuronal ceroid lipofuscinoses.
These disorders share certain similar symptoms and are distinguished in part by the age at which such symptoms appear. Batten disease is sometimes considered the juvenile form of the neuronal ceroid lipofuscinoses NCLs.