About santavuori disease
What is santavuori disease?
Santavuori disease, a rare genetic disorder, belongs to a group of progressive degenerative neurometabolic diseases known as the neuronal ceroid lipofuscinoses (NCL). These disorders share certain similar symptoms and are distinguished in part by the age at which such symptoms appear. Santavuori disease is considered the infantile form of the neuronal ceroid lipofuscinoses. The NCLs are characterized by abnormal accumulation of certain fatty, granular substances (i.e., pigmented lipids [lipopigments] ceroid and lipofuscin) within nerve cells (neurons) of the brain as well as other tissues of the body. This may result in the progressive deterioration (atrophy) of certain areas of the brain in addition to neurological impairment and other characteristic symptoms and physical findings.
In most cases, infants with Santavuori disease appear to develop normally until approximately nine to 19 months of age. They may then begin to exhibit a delay in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation). In addition, affected infants begin to lose previously acquired physical and mental abilities (developmental regression). Affected infants may then experience a variety of symptoms including episodes of uncontrolled electrical disturbances in the brain (seizures), impaired ability to coordinate voluntary movements (cerebellar ataxia), abnormally diminished muscle tone (hypotonia), and repeated, brief, shock-like muscle spasms of the arms, legs, or entire body (myoclonic seizures). Affected infants also experience progressive visual impairment due to deterioration of the nerves of the eyes (optic nerves) that transmit impulses from the nerve-rich membranes lining the eyes (retina) to the brain (optic atrophy). Neurological impairment continues to progress and may be characterized by an inability to move voluntarily (immobility); sudden involuntary muscle spasms (spasticity); and lack of response to stimuli in the environment. Life-threatening complications may develop by the end of the first decade. Santavuori disease is inherited as an autosomal recessive trait.
What are the symptoms for santavuori disease?
The signs and symptoms of classic infantile CLN1 disease usually become apparent between 2 and 24 months of age. Infants will develop normally initially, but then become to regress. Their mental and motor development levels off and then begins to decline. Many infants are never able to speak or walk. However, some children do not become ill until later because they still have residual enzyme activity.
Initial symptoms can include signs of intellectual and motor decline including delays in reaching developmental milestones (developmental delays), twItching or jerking of muscles (myoclonic jerks), and seizures. Infants may fail to gain weight and grow as the expected rate (failure to thrive) and may have Diminished muscle tone (hypotonia). They may be restless, irritable and have difficulty sleeping through the night. Some infants exhibit microcephaly, a condition that indicates that a child’s head circumference is smaller than would otherwise be expected based on age and gender. Affected infants and children may also exhibit rhythmic, repetitive, predictable movements of their hands called hand stereotypies.
As children age, the psychomotor abilities (abilities that require coordination of muscular and mental activity) will deteriorate. Infants and children may lose interest in playing. Mild to moderate Intellectual disability may be present. Some children will develop spasticity, where the muscles become tight and stiff and difficult to move and sometimes painful. Progressive Vision loss leading to Blindness can also occur.
In infants and children with the severe form, the disorder is often fatal anywhere between the ages of 2 to 9.
What are the causes for santavuori disease?
Classic infantile CLN1 disease is caused by an alteration in the PPT1 gene (designated CLN1). Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.
The PPT1 gene contains instructions for creating the enzyme palmitoyl-protein thioesterase 1. This enzyme is essential for the proper function of lysosomes. Lysosomes are the primary digestive units within cells. Enzymes within lysosomes break down or “digest” nutrients, such as fats and carbohydrates. In the lysosomal storage disorders, deficiency or improper functioning of particular lysosomal enzymes may lead to an abnormal accumulation of certain complex compounds consisting of fatty materials and/or carbohydrates within the cells of particular tissues of the body. Researchers suspect that classic infantile CLN1 disease is caused by alterations within the cell so that the body is unable to break down and recycle substances such as fats, and their associated sugars and proteins in the normal way in lysosomes. Some of these fats, sugars, and proteins then appear to form the lipopigments that accumulate in nerve and other tissue alongside the symptoms associated with this disorder. Although these substances accumulate in most cells, brain cells are affected first.
The gene alterations that cause classic infantile CLN1 disease are inherited in an autosomal recessive manner. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. 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 inherits 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 for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
What are the treatments for santavuori disease?
The treatment of classic infantile CLN1 disease is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, specialists who diagnose and treat eye disorders (ophthalmologists), specialists who diagnose and treat disorders of the central nervous system (neurologists), speech pathologists, a medical geneticist, a psychiatrist and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Psychosocial support for the entire family is essential as well. Genetic counseling is of benefit for affected individuals and their families.
There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with neuronal ceroid lipofuscinosis.
Some affected infants may require the insertion of a tube through a small opening in the stomach (gastronomy tube) to ensure they receive sufficient food and nutrition.
What are the risk factors for santavuori disease?
Classic infantile CLN1 disease affects males and females in equal numbers. In the United States, classic infantile CLN1 disease along with other forms of neuronal ceroid lipofuscinosis occurs in approximately three in 100,000 live births. Classic infantile CLN1 disease occurs with greater frequency in Finland where its prevalence is estimated to be 1 in 190,000.
Is there a cure/medications for santavuori disease?
Specific therapies for affected infants includes anti-seizure medications called anti-convulsants and medications that relax the muscles to treat spasticity. Specific medications may be used to treat anxiety and sleep disorders. Myoclonus can be treated by medications called diazepines or valproate. Pain medications including opioids and transdermal fentanyl patches have been recommended. Affected children may benefit from occupational, physical, and speech therapy. Additional medical, social, and/or vocation services including special remedial education may be necessary.