Балалар нейродегенеративтық ауруы: Баттен ауруы

Fatal childhood genetic condition
Although Batten disease is usually regarded as the juvenile form of NCL (or "type 3"), some physicians use the term Batten disease to describe all forms of NCL. Historically, the NCLs were classified by age of disease onset as infantile NCL (INCL), late infantile NCL (LINCL), juvenile NCL (JNCL) or adult NCL (ANCL). At least 20 genes have been identified in association with Batten disease, but juvenile NCL, the most prevalent form of Batten disease, has been linked to mutations in Battenin, the protein encoded by the CLN3 gene. It was first described in 1903. Early signs may be subtle personality and behavioral changes, slow learning or regression, repetitive speech or echolalia, clumsiness or stumbling. Slowing head growth in the infantile form, poor circulation in lower extremities (legs and feet), decreased body fat and muscle mass, curvature of the spine, hyperventilation and/or breath holding spells, teeth grinding and constipation may occur. Over time, affected children experience mental impairment, worsening seizures and progressive loss of sight, speech and motor skills. Batten disease is a terminal disease; life expectancy varies depending on the type or variation. Females with juvenile Batten disease show first symptoms a year later than males, but on average die a year sooner.

NCLs are a family of diseases that are inherited in an autosomal recessive manner. Collectively referred to as Batten disease, NCLs are responsible for most paediatric neurodegenerative diseases. The specific type of NCL is characterized by the age of symptomatic onset and genetic mutation involved. Currently, mutations in ten genes are believed to lead to the development of Batten disease; 'the incidence is as high as one in 12,500 live births'. Late infantile NCL (LINCL): CLN2 encodes for the protein TPP1 which serves as a lysosomal enzyme. Juvenile NCL (JNCL): CLN3 encodes for CLN3, a lysosomal transmembrane protein.

Batten disease is rare; misdiagnosis may lead to increased medical expenses, family stress, and the chance of using incorrect forms of treatment, which may exacerbate the patient's condition. Nevertheless, Batten disease can be diagnosed if properly detected. Vision impairment is the most common observable symptom of the disease. Partial or complete loss of vision often develops in patients who have childhood forms of Batten disease, while it is usually preserved in those with adult onset Batten disease. Children or adults suspected of having Batten disease should initially see an optometrist or ophthalmologist. A fundus eye examination that aids in the detection of common vision impairment abnormalities, such as granularity of the retinal pigment epithelium in the central macula will be performed. Though it is also seen in a variety of other diseases, a loss of ocular cells is a warning sign of Batten disease. If Batten disease is the suspected diagnosis, a variety of tests is conducted to help accurately confirm the diagnosis, including:
Blood or urine tests can help detect abnormalities that may indicate Batten disease. For example, elevated levels of Dolichol in urine have been found in many individuals with NCL. The presence of vacuolated lymphocytes—white blood cells that contain holes or cavities (observed by microscopic analysis of blood smears)—when combined with other findings that indicate NCL, is suggestive for the juvenile form caused by CLN3 mutations. This diagnostic technique is useful, but other invasive tests are more reliable for diagnosing Batten disease. Electroencephalogram (EEG) is a technique that uses special probes attached on to the individual's scalp. It records electrical currents/signals, which allow medical experts to analyze electrical pattern activity in the brain. EEG assists in observing if the patient has seizures. Palliative treatment is symptomatic and supportive. One drug, an antisense oligonucleotide, milasen, described in The New England Journal of Medicine, is believed to be the first "custom" treatment for a genetic disease. It is named after Mila Makovec, the only patient who may ever take it.

Batten disease is named after the British pediatrician Frederick Batten, who first described it in 1903. Also known as Spielmeyer Vogt Sjögren Batten disease, it is the most common form of a group of disorders called neuronal ceroid lipofuscinosis (NCL). Although Batten disease is usually regarded as the juvenile form of NCL, some physicians use the term Batten disease to describe all forms of NCL. Although the trial is not matched, randomized, or blinded and lacked a contemporaneous placebo/sham control group, assessment of the primary outcome variable suggests a slowing of progression of LINCL in the treated children. Researchers believe the neurological deficits common in JNCL could be due to overactive AMPA receptors in the cerebellum. To test this hypothesis, researchers administered AMPA antagonist drugs into affected mice. The motor skills of the affected mice showed significant improvement after the antagonist treatment, which supported the hypothesis that the neurological deficits in JNCL are due to overactive AMPA receptors. This research could eventually help to alleviate neurological deficits of JNCL in humans. In November 2006, after receiving FDA clearance, neurosurgeon Nathan Selden, pediatrician Bob Steiner, and colleagues at Doernbecher Children's Hospital at Oregon Health and Science University began a clinical study in which purified neural stem cells were injected into the brain of Daniel Kerner, a six year old child with Batten disease, who had lost the ability to walk and talk. This patient was the first of six to receive the injection of a stem cell product from StemCells Inc., a Palo Alto biotech company. These are believed to be the first ever transplants of fetal stem cells into the human brain. By early December, the child had recovered well enough to return home, and some signs of speech returning were reported. The main goal of phase I clinical trials, however, was to investigate the safety of transplantation. Overall, the phase I data demonstrated that high doses of human neural stem cells, delivered by a direct transplantation procedure into multiple sites within the brain, followed by 12 months of immunosuppression, were well tolerated by all six patients enrolled in the trial. The patients' medical, neurological, and neuropsychological conditions, following transplantation, appeared consistent with the normal course of the disease. In November 2013, Weill Medical College of Cornell University began recruiting participants for a safety study of a gene transfer vector, described as a non randomised safety and efficacy trial. As part of a trial began by University of Rochester in March 2014. Mycophenolate mofetil is being tested to determine its efficacy and safety using a gene transfer vector. In April 2019, Haney et al. delivered brain soluble lysosomal enzyme TPP1 to treat the disease. Results showed an increased survival rate in late infantile neruonal ceroid lipofuscinosis (LINCL) mice following treatment. Treatment also showed decreased neuroinflammation, a common side effect that leads to neuronal damage and death, compared to that of mice treated with just saline. In complex diseases such as Batten, therapies that address multiple aspects of the disease at the same time have the potential for higher impact than those focusing on one aspect. "The use of several treatment strategies might offer additional benefits to patients with neurodegenerative disease, but the benefits of this approach must be weighed carefully against the additional adverse effects that combined treatments might bring," the researchers wrote. The medical team also noted that "over the past two decades, scientists and clinicians within the Batten disease community have worked to ensure that tools are in place to enable progress towards effective treatments at an unprecedented pace. "Recent progress in Batten disease research offers hope that efficient and targeted therapies will be available soon," the researchers said, noting that "the Batten disease research community is becoming a model of how effective, efficient rare disease research can be accomplished by working together."