Batten Disease – A Fatal Hereditary Disorder
What is Batten Disease ?
Batten disease is a rare fatal disease of the nervous system disorders that are called neuronal ceroid lipofuscinosis (NCLs). It typically begins in childhood most commonly between ages 5 to 10 years. That is why Batten disease is called a juvenile form of NCLs. (1)
Batten disease is an autosomal recessive disease. It has several forms, but all of them are fatal. The primary reason behind death by Batten disease is due to the accumulation of fatty substances-lipopigments- in cells of CNS, retina, and eye.
Out of every 100,00 babies born in the US, only 2-3 get this disease. It is a genetic disease, so it runs in the family. (2) It may affect more than one person of the same family at the same time. If both parents are a silent career of this disease, they are more likely to transmit it to their kids.
Image 1: Multiple patients of Batten disease in one family
Picture Source: cdn.lifepersona.com
On a cellular level, there are at least 20 genes involved with batten disease buy the most prevalent form of Batten disease is still the juvenile NCL. (3) It is linked with mutations in CLN gene, as proven by a study published in Experimental Neurology Journal. (4)
What causes Batten disease?
It is genetic. The cells contain thousands of genes, which are attached on chromosomes. The human cells have 23 pairs of chromosomes, which make 46 in total. All the genes present on chromosomes control the function of one or more proteins.
These proteins control all the body functions. It includes enzymatic activities inside the body, as enzyme themselves are proteins.
The neuronal ceroid lipofuscinosis is caused by the presence of an abnormal gene, which does not produce their required protein. As a result of which, cells work abnormal, and it leads to developing symptoms of this disease.
Photo 2: A family of healthy and Batten disease affected kids
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Common signs and symptoms of Batten disease
The early signs of Batten disease appear when the baby reaches the toddler age. The symptoms can appear at the age of 2 years. The toddler is more likely to experience vision problems, seizures, and personality changes. He may show mood swings, behavioral changes, slow learning, slow eating, repetitive speech or stumbling.
Over the time, the affected kids get more intense symptoms. They may experience mental impairment, seizures, eyesight loss, motor skills and speech difficulties. (5)
As you have already guessed it by now, Batten disease is a terminal condition where the life expectancy varies by which variation has occurred. Journal of Inherited Metabolic Diseases published research explaining that females with juvenile Batten disease show initial symptoms a year later than male patients. Surprisingly they die a year sooner than male patients, which doesn’t have certain reasons. (6)
Pictures of people suffering from Batten disease
Following are some real pictures showing patients of Batten disease.
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Types of Batten disease
Batten disease is only one form of NCL, but there are many disorders, which refer to the same group of disorders. There are four major types of it, three of which affect children only. All of them cause blindness and are fatal.
It affects babies and makes them have seizures right after birth. The kids affected with congenital NCL have an abnormally small head, which is also called microcephaly. This condition is sporadic and mostly cause death, right after the baby is born.
Infantile NCL shows up when the child reaches the age of 6 months. It may show up till he reaches two years of age. This specific type of Batten disease can also cause microcephaly. It also creates muscular contractions, and patients with infantile NCL don’t live more than five years of age.
Photo 6: A case of juvenile Batten disease
Picture Source: homepages.ihug.co.nz
Late infantile NCL
Late infantile NCL shows up after the age of 2 years. It typically shows symptoms that are not treatable with medicines. Loss of muscle coordination is one of the most common associated sign. Late infantile NCL is fatal, and the patient only lives up to 12 years of age.
Adult NCL can hit a person anytime during adult phase. It starts before the age of 40. The person diagnosed with adult NCL is more likely to have a short lifespan. There is no particular life expectancy of adult NCL. It varies from case to case.
The symptoms of adult NCL are mild as compared to congenital NCL, infantile and late infantile NCL. The progression of the disease is slow. It is the only form of the disease that does NOT cause blindness. (7)
Diagnosis and Tests for Batten disease
Batten disease is misdiagnosed most of the times, which causes increased medical expense and mistreatment. It is not one disease but a set of similar conditions that sometimes confuse diagnosis. All of these conditions show similar symptoms.
Children are the typical victims of juvenile Batten disease. An optometrist or ophthalmologist should initially see any visionary problem in children.
Vision impairment is the first symptom to show up so there are chances that an eye specialist will suspect it. It needs multiple tests to make a final diagnosis of Batten disease. Usually, a neurologist helps you with the required tests. Some of these tests are as follows.
Blood test/urine test
Testing blood and urine helps to detect the abnormalities of Batten disease. In urine, if the levels of dolichol are high, they confirm that individual has Batten disease. Similarly, in blood report, the presence of vacuolated lymphocytes represent that individual is suffering from Batten disease. (8)
Skin sample/tissue sample
Taking a small skin tissue and examining it under the microscope complete this test. In this way, the physician can detect the NCL deposits. The other sites where NCL deposits may appear are muscles, conjunctiva, and rectum.
Image 7: Skin biopsy for diagnosing Batten disease
Picture Source: services.epnet.com
It is a technique that records electrical signals representing specific electrical activity inside the brain. It uses a particular type of probes, which are placed at the suspected person’s scalp. Seizures are best diagnosed with using electroencephalogram.
As vision impairment and loss are typical characters of Batten disease, the eye examination or visual evoked response and electroretinograms are used to detect abnormalities in function.
Photo 8: Ophthalmology based diagnosis of Batten Disease
Picture Source: bdsra.org
Measurement of enzyme activity
In some instances of NCLs, specific enzymes vary or vanish completely. Measuring the levels of these enzymes is also a diagnostic tool for Batten disease.
CT Scan/ MRI test
Both these tests are imaging tests that give an idea to the physician about the visual appearance of the brain. MRI test uses magnetic fields and radio waves to create an image of the brain. Whereas CT scan created a detailed visualization of the brain by using X-rays and attached computers. If any area of the brain is decaying, these tests confirm it. (9)
Image 9: MRI of Brain to diagnose Batten disease
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DNA analysis is a useful diagnostic test for Batten disease. As it is a genetic disease, DNA analysis can detect mutation and the unaffected carriers of this condition. It can be used as a tool for genetic counseling.
Life expectancy of Batten disease patients
Batten disease is a fatal condition that eventually takes the life of its patient. The life expectancy of each form of Batten disease is short. In case of congenital NCL, most of the babies die right after delivery.
The patients of infantile NCL have a life expectancy of maximum 5 years. Late NCL gives only an age of 10 to 12 years of age to its patients. For adult NCL, the life expectancy is variable. (10)
Treatment for Batten disease
There is no as such treatment of Batten disease. It is fatal. The FDA has approved cerliponase alfa as a treatment for only a specific form of Batten disease. It doesn’t work on all types of it. Cerliponase alfa is the only FDA approved treatment which lowers the mobility loss in symptomatic pediatric patients three years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2).
Photo 10: FDA approved first treatment for Batten disease
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The symptoms, i.e., seizures can be improved by taking medicines for seizure. But the actual problem of gene mutation doesn’t have a treatment for it. Some people also use physical or occupational therapy, which improves their function. Scientists are working on it to find a cure for future.