NCL disease is a rare hereditary disease characterized by nerve cell damage. It occurs due to an abnormal accumulation of material called lipofuscin in the brain. The disease, also called neuronal ceroid lipofuscinosis or cerebellar melting, is generally classified into five different forms: congenital, infantile, late infantile, juvenile and adult forms. It is accompanied by a wide variety of neurological symptoms such as an increase in November, muscle tone, vision problems, speech problems, seizures, dementia, etc. There is no definitive treatment, and the goal of treatment is to control the symptoms.
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What is NCL disease?
What causes NCL disease?
What are the types of NCL disease?
What are the symptoms of NCL disease?
How is NCL disease diagnosed?
How is the treatment of NCL disease performed?
What is NCL disease?
Neuronal ceroid lipofuscinosis (NCL) is the general name of a group of neurodegenerative diseases caused by the accumulation of excessive lipopigment (lipofuscin) in body tissues. Lipopigments consisting of fats and proteins accumulate in the brain and other body tissues and cause symptoms. NCLs are the most common degenerative brain diseases in childhood.
All types of NCL belong to a broader group of diseases known as lysosomal storage disorders, and dementia, epilepsy and motor regression are characteristic for the disease. The characteristics of the symptoms vary, and their onset can occur at any age from birth to young adulthood.
What causes NCL disease?
NCL is a genetic disorder that is inherited from parents. In order for an autosomal recessively transmitted disease to occur in a child, the faulty gene must be obtained from both parents. Only one adult subtype of NCL is transmitted autosomal dominantly, and in this case, a defective gene from a single parent is enough to cause the disease.
In NCL disease, the function of cell organelles called lysosomes is impaired. Lysosomes work like the cell's "recycling bin" and are responsible for breaking down waste, proteins and fat compounds called lipids. Genes that are mutated in NCL disease cannot produce proteins that are necessary for lysosomes to perform their function. These proteins are necessary for the efficient functioning of brain cells (neurons) and other cells. This deficiency in functional proteins results in the accumulation of abnormal materials in lysosomes. A residue called lipofuscin, which is released as a result of the breakdown of lipids in lysosomes, accumulates abnormally in cells and causes damage.
What are the types of NCL disease?
NCL is traditionally classified according to the age of onset of the disease and the form of symptoms. Experts have recently started to classify according to the underlying genetic cause. To date, 14 different gene mutations associated with NCL have been identified. Most forms are inherited in an autosomal recessive manner; however, autosomal dominant inheritance has been reported only in an adult-onset form (neuronal ceroid lipofuscinosis 4B).
NCL disease is classified according to the age of onset as follows:
Congenital NCL
Affected infants have congenital microcephaly, respiratory distress and status epilepticus. Microcephaly is a condition in which the baby's head is noticeably smaller than normal. Status epilepticus is a severe epileptic seizure lasting longer than 30 minutes. Babies born with congenital NCL usually die within the first few weeks of life.
Infantile NCL
Children with infantile NCL disease show normal motor development during the first year. However, after 6 months of age, a slowdown in head growth and November muscle weakness may be detected. Symptoms become apparent after the age of 1 and show rapid progression. It can be confused with Rett syndrome due to aimless repetitive characteristic hand movements. There are seizures of epilepsy, myoclonic jumps, autistic symptoms and loss of eye contact. Developmental skills such as standing, walking and speaking gradually regress. These patients often have seizures by the age of 2 and eventually completely lose their eyesight. They usually lose all their motor abilities and social skills by the age of 2-3, and most of them die before they turn 5 years old.
Late infantile NCL
It typically starts with epilepsy seizures that do not respond to medications between the ages of 2 and 4. Dec. Early signs are loss of November muscle coordination and progressive mental deterioration. Developmental delay begins around the age of 2, and children gradually lose the ability to walk and talk. when they reach the age of 4-5, involuntary myoclonic contractions begin. These patients often die between the ages of 8 and 13.
Juvenile NCL
Juvenile type NCL is also called Batten disease. Its leading symptom is vision loss, which is noticed between the ages of 4 and 7 and usually causes blindness within a few years. Dec. Gradual psychomotor deterioration becomes apparent at the beginning of the school years. The first epileptic seizure occurs on average at the age of 10. In later periods, symptoms such as problems with balance and walking November, muscle stiffness, slouching, speech problems, mental retardation and tremors appear. Aggressive behavior, attention problems, sleep problems and depression are other symptoms that can be seen. Patients become increasingly dependent on their caregivers as they age Decently, and most of them die between the ages of 15 and 30.
Adult type NCL
The adult form of NCL is quite rare and its symptoms usually begin before the age of 40. They are lighter than other forms and progress more slowly. In this form of the disease, vision loss is mild and does not cause blindness.
What are the symptoms of NCL disease?
In almost all forms of NCL, patients are initially healthy and have a normal developmental profile. The main warning sign is the appearance of two or more of the symptoms of dementia, vision loss, epilepsy seizures, and motor impairment. Some of the important symptoms seen in NCL are;
Abnormally increased November muscle tone or spasm
Blindness or vision problems
Dementia
Lack of November coordination
Progressive mental and cognitive impairment
Progressive movement disorder
Aimless repetitive hand movements
Loss of speech
Respiratory distress
Epileptic seizures
Microcephaly: Your head is too small than usual
Walking problems
Posture disorders such as hunching
Children with NCL disease eventually become wheelchair-dependent and bedridden. They lose all their cognitive functions, visual functions and communication abilities. The life expectancy of children with all types of the disease has been significantly shortened. In general, the increase in the risk of premature death depends on the form of the disease and the age of onset.
How is NCL disease diagnosed?
Diagnosis of rare genetic diseases is often difficult. For this reason, even if NCL disease gives symptoms at birth, its diagnosis is usually delayed and it can often be diagnosed in childhood.
Healthcare professionals typically first inquire about the patient's medical history and symptoms for a diagnosis. After a detailed physical examination, various tests and imaging methods are used to confirm the diagnosis. Sometimes accumulations of substances in the eye can be seen during the examination of the bottom of the eye. Deposits accumulate over time and cause a pink and orange circular appearance at the base of the eye. The tests used in the diagnosis include the following:
EEG: Measures the electrical activity in the brain. It is used in the diagnosis of epilepsy seizures.
Electroretinogram: An eye test in which the electrical signals in the retina are evaluated.
Gene test: A blood test performed to investigate whether there are genetic changes in the genes associated with NCL.
Brain MRI or CT scans: Images can show characteristic changes occurring in the brain.
Skin biopsy: Tissue deposits can be detected when examined under a microscope.
How is the treatment of NCL disease performed?
There is no definitive treatment for NCL disorders. Treatment depends on the type and degree of the disease. The goal of treatment is to control the symptoms. Muscle relaxants and antidepressant medications may be prescribed to control irritability, anxiety and sleep disorders observed in the disease. November 19, 2018. Antiepileptic drugs are also used to stop epilepsy seizures. Physical therapy and occupational therapy can help alleviate the symptoms. Specialists are continuing research on the treatment of the disease. Treatments for the disease, such as enzyme replacement, bone marrow or stem cell transplantation, are still under trial.