NCL stands for Neuronal ceroid lipofuscinosis. The term neuronal ceroid lipofuscinosis describes various forms of a hereditary and hitherto incurable metabolic disease of the central nervous system and the retina. What all ten forms of the disease have in common is that ceroid, a waxy metabolite, and lipofuscin, which contains fat and protein, are deposited in the nerve cells and result in a gradual loss of function. Certain forms of the disease already appear in infancy or childhood and lead to a complete loss of cognitive and motor skills via gradual blindness, epilepsy and dementia.
What is neuronal ceroid lipofuscinosis?
Ten different variants of the hitherto incurable hereditary disease neuronal ceroid lipofuscinosis (NCL, also CLN) are known, some of which already break out in infancy and early childhood, others only in adulthood. All forms of the disease are characterized by typical ceroid and lipofuscin deposits in the nerve cells and in the retina. See AbbreviationFinder for abbreviations related to NCL.
Ceroid is a wax-like substance and lipofuscin is a brownish substance containing protein and fat. Both are intermediate waste products of cell metabolism that are normally further processed or transported away and excreted. The deposits in the nerve cells and in the cells of the retina cause a gradual loss of function, which initially manifests itself in a reduction in vision and brain performance in the cognitive and motor areas.
The different forms of NCL are named NCL1 to NCL10 in the order in which they were discovered. While the occurrence of most forms of the disease is limited to a typical age, a few forms, such as CLN1, can occur in late infancy or even in adulthood.
In addition to the typification and designation of neuronal ceroid lipofuscinosis as NCL1 to NCL10, verbal designations are also common, which either point to their discoverer or to the respective age, such as infantile, juvenile or adult NCL.
Only gene mutations can be considered as the cause of the various forms of neuronal ceroid lipofuscinosis. The loci of the mutated genes that are ‘responsible’ for triggering each and every manifestation of the disease are not all on the same chromosome but affect several different chromosomes. This means that the metabolic processes involved are complex and multi-stage conversions, of which each individual stage can be disrupted and lead to similar symptoms.
With the exception of NCL4 (adult NCL), which is inherited in an autosomal dominant manner, all other forms of the disease are inherited in an autosomal recessive manner. This means that no form of the disease involves the X or Y sex chromosomes and that both partners must have the same mutational allele of the gene in question for the disease to occur. Only in the case of NCL4 is it sufficient for the disease to break out if either the man or the woman has the mutated gene (autosomal dominant inheritance).
Symptoms, Ailments & Signs
The symptoms of all ten known forms of neuronal ceroid lipofuscinosis take place in a similar form and sequence. Increasing visual impairment with deposits of ceroid and lipofuscin in the retina cells characterize the first symptoms and signs of the disease. The visual impairment progresses progressively and, for example in juvenile NCL, leads to complete blindness after one to two years.
At the same time, those affected show cognitive and motor impairments, which worsen as the disease progresses and can trigger hallucinations and epileptic seizures. The disease is always accompanied by dementia, even in the case of affected babies or small children. All signs and symptoms increase over a time frame of about 10 to 15 years as the disease progresses, ultimately leading to death because there is as yet no cure for the disease.
Diagnosis & course of disease
The final determination of the presence of a form of neuronal ceroid lipofuscinosis is always accompanied by a very poor prognosis, so that the diagnosis should be appropriately secured. Different examinations are possible for the different forms of NLC.
If a first suspicion arises due to non-specific symptoms such as declining vision, dementia and epileptic seizures and if NCL diseases become known within the family, the suspicion should be backed up by a clear diagnosis or rejected. An eye examination of the retina for fuscin and ceroid deposits provides reliable information. Tissue samples can also be taken, which can be examined microscopically for deposits.
The activity of certain lysosomal enzymes provides further important information. In the presence of NLC10, the congenital form of NLC, which is already active from birth, a reduced activity of cathepsin D is a reliable indicator of NLC10 disease. Magnetic resonance tomography is the main imaging method available, with which, for example, the degradation of brain substance can be clearly identified. Ultimately, examining certain genes for the presence of the mutations that cause the disease provides a final certainty.
Patients with this disease can suffer from various symptoms and limitations. For this reason, a general course cannot usually be predicted. However, this leads to limitations in the motor and cognitive abilities of those affected, so that the patients are significantly restricted in their everyday life and in many cases also depend on the help of other people.
Most of those affected suffer from poor eyesight, which increases as the disease progresses. In the worst case, this can lead to complete blindness. Children and young people in particular can suffer from severe mental health problems or depression as a result of blindness. Epileptic seizures also occur with this disease and reduce the quality of life. In the worst case, this can lead to the death of the person concerned.
Most patients also suffer from dementia and hallucinations. The life expectancy of those affected is significantly reduced by the disease. Unfortunately, the disease cannot be treated. The individual symptoms can be alleviated. However, the disease is not completely cured.
When should you go to the doctor?
If epileptic seizures, visual disturbances and other classic signs of neuronal ceroid lipofuscinosis are noticed, a doctor’s visit is recommended. The rare brain degradation diseases progress rapidly and require early clarification by the doctor. People who suffer from the above symptoms without any other cause are best advised to make an appointment with a neurologist. He can narrow down the possible suffering and make a diagnosis based on various physical examinations.
Since neuronal ceroid lipofuscinoses are hereditary, a diagnosis may be possible before birth, provided there is a relevant family history. The disease can be recognized at the latest during the newborn screening. If this is not the case, the parents must consult the doctor if the symptoms mentioned above appear. In addition to the family doctor and neurologist, various specialists such as the ophthalmologist or an orthopedist can be involved in the treatment. A physiotherapist must also be consulted. Neuronal ceroid lipofuscinoses are chronic and therefore always require close medical monitoring.
Treatment & Therapy
So far, no therapies are known that lead to a cure of any form of NLC. This means that mainly treatments that alleviate individual symptoms as well as possible come into question. In addition, palliative measures become more important in the advanced stage of the disease.
In the case of juvenile and late juvenile forms of NLC, which are not readily recognized in the early years due to normal child development, psychotherapeutic treatment is also important because the children and adolescents become aware of the loss of their cognitive and motor skills.
Outlook & Forecast
The prognosis of neuronal ceroid lipofuscinosis is unfavorable. The disease is characterized by a progressive disease course. The causative disorder can be found in a mutation in human genetics. Current legislation prohibits scientists and researchers from using treatments that involve altering human genetics.
Therefore, the treating physicians focus on an early diagnosis and the use of treatment measures that lead to the containment of the progression of the disease. In addition, any symptoms that occur should be alleviated as best as possible in order to improve the quality of life. A cure for any of the known forms of the disease is currently impossible.
Those affected show symptoms of different severity. The patients depend on daily help and support in everyday life, since they cannot cope with the tasks that arise on their own. The disease is accompanied by serious disorders that settle in the motor and mental area. In addition, irregularities and impairments of sensory perception are to be expected. Blindness often occurs.
Ultimately, the disease is associated with a reduction in average life expectancy. Due to this difficult course of the disease, the patient and his relatives are in a state of strong emotional stress. The risk of the additional outbreak of a mental disorder is therefore increased.
Preventative measures that could prevent or delay the outbreak of NLC are not (yet) known. If the disease occurs within the family, genetic tests should also be carried out on healthy family members is ultimately left to each individual after careful consideration.
There are several forms of neuronal ceroid lipofuscinosis. They differ in terms of their course and prognosis. So far, no variant of neuronal ceroid lipofuscinosis can be cured. Therefore, aftercare in the actual sense is usually not necessary and possible. In most cases, the affected children need to be closely monitored throughout their lives.
Depending on the form of the disease and the chosen therapeutic approach, various follow-up and control measures are necessary. In some variants of neuronal ceroid lipofuscinosis, those affected die a few hours or days after birth. They are usually cared for in the neonatal intensive care unit until their death.
Affected parents can, if necessary, take advantage of psychotherapeutic help as part of aftercare. Since neuronal ceroid lipofuscinosis is a hereditary disease, you should consult a genetic counseling center. This is particularly advisable if you are planning to have children.
There is often a risk that future children will be affected by the disease. A few forms of neuronal ceroid lipofuscinosis can be treated with medication. Strict medical control is necessary in these cases. In addition, there are experimental procedures that should lead to a complete cure. Due to its novelty, however, no statements can be made about future follow-up care.
You can do that yourself
Neuronal ceroid lipofuscinosis is basically incurable. However, this does not mean that there are no opportunities to cope well with everyday life with the disease.
First, it should be ensured that available drug therapies are used. By taking medication regularly, symptoms such as seizures or spasticity can be avoided or at least reduced. Feeding through a tube is often helpful. It is advisable to find out about the advantages and disadvantages of artificial nutrition at an early stage so that you can act quickly if necessary.
Neuronal ceroid lipofuscinosis has not yet been fully explored. It can therefore be beneficial, both for oneself and for others, to take part in ongoing studies. In this way, remedies and new therapy methods may be found. In the long term, this could improve the patient’s quality of life. Experimental approaches should not be categorically ruled out. Being open to the latest research on neuronal ceroid lipofuscinosis could, in the long term, make a significant difference in the lives of patients with the disease.
You should also consider seeking psychological help. Losing the ability while fully conscious can be very difficult for patients. In order to counteract and prevent depression and other psychological stress, you should actively work with the help of an experienced psychotherapist.