Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments in the body's tissues. These lipopigments are made up of fats and proteins.
: a storage disease (as Batten disease) marked by abnormal accumulation of lipofuscin in tissues especially of the brain.
Causes. NCL involves the buildup of an abnormal material called lipofuscin in the brain. NCL is thought to be caused by problems with the brain's ability to remove and recycle proteins. Lipofuscinoses are inherited as autosomal recessive traits.
The only specific treatment available for neuronal ceroid lipofuscinoses (NCLs) is cerliponase alfa (Brineura) for neuronal ceroid lipofuscinosis type 2 (CLN2, also known as tripeptidyl peptidase 1 [TPP1] deficiency). Seizures in neuronal ceroid lipofuscinoses (NCLs) should be treated with standard anticonvulsants.
INTRODUCTION. The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage disorders characterized by progressive neurodegeneration and intracellular accumulation of autofluorescent lipopigment.
Lipofuscin is a brownish pigment left over from the breakdown and absorption of damaged blood cells. Lipofuscin is found in heart muscle and smooth muscles. It is also called the aging pigment.
The distinction between ceroid and lipofuscin can be ambiguous in tissue sections. Ceroid typically refers to granules generated during pathological conditions, whereas lipofuscin is used to describe granules accumulating with age in postmitotic tissue (Porta 2002).
Adult neuronal ceroid lipofuscinoses are extremely rare disorders. The prevalence is estimated to be about 1.5 people per 9,000,000 in the general population. Prevalence is the total numbers of individuals with a disease at a given time.
The neuronal ceroid lipofuscinoses (NCLs) are a group of rare and fatal diseases of the nervous system that typically begin in childhood. NCLs are inherited conditions that mostly affect the function of the brain. Some types of NCL are referred to as Batten disease.
About Neuronal ceroid lipofuscinosis
Symptoms:May start to appear at any time in life. Cause:This condition is caused by a change in the genetic material (DNA). Organizations:Patient organizations are available to help find a specialist, or advocacy and support for this specific disease.
In classic infantile neuronal ceroid lipofuscinosis, early development appears normal, but between 6 and 24 months there is rapid psychomotor regression, ataxia, myoclonus, seizures, and visual failure.
Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative disorder presenting in children aged 2–4 years with seizures and loss of motor and language skills, followed by blindness and death in late childhood.
People who develop symptoms of Batten disease as adults have a normal life expectancy. The name for each type of Batten disease starts with “CLN.” This stands for ceroid lipofuscinosis, neuronal — the name of the affected gene.
Vision loss is often the first symptom and can rapidly progress. Parents also often notice clumsiness and stumbling in older children due to a loss of motor coordination. Eventually, children with Batten disease become blind, unable to walk, talk, or swallow, and confined to a wheelchair or bed.
The onset of late infantile Batten disease is between ages two to four. The life expectancy is between ages eight to 10. Juvenile Batten disease occurs in children between ages five and 10. These patients usually live until their late teens or early 20s.
Batten disease is a fatal, inherited disorder of the nervous system that typically begins in childhood. Early symptoms of this disorder usually appear between the ages of 5 and 10 years, when parents or physicians may notice a previously normal child has begun to develop vision problems or seizures.
CLN1 disease is an inherited disorder that primarily affects the nervous system. Individuals with this condition have normal development in infancy, but typically by 18 months they become increasingly irritable and begin to lose previously acquired skills (developmental regression).
: a yellow to brown pigment that is similar in composition to lipofuscin and accumulates in cells chiefly in diseased states and under experimental conditions.
What are the signs and symptoms of neuronal ceroid lipofuscinosis (NCL)? Infantile NCL refers to patients with onset of symptoms prior to age 2. Children may have developmental delays, seizures, slowing of head growth and visual impairment. Over time, neurological symptoms progress and skills are lost.
Currently, there is no treatment to prevent and/or revert lipofuscin-driven retinal degenerative changes.
The age-dependent accumulation of lipofuscin in brain cells is one of the most consistent features of aging. Lipofuscin granules are detectable in a small percentage of neurons in the brains of young children but become progressively and markedly more abundant between the second and ninth decade of life (30).
The dissolution of lipofuscin is not only found in the CNS but also in the myocardium and in the liver. In the latter organs the removal of pigment is carried out by phagocytes towards capillaries. The actual uptake of phagocytes is believed to occur by the process of exocytosis and pinocytosis.
Relation to diseases
Also, pathological accumulation of lipofuscin is implicated in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, certain lysosomal diseases, acromegaly, denervation atrophy, lipid myopathy, chronic obstructive pulmonary disease, and centronuclear myopathy.
Continuous treatment for 8 months with either the natural anti-oxidant Vitamin E (alpha-tocopherol) at 40 mg/mouse/week or the synthetic anti-oxidant butylated hydroxytoluene at about 100 mg/mouse/week diminished significantly the proliferation of lipofuscin granules in spinal cord neurons that developed during that ...