Neuronal ceroid lipofuscinosis

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at September 24, 2016
StartDiseasesNeuronal ceroid lipofuscinosis

Neuronal ceroid lipofuscinosis (NCLs) is a general term that describes a group of rare neurodegenerative disorders. It is an inherited disease with varying symptoms that are progressive in nature. Patients suffer from escalating and permanent cognitive deficits and impairments in motor control. They may also suffer from seizures and are likely to experience death at an early age. The neuronal ceroid lipofuscinosis category includes at least eight separate neurodegenerative disorders that while genetically different, are all a product of the body’s tissues storing an excessive amount of lipopigments

Contents

Definition & Facts 

Of all neurogenetic disorders involving storage, neuronal ceroid lipofuscinosis is considered the most common. In 1826, Dr. Christian Stengel was the first to report on the condition in a Norwegian medical journal after he studied a family in a small mining town in Norway that had four children affected.

Others to study the disease include F.E. Batten in 1903 and Heinrich Vogt in 1905. For most populations, the occurrence of the disease is one in 12,500. Populations of the United States and northern Europe see a higher occurrence rate at one in 10,000.

Neuronal ceroid lipofuscinosis is typically divided into four main subgroups: adult, juvenile, late infantile and early infantile. The adult form includes Parry disease and Kufs disease. The juvenile subgroup includes Batten disease. The late infantile includes Janksy-Bielschowsky disease.

The subgroup a particular disease falls into depends of factors including the age of the patient when symptoms first appear, the type of early-onset symptoms such as seizures or blindness and the form in which the body accumulates lipofuscin

Symptoms & Complaints 

Symptoms of neuronal ceroid lipofuscinosis may first appear in the form of vision problems or loss of muscle coordination. From there they get progressively worse and involve seizures, dementia, cerebral atrophy, blindness and a loss of cognitive ability.

The diminished ability to control muscle movement makes everyday activities, including walking, difficult. An abnormal increase in muscle spasms is common. Those falling into the early infantile group may appear normal at birth, though symptoms appear by the age of two.

Vision loss is typically the first indicator which rapidly progresses to complete retinal blindness. By three years patients may fall into a persistent vegetative state. By four, brain death may be confirmed.

Late infantile patients start seeing symptoms appear between two and four years of age. These tend to take the form of seizures that are followed by a rapid regression of developmental milestones, including loss of voluntary muscle control. Impairment of vision usually occurs between the ages of four and six and quickly lead to child having only light/dark awareness.

The juvenile form set in between four and 10 years of age. Vision loss that rapidly turns into severe impairment is typically the first sign and occurs within one to two years of onset. Around age ten, epileptic seizures start to occur.

Adult onset of neuronal ceroid lipofuscinosis sets in anywhere after a patient has reached the age of 20. This group suffers from loss of muscle control, seizures and dementia. 

Causes

Neuronal ceroid lipofuscinosis is an inherited disease in which each parent has passed on a non-working copy of the recessive gene. These genes cause an excessive amount of lipopigments to build up in the neuronal cells and various organs of the body. Lipopigments consist of fats and protein and may accumuate in tissues of the kidneys, spleen, liver, and myocardium. It is thought that this buildup happens because the brains of patients develops an inability to remove or recycle proteins. 

Diagnosis & Tests 

Many cases of neuronal ceroid lipofuscinosis are first detected during an eye examination due to vision loss being one of the most prominent first signs. Optometrists are able to identify cell loss in the eyes that occurs with the three forms of childhood onset. From there, patients may be referred to a neurologist for further testing. They will rely on the patient’s medical history and the result of lab testing to make a definitive diagnosis.

Depending on the subtype of the disease, prenatal diagnosis is possible. The category patients will be diagnosed with depends largely on the genes involved and the age of the patient when symptoms are first displayed. Other tests for diagnosis include electroencephalography (EEG), skin biopsy, genetic testing, autofluorescence, electroretinography, blood tests, and brain scans. An EEG can be used to measure the amount of electrical activity occurring in the brain typically involved with seizures.

Skin biopsies can determine whether deposits of lipopigments typical of neuronal ceroid lipofuscinosis are present in tissues. An electroretinogram is an eye test that can detect common vision problems patients of the disease become afflicted with, especially in childhood versions.

Blood tests can also be used to detect deposits of lipopigments. These take on characteristic shapes in the blood. Magnetic resonance imaging (MRI) and computed tomography (CT) scans allow physicians to determine changes in the brain's appearance that are typical of neuronal ceroid lipofuscinosis. 

Treatment & Therapy

There is no cure for neuronal ceroid lipofuscinosis; therefore, treatment typically focuses on slowing the progression of symptoms. Anticonvulsant medications are used to control seizures and therapies for speech and physical therapy for muscle control are used to help the patient remain functioning for as long as may be possible.

Patients suffering from the disease may require a lifetime of care. The younger they are when diagnosed, the greater the risk of the outcome for lifetime disability and early death. An early infantile diagnosis typically leads to death by the age of ten. With a late infantile diagnosis, death between the age of six to early teens is expected. Juvenile onset can lead to a life expectancy between the late teens and early 30s. 

Prevention & Prophylaxis

Because neuronal ceroid lipofuscinosis is an inherited disease, there is nothing that can be done to prevent its occurrence. For those with a family history of the disease, genetic counseling may be an option so that early treatment of symptoms can be established. Prenatal testing for the disease is also recommended for those using in vitro fertilization before implantation.