CLN4 Disease - Causes, Symptoms, and Treatment

Introduction

CLN4 disease is also called neuronal ceroid lipofuscinosis disease. Neuronal ceroid lipofuscinosis (NCL) disease is a group of diseases that are inherited (a disease carried by children from their parents) and neurodegenerative. Neurodegenerative refers to damage of the neurons, which causes dementia in children. Patients with CLN4 disease suffer from visual impairment, cognitive and motor decline, epilepsy, and premature death. The challenges for primary healthcare to stop the progression of the disease and find potential effective therapies are encouraging. There is a lack of potential treatments for CLN4 diseases. It is possible to stop the sickness from spreading by a combination of treatments.

What Is CLN4 Disease?

CLN4 disease is also known as parry disease, adult neuronal ceroid lipofuscinosis, ceroid lipofuscinosis, neuronal, 4B, autosomal dominant, and CLN4B. It is an adult NCL occurring around 30 years of age. Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative diseases that together form the most common cause of dementia in children. It is a rare disease but affects 1 in one lakh people worldwide. New developments have been made toward potential treatments for NCLs in recent years.

What Are the Causes Of CNL4 Disease?

CLN4 disease is caused by mutations (alteration in the gene structure) in the DNAJC5 gene, which encodes the presynaptic co-chaperone cysteine string protein (CSP). Cysteine string protein is found in the brain, which helps transmit signals in the brain and transmission of nerve impulses. Altered CSP is produced by mutation in the DNAJC5 gene, which affects its function. Therefore, there is an alteration in the transmission of the signals to the brain, which leads to dementia (memory loss) or other mental problems. Due to the lack of proper transmission of the signals, neurological functions are impaired.

What Is the Function of CSP Protein?

CSPα is a highly conserved protein of 198 amino acids that forms compounds. N-terminal "J''-domain (aa 14–83), a linker domain (aa 84–112), the cysteine-string domain (aa 113–135), and a C-terminal domain (aa 136–198) are the composition of the protein. It consists of 14 cysteines in a stretch of 25 amino acids, which is required for initial membrane targeting. CSP activates the adenotriphosphate (ATPase) activity. The primary function of CSP protein is to help transmission of the signals to the brain.

What Are the Symptoms Of CNL4 Disease?

The following are the symptoms of CLN4 disease:

• Generalized seizures (a condition in which uncontrolled shaking movement of limbs occurs).

• Myoclonic jerks (a type of seizure).

• Decline in intellectual and physical function.

• Dementia (a condition that impairs thinking, memory and interferes with daily life).

• Ataxia (a disease in which loss of coordination of voluntary muscle movements occurs).

• Tremors (a disease in which shakiness and uncontrolled movement occur).

• Deterioration of vision.

• Deterioration in speech problems.

• Microcephaly (small size of the brain).

• Difficulty in eating or feeding difficulties.

• Loss of vision may occur.

How to Diagnose CLN4 Disease?

The diagnosis of CLN4 disease is made by clinical evaluation, medical history, and various other tests.

The following are the ways to diagnose CLN4 disease:

• Medical History and Physical Examination - The healthcare providers begin by taking a detailed medical history, which includes the symptoms or any symptoms of mental problems which will look for CLN4 disease. The physical examination done by doctors will detect the signs of neurological abnormalities.

• Neurological Evaluation - The signs of the delayed response to the stimuli (something or an event that causes an organ or tissue to have a particular functional reaction) are detected by the neurologist. They detect these signs by comprehensive evaluation to assist motor skills, cognitive abilities, and overall neurological function.

• Electroencephalogram (EEG) - An easy test that records the electrical activity of the brain. EEG helps to detect the abnormal wave pattern of the brain activity that is seen in the CLN4 disease.

• Genetic Testing - Genetic testing plays a vital role in the diagnosis of CLN4 disease. Genetic testing analyzes the patient's deoxyribonucleoside acid (DNA) to identify the mutation in the CLN4 gene.

• Enzyme Analysis - An enzyme analysis will be performed to measure the activity of the enzyme. There is reduced enzyme activity in neurological disorders.

• Biopsy - A small sample of skin or tissue (biopsy) may be taken to examine the accumulation of lipopigments. Skin fibroblast testing can also be conducted to evaluate the enzymatic activity and confirm the diagnosis.

What Are the Treatments of CLN4 Disease?

No research or study found the picture for CLN4 disease. There is no remedy that can stop the condition's progression. The management of CLN4 disease focuses on providing supportive care or symptomatic treatment to improve the quality of life for the affected individuals.

The following are the common treatments and interventions that may be used:

• Medications: Medications are often prescribed to manage specific symptoms associated with CLN4 disease. These may include antiepileptic drugs to control seizures, muscle relaxants to alleviate muscle stiffness, and medications to manage behavioral or psychiatric symptoms.

• Physical Therapy: The importance of physical therapy in maintaining or improving motor skills and mobility. Physical therapists can create personalized programs, stretching routines, and assistive devices to enhance strength, coordination, and flexibility.

• Occupational Therapy: Occupational therapy helps individuals with CLN4 disease to develop skills and strategies to perform daily activities independently. Occupational therapists may suggest adaptive equipment and techniques to facilitate self-care, communication, and participation in meaningful activities.

• Speech and Language Therapy: Speech and language therapy can assist in managing difficulties related to communication and swallowing. Therapists can provide techniques, exercises, and augmentative and alternative communication (AAC) devices to promote effective communication and support safe swallowing.

• Vision and Hearing Support: As CLN4 disease progresses, individuals may experience vision and hearing impairments. Regular evaluations by ophthalmologists and audiologists can help identify and manage these sensory challenges. Corrective lenses, hearing aids, or other interventions may be recommended to optimize vision and hearing.

• Palliative Care: Given the progressive and devastating nature of CLN4 disease, palliative care plays a crucial role in addressing the physical, emotional, and psychological needs of both the affected individuals and their families. Palliative care focuses on providing comfort, pain management, emotional support, and assistance with end-of-life care.

Conclusion

This neuronal ceroid lipofuscinosis disease being neurodegenerative, causes visual impairment, cognitive and motor decline, epilepsy, and premature death. This neurological disorder is very rare, and patients experience various mental disorders in this disease. However, it can be diagnosed by many methods, as mentioned above. Various medications and therapies are also present to cure this disease. Its treatment is not specific, but it needs the palliative care of the patient. The creation of new genetics-related technologies is also an essential factor in the treatment of this disease. Early detection and appropriate treatment can be attributed to medical intervention that can cure this disease and has a better prognosis.