neuronal ceroid lipofuscinosis 1

Neuronal ceroid lipofuscinosis 1, often abbreviated CLN1, is a very rare inherited neurodegenerative disorder that primarily affects the brain and nervous system. It results from harmful changes in the PPT1 gene, which codes for the enzyme palmitoyl-protein thioesterase 1; loss of this enzyme leads to toxic buildup of lipopigments inside cells. Age at onset can range from infancy to adulthood, but many children show symptoms within the first few years of life. The condition affects fewer than one person in a million worldwide, and both males and females can be affected equally because the gene is located on an autosome.

CLN1 mainly affects neurological function and development. Early signs often include slowed attainment of motor and language milestones followed by psychomotor deterioration, meaning that skills a child once mastered are gradually lost. Seizures are common and may be the first feature that prompts medical evaluation. Over time many children experience progressive loss of vision, worsening movement control, and significant cognitive decline, reflecting the ongoing accumulation of storage material in nerve cells. Reduced or absent activity of the PPT1 enzyme is a hallmark laboratory finding and helps distinguish CLN1 from other forms of neuronal ceroid lipofuscinosis. Not all individuals experience every feature, and severity varies considerably. Supportive therapies such as physical, occupational, and speech therapy, as well as special education services, can help maintain function and quality of life.

CLN1 is caused by pathogenic variants in the PPT1 gene. The PPT1 protein normally removes fatty acid chains from certain proteins so they can be recycled. When the enzyme is missing or severely reduced, lipopigments build up inside nerve cells and other tissues, leading to progressive cell dysfunction and death. The disorder is inherited in an autosomal recessive pattern, meaning an affected individual has two non-working copies of PPT1, one from each parent. Parents who each carry one altered copy (carriers) are typically healthy but have a 25 percent chance with every pregnancy of having an affected child. This condition is more common when parents share a common ancestor because both are more likely to carry the same rare variant. Genetic counseling is strongly recommended for families to discuss carrier testing and reproductive options.

Currently, management focuses on supportive care and symptom control because no treatments are specifically approved for CLN1. Antiepileptic medications are used to manage seizures, while physiotherapy, occupational therapy, and vision services aim to preserve mobility, independence, and communication for as long as possible. Nutritional support may be required if swallowing difficulties develop. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious, and care is typically coordinated by a multidisciplinary team that may include neurologists, ophthalmologists, rehabilitation specialists, and palliative care providers. Genetic counseling should be offered to affected individuals and their relatives to discuss inheritance and family planning.

CLN1 is generally progressive, and most individuals experience increasing neurological impairment over time; however, the pace of change and the age at which major milestones are lost can differ widely between individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Early intervention with supportive therapies, proactive seizure management, and coordinated specialist follow-up can positively influence quality of life even though a disease-modifying therapy is not yet available. Families often find it helpful to connect with expert centers and patient organizations, and participation in disease registries may provide access to emerging treatments and contribute to research progress.

Several clinical trials are currently investigating new treatment approaches for CLN1, including enzyme replacement strategies and gene-based therapies. Additional therapies have received orphan drug designation and remain in development. Individuals interested in research participation can search ClinicalTrials.gov or consult their healthcare team about eligibility and trial locations.