CLN2 disease (late-infantile Batten disease)

Batten disease is the common name for a group of inherited neurodegenerative conditions called neuronal ceroid lipofuscinoses (NCLs). The Batten Disease Family Association (BDFA) explains that they are caused by changes in one of 13 genes, named CLN1 to CLN14 with no CLN9, and that they disrupt lysosomes, the cell recycling compartments. Nerve cells are especially vulnerable, which leads to progressive loss of vision, seizures, cognitive decline, loss of speech, movement difficulty and early death. The BDFA estimates that between 110 and 150 people in the UK are affected by any form of Batten disease.

CLN2 disease, caused by TPP1 variants, is the best-known type because it is the only one with a specific treatment. MedlinePlus counts more than 300 cases described worldwide in the scientific literature, and higher incidence in the Canadian province of Newfoundland.

Children seem to develop normally at first, meeting early milestones such as crawling, walking and talking. Symptoms typically begin between ages 2 and 4 with recurrent seizures and difficulty coordinating movement. Muscle twitches and vision loss follow. Motor skills, sitting and walking, and speech are affected, and children lose skills they had acquired, with worsening intellectual disability and behavioural problems. Many need a wheelchair by late childhood and typically do not survive past their teens.

Some children develop symptoms later, usually after age 4. They tend to have milder features overall but more severe unsteadiness, and may survive into adulthood.

Early speech delay or a first unprovoked seizure in a toddler who was developing well should lead to a neurological opinion and, where suspected, a TPP1 enzyme test, because delays in diagnosis mean delays in any treatment.

Paediatric neurologists look for the pattern of seizures, regression and vision change, supported by an EEG, MRI of the brain and eye assessment. A blood test for tripeptidyl peptidase 1 enzyme activity and genetic testing of TPP1 confirm CLN2 disease. Genetic counselling is offered to the family because the condition is autosomal recessive, so each child of two carriers has a 1 in 4 chance of being affected.

Cerliponase alfa is an enzyme replacement therapy for CLN2. It has been available to children in England through a managed access agreement. NICE reviewed it again, and highly specialised technologies guidance 34, dated 18 February 2026, does not recommend cerliponase alfa for treating CLN2 within its marketing authorisation. This replaced earlier guidance, HST12.

NICE explains that clinical trial evidence shows cerliponase alfa slows the progression of CLN2 and that clinical and patient experts described it as a transformative treatment, but long-term evidence is limited and, at the proposed price, the cost-effectiveness estimate was not within what NICE considers an acceptable use of NHS resources. Importantly, the guidance is not intended to affect treatment that was funded through managed access: children already receiving it, or who start before the managed access period ends, can continue until they, their clinician and their parents or carers agree it is time to stop.

The BDFA states that apart from this treatment, available care manages symptoms rather than the underlying cause. Families may wish to ask the specialist team about the current position in England, Scotland, Wales and Northern Ireland, because commissioning can differ and decisions can be revisited.

Standard care without cerliponase alfa is supportive and aims to relieve symptoms and maintain function and quality of life. That includes anti-seizure medicines, physiotherapy and equipment, feeding and swallowing support, and management of sleep, pain, drooling and muscle stiffness. Palliative care teams and children's hospices can support families from early in the illness.

The BDFA provides family support, information on types of Batten disease and a research newsletter, and advocates for modern neurological services.

Call 999 for a seizure that lasts longer than the time in the care plan, repeated seizures without recovery, choking that does not clear, or difficulty breathing. Contact the specialist team promptly for fever, new drowsiness or any sudden change in behaviour.