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An international team of experts has developed a set of consensus-based and family-based recommendations for the diagnosis and best management of care for neuronal ceroid lipofuscinosis type 1 (CLN1).

The guidelines were described in a report, “Management of CLN1 disease: international clinical consensus», Published in the journal Pediatric neurology.

Originally called infantile Batten disease, CLN1 is a rare inherited neurodegenerative disease caused by a deficiency of the enzyme PPT1 due to mutations in the CLN1 uncomfortable. PPT1 deficiency results in the toxic accumulation of lipofuscins, made up of fats and proteins, inside the recycling centers of cells.

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A CLN1 diagnosis is often missed or delayed because of its rarity, but also because symptoms overlap with those of other conditions. Clinical features include developmental delay, cognitive and motor decline, vision loss, seizures, and difficulty walking and maintaining balance.

“In the classic form of CLN1 disease, symptoms begin in infancy; Additional [forms] have been observed with infantile, juvenile and late adult onset, ”the researchers wrote.

Currently, no disease-modifying therapy is available for the disease, and there are no specific clinical management guidelines or consensus statements.

As such, “families affected by CLN1 disease have led an international initiative to develop a consensus statement on clinical care based on the advice of clinicians, researchers and patient advocates with direct experience of care. to patients with CLN1 disease, ”the researchers wrote.

This family-clinician partnership was created by Taylor’s tale, a nonprofit rare disease patient advocacy group.

A systematic review of the published evidence was conducted to develop key statements, which were discussed in a meeting and supported by online questionnaires specific to experts and caregivers.

The expert-specific survey was completed by 15 experts from seven countries on four continents. These included 10 pediatric neurologists, a neuropsychologist, a metabolism specialist, a developmental physiotherapist, a palliative care nurse and a social worker. The caregiver-specific survey was carried out by 39 primary caregivers from six countries.

Statements that reached consensus became guidelines for care.

Key themes

The report focused on 14 key topics: clinical spectrum; early diagnosis; disease management; convulsions; movement disorders; cognitive impairment; eyesight problems; physiotherapy, occupational therapy and speech therapy; nutritional, gastrointestinal, respiratory and anesthetic management; sleep disturbances; pain and distress; mood and behavior symptoms; end of life care; and family support.

Regarding the clinical spectrum, the panel agreed that disease varies with age of onset, order of symptom onset, rate of disease progression and life expectancy. . Therefore, determining the specific form is essential to predict clinical course, prognosis, and care needs, and then tailor disease management.

The infantile form typically develops between 6 and 18 months, the late infantile form between 18 months and 4 years, the juvenile form after 4 years and until early adolescence and the adult form in late adolescence or adulthood.

According to caregivers’ responses, the infantile form is the most common (51%), followed by the late infantile and juvenile forms (both representing about 20% of cases). In general, the older the age of onset of symptoms, the slower the disease progression.

Additionally, early diagnosis “is essential to ensure optimal symptom management, minimize complications, and connect families to appropriate psychosocial support and genetic counseling,” the team wrote.

CLN1 disease should be considered in young children over 6 months of age with developmental stabilization or regression, slowing of head growth and / or treatment-resistant seizures, as well as in older children. school with a combination of visual loss, dementia or seizures.

Although the adult form is “incredibly rare”, adults with progressive visual, cognitive, motor and / or behavioral abnormalities should be tested for CLN1 disease.

According to caregivers, the first symptoms that most often prompted medical attention included motor retardation or decline (36%), vision decline (22%), learning delay or decline (14%) and seizures (14%).

The diagnosis can be confirmed by genetic testing looking for pathogenic mutations in the CLN1 gene and / or by PPT1 enzymatic test.

Management of CLN1 disease should focus on minimizing symptoms and maximizing the quality of life for the patient and their family. Symptom management can include “a wide range of strategies: pharmacological and non-pharmacological therapy, nutrition, psychosocial and school support, palliative care, and palliative care support,” the researchers wrote.

As such, ongoing management often involves a multidisciplinary clinical team, in which regular communication and coordination of care is essential, they added.

Most (72%) of caregivers believed that the interventions they were using helped improve their child’s quality of life. The most common interventions included anti-epileptic drugs, physical therapy, massage, home / school modifications, and dietary changes.

Regarding seizures, which may become less problematic over time, the panel recommended prescribing optimal antiepileptic drugs based on the type of seizure and exploring non-pharmacological approaches, such as ketogenic diet.

Since seizures may never be completely eliminated, a balance between seizure reduction and the side effects of antiepileptic drugs should be attempted.

Doctors need to determine whether movement problems are intrinsic to the disease or to side effects of therapy, and then focus treatment on those causing the functional impairments.

Experts recommended that occupational therapy, physiotherapy and speech therapy be initiated early in the course of the disease, and that swallowing dysfunction and the risk of aspiration (food or fluid entering the lungs) be assessed. when motor function decreases.

Motor and vision problems were ranked by caregivers as the symptoms with the greatest unmet need for therapeutic intervention. Yet, they considered physiotherapy and occupational therapy to be the most effective ways to manage symptoms of CLN1 disease, after anti-seizure drugs.

“Everything in their short life should make them as happy and comfortable as possible. When the vision disappears, listen to more music and let them enjoy their favorite movies. Ask yourself ‘Am I going to regret that I didn’t do this’ and do it,’ the caregivers said.

Patients should also be provided with “nutritional supports, modified diets and / or other feeding routes as needed,” the team wrote.

Caregivers should follow the recommended immunization schedules for their affected child in order to reduce lung infections and promote positive sleep hygiene practices to manage their child’s sleep disturbances, which caregivers say affect almost everyone ( 91%) patients with CLN1.

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“Some caregivers have reported that pediatric hospice palliative care options are not readily available in many places and that hospice providers are largely inexperienced with pediatric cases,” the team wrote, adding that there is a need extra support “to make families more comfortable when the going gets tough.”

In addition, “goals and strategies should be reassessed over time and adapted to current patient needs, with the primary goal of optimizing the quality of life for patients and their families,” the experts wrote.

It also includes providing community / psychosocial support to families, especially siblings, whose needs “may be overlooked due to the urgent needs of the patient with CLN1 disease,” they added.

Helping family / friends (18%) or respite / other caregivers (16%) can make the biggest difference, as well as connecting through social media (14%) and external support groups (11%). , among other support strategies.