Approach Considerations

The only specific treatment available for neuronal ceroid lipofuscinoses (NCLs) is cerliponase alfa (Brineura) for neuronal ceroid lipofuscinosis type 2 (CLN2, also known as tripeptidyl peptidase 1 [TPP1] deficiency). Cerliponase alfa, a drug that requires intraventricular administration, was approved by the FDA in April 2017 to slow the loss of ambulation in symptomatic pediatric patients aged 3 years or older with late infantile neuronal CLN2. Approval was based on a nonrandomized, single-arm dose escalation study over 96 weeks. Results were compared with untreated patients from a natural history cohort. Twenty-four patients aged 3-8 years were enrolled in the clinical study. One patient withdrew after week 1 due to inability to continue with study procedures; 23 patients were treated with cerliponase alfa every other week for 48 weeks and continued treatment during the extension. Twenty-two patients were evaluated at week 96, 21 (95%) did not have a decline in the motor domain of the CLN2 clinical rating scale. Only the patient who terminated early was deemed to have a decline in the motor domain of the CLN2 clinical rating scale.^[25]

Bone marrow transplantation has been tried in animal models as well as in a few infants, with disappointing results. Vitamin E and other antioxidants, as well as selenium, have been tried without significant efficacy. Seizures should be treated with standard anticonvulsants.^[26]

Future treatments may involve stem cell transplantation, enzyme replacement, gene therapy, and/or immune therapy.^{[27, 28]}

A study regarding the safety and preliminary efficacy of CNS stem cell transplantation in patients with palmitoyl protein thioesterase 1 (PPT1) or tripeptidyl peptidase 1 (TTP1) deficiency is currently ongoing.^[29]

Replication-deficient adeno-associated virus gene transfer vector (AAV2-mediated CLN2 gene transfer) has been studied in mice, rats, and nonhuman primates. Studying this in children is of interest.^{[30, 31, 32, 33]}

Consultations

Consultation with a geneticist is helpful because prenatal diagnosis may be possible—using DNA analysis and electron microscopy of chorionic villus samples—for families with an affected child.^[34]Genetic counseling would include a discussion about the mode of inheritance and risks for recurrence so that couples can make rational family planning decisions.

An ophthalmologist consultation can be very helpful in the evaluation of children thought to have NCL, since abnormal findings may be noted on funduscopic examination, electroretinography, and/or fluorescein angiography.

Consultation by a physiatrist (physical medicine and rehabilitation physician) is very helpful to manage spasticity, therapy, and equipment needs.

Medication

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