Ceroid lipofuscinosis type 2 disease: Effective presymptomatic therapy-Oldest case of a presymptomatic enzyme therapy

Eur J Neurol. 2024 Sep;31(9):e16324. doi: 10.1111/ene.16324. Epub 2024 May 1.

Abstract

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, lysosomal storage disorder that causes pediatric onset neurodegenerative disease. It is characterized by mutations in the TPP1 gene. Symptoms begin between 2 and 4 years of age with loss of previously acquired motor, cognitive, and language abilities. Cerliponase alfa, a recombinant human TPP1 enzyme, is the only approved therapy. We report the first presymptomatic cerliponase alfa intraventricular treatment in a familial case of CLN2 related to a classical TPP1 variant. Sister 1 presented with motor, cognitive, and language decline and progressive myoclonic epilepsy since the age of 3 years, evolved with severe diffuse encephalopathy, received no specific treatment, and died at 11 years. Sister 2 had a CLN2 presymptomatic diagnosis and has been treated with cerliponase since she was 12 months old. She is now 6 years 8 months and has no CLN2 symptom except one generalized seizure 1 year ago. No serious adverse event has occurred. Repeated Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition standardized index scores are heterogeneous in the extremely low to low average ranges. Mean length of utterances, a global index of sentence complexity, showed a delay, but a gradual improvement. The reported case enhances the major contribution of presymptomatic diagnosis and significant middle-term treatment benefit for patients with CLN2.

Keywords: CLN2; TPP1; case report; cerliponase; presymptomatic.

Publication types

  • Case Reports

MeSH terms

  • Aminopeptidases* / genetics
  • Child
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases* / genetics
  • Enzyme Therapy
  • Female
  • Humans
  • Neuronal Ceroid-Lipofuscinoses* / complications
  • Neuronal Ceroid-Lipofuscinoses* / drug therapy
  • Neuronal Ceroid-Lipofuscinoses* / genetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Serine Proteases* / genetics
  • Tripeptidyl-Peptidase 1*

Substances

  • Tripeptidyl-Peptidase 1
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • TPP1 protein, human
  • Serine Proteases
  • Aminopeptidases
  • cerliponase alfa
  • Recombinant Proteins

Supplementary concepts

  • Ceroid Lipofuscinosis, Neuronal, 2