A Natural History Study of Late Infantile Variant CLN7 And CLN5 Disease

Neuronal Ceroid Lipofuscinosis (NCL) are comprised of a group of fatal neurodegenerative
diseases caused by mutations in an enzyme or protein which results in the accumulation of
toxic deposits in the eye, brain, skin, muscle and other cells.

CLN7 is a type of NCL caused by homozygous or bi-allelic heterozygous variants in CLN7/MFSD8
gene, whose function is poorly characterized. CLN7 presents with neurological signs,
including blindness, seizures, progressive deterioration in intellectual and motor
capabilities, culminating in premature death in the first or second decade of life.

CLN5 is another type of NCL, caused by homozygous or bi-allelic heterozygous variants in the
CLN5 gene. Lack of CLN5 protein impairs the breakdown of certain proteins, leads to defective
lysosomal trafficking, resulting in accumulation of toxic material and subsequent cell
damage. CLN5 disease presents in childhood with neurological findings including motor
clumsiness and attention disturbances, followed by progressive visual failure, psychomotor
depression, epilepsy, and premature death.

This study aims to prospectively investigate the natural history of CLN7 and CLN5, and
concurrently to identify potential outcome measures that could be used in future clinical
trials. No investigational product will be provided in the study.

Inclusion Criteria:

- Participants must have a diagnosis of CLN7 or CLN5 based on clinical presentation and
genetic testing (known or suspected pathogenic mutation in CLN7/MFSD8 or CLN5 gene).

Exclusion Criteria:

- Patients unable to travel to UT Southwestern Medical Center and Children's Health
Dallas will not be enrolled in the prospective natural history study collecting
standardized clinical data; however, with participant consent, medical records will be
obtained, reviewed, and recorded in the natural history database over time.