BabyScreen+ newborn screening

Gene: TPP1

Green List (high evidence)

Tripeptidyl-peptidase 1 deficiency (synonym: CLN2 disease) is a rare, autosomal recessive, pediatric neurodegenerative disease resulting from pathogenic variants in the gene encoding lysosomal enzyme tripeptidyl peptidase 1 (TPP1).

Affected children are functionally normal until the age of 2 to 4 years and subsequently have seizures and delayed language acquisition followed by a rapid decline in motor, language, cognitive, and visual function over a period of 4 to 6 years and death by early adolescence.

A deficiency of TPP1 results in accumulation of lysosomal storage material that causes degenerative changes in neurons throughout the central nervous system and retina.

TPP! enzyme activity can be measured in WBC

Cerliponase alfa ERT prevents, halts, or slows clinical deterioration. It may end up being available through the lifesaving drugs program in due course

Also causes SCAR7 - onset generally after 5 yr, but some before then - not known if ERT will impact on the clinical course of this allelic disorder

Created: 24 Dec 2022, 3:31 a.m. | Last Modified: 24 Dec 2022, 3:31 a.m.

Panel Version: 0.1675

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neruodegeneration; seizures; loss of vision; loss of language

Publications

• PMID: 30783219
• PMID: 32280231

I don't know

Definitive gene disease association
Early onset neurodegenerate disease (from about age 2), seizures, ID, visual problems
Treatment: cerliponase alfa enzyme replacement (Brineura - approved in Australia since 2018) *worth checking this is actually available? Ask chloe?

Created: 29 Nov 2022, 3:37 a.m. | Last Modified: 29 Nov 2022, 3:37 a.m.

Panel Version: 0.1121

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ceroid lipofuscinosis, neuronal, 2 MIM#204500 (Batten disease)

Publications

• PMID: 32684372, PMID: 31884868, PMID: 30470609, PMID: 33882967