TY - JOUR
T1 - Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease)
T2 - Expert recommendations for early detection and laboratory diagnosis
AU - Fietz, Michael
AU - AlSayed, Moeenaldeen
AU - Burke, Derek
AU - Cohen-Pfeffer, Jessica
AU - Cooper, Jonathan D.
AU - Dvořáková, Lenka
AU - Giugliani, Roberto
AU - Izzo, Emanuela
AU - Jahnová, Helena
AU - Lukacs, Zoltan
AU - Mole, Sara E.
AU - Noher de Halac, Ines
AU - Pearce, David A.
AU - Poupetova, Helena
AU - Schulz, Angela
AU - Specchio, Nicola
AU - Xin, Winnie
AU - Miller, Nicole
N1 - Publisher Copyright:
© 2016 The Authors
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders. NCLs include the rare autosomal recessive neurodegenerative disorder neuronal ceroid lipofuscinosis type 2 (CLN2) disease, caused by mutations in the tripeptidyl peptidase 1 (TPP1)/CLN2 gene and the resulting TPP1 enzyme deficiency. CLN2 disease most commonly presents with seizures and/or ataxia in the late-infantile period (ages 2–4), often in combination with a history of language delay, followed by progressive childhood dementia, motor and visual deterioration, and early death. Atypical phenotypes are characterized by later onset and, in some instances, longer life expectancies. Early diagnosis is important to optimize clinical care and improve outcomes; however, currently, delays in diagnosis are common due to low disease awareness, nonspecific clinical presentation, and limited access to diagnostic testing in some regions. In May 2015, international experts met to recommend best laboratory practices for early diagnosis of CLN2 disease. When clinical signs suggest an NCL, TPP1 enzyme activity should be among the first tests performed (together with the palmitoyl-protein thioesterase enzyme activity assay to rule out CLN1 disease). However, reaching an initial suspicion of an NCL or CLN2 disease can be challenging; thus, use of an epilepsy gene panel for investigation of unexplained seizures in the late-infantile/childhood ages is encouraged. To confirm clinical suspicion of CLN2 disease, the recommended gold standard for laboratory diagnosis is demonstration of deficient TPP1 enzyme activity (in leukocytes, fibroblasts, or dried blood spots) and the identification of causative mutations in each allele of the TPP1/CLN2 gene. When it is not possible to perform both analyses, either demonstration of a) deficient TPP1 enzyme activity in leukocytes or fibroblasts, or b) detection of two pathogenic mutations in trans is diagnostic for CLN2 disease.
AB - Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders. NCLs include the rare autosomal recessive neurodegenerative disorder neuronal ceroid lipofuscinosis type 2 (CLN2) disease, caused by mutations in the tripeptidyl peptidase 1 (TPP1)/CLN2 gene and the resulting TPP1 enzyme deficiency. CLN2 disease most commonly presents with seizures and/or ataxia in the late-infantile period (ages 2–4), often in combination with a history of language delay, followed by progressive childhood dementia, motor and visual deterioration, and early death. Atypical phenotypes are characterized by later onset and, in some instances, longer life expectancies. Early diagnosis is important to optimize clinical care and improve outcomes; however, currently, delays in diagnosis are common due to low disease awareness, nonspecific clinical presentation, and limited access to diagnostic testing in some regions. In May 2015, international experts met to recommend best laboratory practices for early diagnosis of CLN2 disease. When clinical signs suggest an NCL, TPP1 enzyme activity should be among the first tests performed (together with the palmitoyl-protein thioesterase enzyme activity assay to rule out CLN1 disease). However, reaching an initial suspicion of an NCL or CLN2 disease can be challenging; thus, use of an epilepsy gene panel for investigation of unexplained seizures in the late-infantile/childhood ages is encouraged. To confirm clinical suspicion of CLN2 disease, the recommended gold standard for laboratory diagnosis is demonstration of deficient TPP1 enzyme activity (in leukocytes, fibroblasts, or dried blood spots) and the identification of causative mutations in each allele of the TPP1/CLN2 gene. When it is not possible to perform both analyses, either demonstration of a) deficient TPP1 enzyme activity in leukocytes or fibroblasts, or b) detection of two pathogenic mutations in trans is diagnostic for CLN2 disease.
KW - Expert recommendations
KW - Genetic cause of epilepsy
KW - Laboratory diagnosis
KW - Lysosomal storage disorder
KW - Neurodegeneration
KW - Neuronal ceroid lipofuscinosis
UR - http://www.scopus.com/inward/record.url?scp=84990946251&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2016.07.011
DO - 10.1016/j.ymgme.2016.07.011
M3 - Article
C2 - 27553878
AN - SCOPUS:84990946251
SN - 1096-7192
VL - 119
SP - 160
EP - 167
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 1-2
ER -