At the 15th
International Conference on Neuronal Ceroid Lipfuscinosis (NCL, aka Batten Disease) held in Boston, MA, best practice guidelines for diagnosing neuronal ceroid lipofuscinosis type 2 (CLN2 disease) or Batten disease were presented.
Diagnosing Batten Disease
In May 2015, international experts met to recommend best laboratory practices for early CLN2 diagnosis. The experts recommended that when clinical signs suggest neuronal ceroid lipfuscinosis (NCLs), TPP1 activity should be the first test performed (along with palmitoyl-protein-thioesterase-1 to exclude CLN1).
Unfortunately, getting to that test can take time. The panel noted there are generally 3 phases to getting a CLN2 diagnosis beginning with the suspicion that the child has an unknowns neurological disorder, followed by a general suspicion they have an NCL disorder, followed finally by a specific suspicion they have a CLN disorder.
This diagnostic odyssey is illustrated below.
The experts suggested the following more efficiently diagnose (or rule out) CLN2:
Any unexplained seizure in a child 1 to 9 years of age, particularly with a history of language delays and/or developmental milestone regression should be suspected of having a NCL disorder
When a genetic neurological disorder is suspected, a molecular gene panel test to investigate genetic causes of childhood onset epilepsy or developmental delay is recommended (including a TTP1/CLN2 gene)
When NCL disorders in general are suspected, targeted NCL gene panels may help in diagnosing CLN2
EEG analysis under specific intermittent photic stimulation (1 to 2 Hz) may help diagnose CLN2
Early testing of TPP1 and PPT1 enzyme deficiency can rapidly confirm a diagnosis of CLN2 and CLN1, respectively.
The gold standard for laboratory diagnosis of CLN2 is demonstrating deficient TPP1 activity and detecting causative mutations in each allele of TPP1/CLN2
1. Izzo E, Alsayed M, Burke D, et al. Expert recommendations for the laboratory diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): diagnostic algorithm and best practice guidelines for a timely diagnosis. Presented at the 15th
International Conference on Neuronal Ceroid Lipfuscinosis (Batten Disease); Boston, MA; October 5-8, 2016. Abstract P12.
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