Late Talkers in Late Infantile CLN2 Disease: Red Flag for an Early Diagnosis

Aims: Late-infantile CLN2 disease is caused by a deficiency of the lysosomal enzyme tripeptidyl peptidase 1 and is characterized by rapid psychomotor decline and epilepsy. Although the disease is presently incurable, early diagnosis is desirable for family planning. In our patients, diagnosis was frequently delayed by 2 or more years after the onset of striking symptoms (epilepsy and ataxia). We were looking for possible forerunners of the overt manifestation of the disease.

Methods: As an abnormal language development has occasionally been reported, we reviewed systematically the early development of 28 patients, focusing on language acquisition.

Results: Two-thirds of patients never achieved language capacities in the normal range for age. Most of these children had been classified as “late talkers.”

Conclusion: “Late talkers” have an increased risk to be presymptomatic CLN2 patients. The availability of a simple and cheap enzymatic dry blood spot test helps clarifying a suspicion of this severe genetic disease fast and conveniently.

Keywords: CLN2, late talkers.