Pre- and postnatal diagnosis of patients withCLN1 and CLN2 by assay of palmitoyl protein thioesterase and tripeptidyl peptidase I activities

Palmitoyl-protein thioesterase (PPT) and tripeptidyl-peptidase I (TPP-I) activities were measured in leucocytes andfibroblasts. Fourteen patients were confirmed as having late infantile neuronal ceroid lipofuscinosis due to a deficiency of TPP-I activity. This included one patient with a milder and more protracted form of the disease. In addition this enzyme deficiency was found in a clinically normal younger sibling of a patient. Of particular importance was the finding of normal TPP-I activity in two patients who had been diagnosed as having classical late infantile neuronal ceroid lipofuscinosis. A deficiency of PPT was confirmed retrospectively in stored fibroblasts from two patients who had already died having been diagnosed with infantile neuronal ceroid lipofuscinosis. Palmitoylprotein thioesterase or TPP-I activities were measured in chorionic villi and cultured chorionic villi cells in three pregnancies. The enzyme results were confirmed by mutational analysis if the mutations were known, or, in the case of the pregnancy at risk for infantile neuronal ceroid lipofuscinosis by electron microscopy of the chorionic villi. Our results show that assay of PPT and TPP-I is reliable in the diagnosis of patients with mutations in the CLN1 and CLN2 genes. It is imperative to assay these enzymes in all patients to confirm the diagnosis and ensure accurate genetic counselling of other family members. Once an enzyme deficiency has been confirmed reliable prenatal diagnosis is available even if both mutations have not been detected.