A Case Report on the Challenging Diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2)

Andrea Nunes,Emília Katiane Embiruçu Leão,Marielza Veiga,Roberto Giugliani,Joanna Meira,Ana Paula Scholz De Magalhães,Diana Rojas Málaga,Caio Cunha

doi:10.1590/2326-4594-jiems-2020-0010

Abstract

Abstract Neuronal ceroid lipofuscinoses (NCLs), also referred as “Batten disease”, are a group of thirteen rare genetic conditions, which are part of the lysosomal storage disorders. CLN type 2 (CLN2) is caused by the deficient activity of the tripeptidyl peptidase I (TPP1) enzyme, encoded by the TPP1 gene, most frequently leading to the classic late infantile phenotype. Nearly 140 CLN2-causing mutations have been described. In this case report, we describe the identification of a new disease-causing mutation and highlight the importance of appropriate laboratory investigation based on clinical suspicion. The collection of dried blood spots (DBS) on filter paper, which is a convenient sample, can be used to measure the TPP1 enzyme activity and detect CLN2-related mutations. Since the biochemical and genetic diagnoses are possible and as the disease progression is fast and the therapeutic window is short, the investigation of CLN2 should be always considered when this diagnostic hypothesis is raised in order to enable the patients to benefit from the specific pharmacological treatment.

Highlights

Neuronal ceroid lipofuscinoses (NCLs), referred as “Batten disease”, are a group of thirteen neurodegenerative diseases associated with neuronal loss in the cerebellar and cerebral cortex with the accumulation of intralysosomal lipopigments
The diagnosis is confirmed by the finding of low activity of the tripeptidyl peptidase I enzyme (TPP1) in dried blood spot (DBS), leucocytes or cultured fibroblasts, and by the identification of a pathogenic mutation in each of the alleles of the TPP1 gene [4,5,6]
Due to the rapid neurodegenerative progression of NCLs, CLN type 2 (CLN2), early detection is critical to ensure that patients may benefit from the specific treatment, which is currently available [14]

Summary

Introduction

Neuronal ceroid lipofuscinoses (NCLs), referred as “Batten disease”, are a group of thirteen neurodegenerative diseases associated with neuronal loss in the cerebellar and cerebral cortex with the accumulation of intralysosomal lipopigments. The diagnosis is confirmed by the finding of low activity of the tripeptidyl peptidase I enzyme (TPP1) in dried blood spot (DBS), leucocytes or cultured fibroblasts, and by the identification of a pathogenic mutation in each of the alleles of the TPP1 gene [4,5,6] This case report details the diagnostic journey of a patient who presented with speech deterioration, refractory epilepsy and ataxia in the absence of photoparoxysmal response during electroencephalographic evaluations, in whom the diagnosis of late infantile CLN2 was eventually confirmed. Based on the clinical evaluation and on the tests performed, the suspicion of a CLN disease was raised and the step was the measurement of the activities of palmitoyl protein thioesterase 1 (PTT1) and TPP1 enzymes in DBS, to screen for CLN1 and CLN2, respectively These enzyme evaluations were performed when the patient was at 5 years and 6 months of age. Due to the progression of the disease, only supportive treatment is currently provided and includes levetiracetam, clobazam, lamotrigine and phenobarbital to reduce the frequency of epileptic seizures

Discussion

Findings

Ethics Approval and Consent to Participate