PhD Scientific Days 2023

Clinical Medicine VI.

A rare neurodegenerative disease in childhood - neuronal ceroid lipofuscinosis

Text of the abstract

Introduction: Neuronal ceroid lipofuscinoses (NCL) are a group of progressive neurodegenerative disorders with intracellular autofluorescent lipopigment accumulation in the central nervous system. It can be traced back to mutations of a total of 13 different genes. Undegraded macromolecules lead to the gradual loss of cognitive functions and the ability to move, sensory damage, ataxia, and epilepsy. Cause-related therapy is currently unavailable.
Objectives, methods: The nature of the neurological symptoms, the order in which they develop, the neuroradiological abnormalities, sometimes a conjunctival biopsy and the knowledge of the gene mutation together make it possible to establish an accurate diagnosis. Our goal was the clinical and molecular diagnosis of patients presenting with neurodegenerative symptoms at the Department of Pediatrics of the University of Debrecen, and the investigation of phenotype-genotype relationships in the case of already diagnosed patients.
Results: Between 2015 and 2020, six children were diagnosed with neuronal ceroid lipufiscinosis at the genetics department of the Pediatrics Institute of the University of Debrecen, two of them siblings. In four cases, the symptoms were caused by a homozygous mutation in the MSFD8 gene, in one case by compound heterozygous mutations of the gene, and in another case by compound heterozygous mutations of the PPT1 gene. (The molecular genetic tests were carried out by the non-independent Department of Clinical Genetics of the University of Debrecen, in close cooperation with our Clinic, and Blueprint Genetics Helsinki).
Findings: The homozygous c.881C>A, p.Thr294Lys mutation of the MFSD8 gene is particularly common in the Roma ethnic group, so in the case of infantile or childhood neurodegenerative disease in this population, this mutation should also be investigated independently. If this mutation cannot be verified, the so-called "single-gene" tests do not make sense - based on the clinical diagnosis, high-throughput next-generation sequencing can help identify the molecular genetic cause. Since it is an autosomal recessive condition, the diagnosis is essential for the subsequent family planning, risk assessment and prenatal diagnosis of the affected families.