Neuronal ceroid lipofuscinosis: genetic and phenotypic spectrum of 14 patients from Turkey

• DOI: 10.1007/s10072-021-05067-8
• Publication Date: 2021-01-23T22:02:33Z
• Authors: Melis Kose; Engin Kose; Aycan Ünalp; Ünsal Yılmaz; Selvinaz Edizer; Hande Gazeteci Tekin; Pakize Karaoğlu; Taha Reşid Özdemir; Esra Er; Hüseyin Onay; Eser Sozmen Yildirim
• Keywords: Adult; 0301 basic medicine; Epilepsy; Tripeptidyl-Peptidase 1; Turkey; Inborn errors of metabolism; 3. Good health; 03 medical and health sciences; Cross-Sectional Studies; Neuronal ceroid lipofuscinoses; Neuronal Ceroid-Lipofuscinoses; Humans; Neurodegeneration; Child; Cerebral atrophia

Neuronal ceroid lipofuscinoses (NCLs) is a group of congenital metabolic diseases where the neurodegenerative process with the accumulation of ceroid and lipofuscin autofluorescent storage materials is at the forefront. According to the age of presentation, NCLs are classified as congenital, infantile (INCL), late infantile (LINCL), juvenile (JNCL), and adult (ANCL) NCLs. In our study, it was aimed to discuss the clinical and molecular characteristics of our patients diagnosed with NCL.This is a descriptive cross-sectional study which was conducted in 14 patients from 10 unrelated families who were diagnosed with different types of NCL based on clinical presentation, neuroimaging, biochemical measurements, and molecular analyses, at the department of pediatric metabolism between June 2015 and June 2020.A total of 14 patients were diagnosed with different types of NCL. Of those, 4 patients were diagnosed with NCL7 (4/14; 30%), 3/14 (23%) with NCL1, 3/14 (23%) with NCL2, 2/14 (14.2%) with NCL13, and 1/14 (7.1%) with NCL10. Eleven pathogenic variants were detected, 5 of which are novel (c.721G>T [p.Gly241Ter] and c.301G>C [p.Ala146Pro] in MFDS8 gene; c.316C>T [p.Gln106Ter] in PPT1 gene; c.341C>T [p.Ala114Val] in TPP1 gene; c.686A>T [p.Glu229Val] in CTSD gene) CONCLUSION: This study is one of the pioneer comprehensive researches from Turkey that provides information about disease-causing variants and clinical presentation of different and rare types of NCLs. The identification of novel variants and phenotypic expansion is important for genetic counselling in Turkey and expected to improve understanding of NCLs.