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23.01.2021 | Original Article

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

verfasst von: 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

Erschienen in: Neurological Sciences | Ausgabe 3/2021

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Abstract

Introduction and purpose

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.

Material and method

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.

Results

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.

Haltia M, Goebel HH (2013) The neuronal ceroid-lipofuscinoses: a historical introduction. Biochim Biophys Acta (BBA) - Mol Basis Dis 1832(11):1795–1800. https://doi.org/10.1016/j.bbadis.2012.08.012CrossRef

Ren X-T, Wang X-H, Ding C-H, Shen X, Zhang H, Zhang W-H, Li J-W, Ren C-H, Fang F (2019) Next-generation sequencing analysis reveals novel pathogenic variants in four Chinese siblings with late-infantile neuronal ceroid lipofuscinosis. Front Genet 10:370. https://doi.org/10.3389/fgene.2019.00370CrossRefPubMedPubMedCentral

Lewis G, Morrill AM, Conway-Allen SL, Kim B (2020) Review of cerliponase alfa: recombinant human enzyme replacement therapy for late-infantile neuronal ceroid lipofuscinosis type 2. J Child Neurol 35(5):348–353. https://doi.org/10.1177/0883073819895694CrossRefPubMed

Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R (2013) NCL diseases—clinical perspectives. Biochim Biophys Acta 1832(11):1801–1806. https://doi.org/10.1016/j.bbadis.2013.04.008CrossRefPubMedPubMedCentral

Radke J, Stenzel W, Goebel HH (2015) Human NCL neuropathology. Biochim Biophys Acta (BBA) - Mol Basis Dis 1852(10):2262–2266. https://doi.org/10.1016/j.bbadis.2015.05.007CrossRef

Williams RE, Mole SE (2012) New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology 79(2):183–191. https://doi.org/10.1212/WNL.0b013e31825f0547CrossRefPubMed

Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschütter A (2018) Study of intraventricular cerliponase Alfa for CLN2 disease. N Engl J Med 378(20):1898–1907. https://doi.org/10.1056/NEJMoa1712649CrossRefPubMed

Katz ML, Tecedor L, Chen Y, Williamson BG, Lysenko E, Wininger FA, Young WM, Johnson GC, Whiting REH, Coates JR, Davidson BL (2015) AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease. Sci Transl Med 7(313):313ra180. https://doi.org/10.1126/scitranslmed.aac6191CrossRefPubMedPubMedCentral

Shyng C, Nelvagal HR, Dearborn JT, Tyynelä J, Schmidt RE, Sands MS, Cooper JD (2017) Synergistic effects of treating the spinal cord and brain in CLN1 disease. Proc Natl Acad Sci U S A 114(29):E5920–E5929. https://doi.org/10.1073/pnas.1701832114CrossRefPubMedPubMedCentral

10.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424. https://doi.org/10.1038/gim.2015.30CrossRefPubMedPubMedCentral

11.

Topçu M, Tan H, Yalnýzoðlu D, Usubütün A, Saatçi I, Aynacý M, Anlar B, Topaloðlu H, Turanlý G, Köse G, Aysun S (2004) Evaluation of 36 patients from Turkey with neuronal ceroid lipofuscinosis: Clinical, neurophysiological, neuroradiological and histopathologic studies. Turk J Pediatr 46(1):103

12.

Cardona F, Rosati E (1995) Neuronal ceroid-lipofuscinoses in Italy: an epidemiological study. Am J Med Genet 57(2):142–143. https://doi.org/10.1002/ajmg.1320570206CrossRefPubMed

13.

Claussen M, Heim P, Knispel J, Goebel HH, Kohlschütter A (1992) Incidence of neuronal ceroid-lipofuscinoses in West Germany: variation of a method for studying autosomal recessive disorders. Am J Med Genet 42(4):536–538. https://doi.org/10.1002/ajmg.1320420422CrossRefPubMed

14.

Uvebrant P, Hagberg B (1997) Neuronal ceroid lipofuscinoses in Scandinavia. Epidemiology and clinical pictures. Neuropediatrics 28(1):6–8. https://doi.org/10.1055/s-2007-973654CrossRefPubMed

15.

Kirveskari E, Partinen M, Santavuori P (2001) Sleep and its disturbance in a variant form of late infantile neuronal ceroid lipofuscinosis (CLN5). J Child Neurol 16(10):707–713. https://doi.org/10.1177/088307380101601001CrossRefPubMed

16.

Maganti R, Hausman N, Koehn M, Sandok E, Glurich I, Mukesh BN (2006) Excessive daytime sleepiness and sleep complaints among children with epilepsy. Epilepsy Beha 8(1):272–277. https://doi.org/10.1016/j.yebeh.2005.11.002CrossRef

17.

Heikkilä E, Hàtònen TH, Telakivi T, Laakso ML, Heiskala H, Salmi T, Alila A, Santavuori P (1995) Circadian rhythm studies in neuronal ceroid-lipofuscinosis (NCL). Am J Med Genet 57(2):229–234. https://doi.org/10.1002/ajmg.1320570223CrossRefPubMed

18.

Lehwald LM, Pappa R, Steward S, de los Reyes, E. (2016) Neuronal ceroid lipofuscinosis and associated sleep abnormalities. Pediatr Neurol 59:30–35. https://doi.org/10.1016/j.pediatrneurol.2016.02.009CrossRefPubMed

19.

Vanhanen SL, Raininko R, Autti T, Santavuori P (1995) MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis. Part 2: MRI findings in 21 patients. J Child Neurol 10(6):444–450. https://doi.org/10.1177/088307389501000604CrossRefPubMed

20.

Aungaroon G, Hallinan B, Jain P, Horn PS, Spaeth C, Arya R (2016) Correlation among genotype, phenotype, and histology in neuronal ceroid lipofuscinoses: an individual patient data meta-analysis. Pediatr Neurol 60:42–48.e4. https://doi.org/10.1016/j.pediatrneurol.2016.03.018CrossRefPubMed

21.

Mole SE, Anderson G, Band HA, Berkovic SF, Cooper JD, Kleine Holthaus S-M, McKay TR, Medina DL, Rahim AA, Schulz A, Smith AJ (2019) Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis. Lancet Neurol 18(1):107–116. https://doi.org/10.1016/S1474-4422(18)30368-5CrossRefPubMed

22.

Smith KR, Dahl H-HM, Canafoglia L, Andermann E, Damiano J, Morbin M, Bruni AC, Giaccone G, Cossette P, Saftig P, Grötzinger J, Schwake M, Andermann F, Staropoli JF, Sims KB, Mole SE, Franceschetti S, Alexander NA, Cooper JD et al (2013) Cathepsin F mutations cause type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis. Hum Mol Genet 22(7):1417–1423. https://doi.org/10.1093/hmg/dds558CrossRefPubMedPubMedCentral

23.

Bras J, Djaldetti R, Alves AM, Mead S, Darwent L, Lleo A, Molinuevo JL, Blesa R, Singleton A, Hardy J, Clarimon J, Guerreiro R (2016) Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer’s disease identifies a homozygous CTSF mutation. Neurobiol Aging 46:236.e1–236.e6. https://doi.org/10.1016/j.neurobiolaging.2016.06.018CrossRef

24.

Wang C, Xu H, Yuan Y, Lian Y, Xie N, Ming L (2018) Novel compound heterozygous mutations causing Kufs disease type B. Int J Neurosci 128(6):573–576. https://doi.org/10.1080/00207454.2017.1403439CrossRefPubMed

25.

Doccini S, Sartori S, Maeser S, Pezzini F, Rossato S, Moro F, Toldo I, Przybylski M, Santorelli FM, Simonati A (2016) Early infantile neuronal ceroid lipofuscinosis (CLN10 disease) associated with a novel mutation in CTSD. J Neurol 263(5):1029–1032. https://doi.org/10.1007/s00415-016-8111-6CrossRefPubMed

26.

Fritchie K, Siintola E, Armao D, Lehesjoki A-E, Marino T, Powell C, Tennison M, Booker JM, Koch S, Partanen S, Suzuki K, Tyynelä J, Thorne LB (2009) Novel mutation and the first prenatal screening of cathepsin D deficiency (CLN10). Acta Neuropathol 117(2):201–208. https://doi.org/10.1007/s00401-008-0426-7CrossRefPubMed

27.

Varvagiannis K, Hanquinet S, Billieux M, De Luca R, Rimensberger P, Lidgren M, Guipponi M, Makrythanasis P, Blouin J, Antonarakis S, Steinfeld R, Kern I, Poretti A, Fluss J, Fokstuen S (2018) Congenital neuronal ceroid lipofuscinosis with a novel ctsd gene mutation: a rare cause of neonatal-onset neurodegenerative disorder. Neuropediatrics 49(02):150–153. https://doi.org/10.1055/s-0037-1613681CrossRefPubMed

Titel: Neuronal ceroid lipofuscinosis: genetic and phenotypic spectrum of 14 patients from Turkey
verfasst von: 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
Publikationsdatum: 23.01.2021
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 3/2021
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-021-05067-8

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Introduction and purpose

Material and method

Results

Conclusion

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