ncl disorders: frequent causes of childhood dementia

how to cite this article: schulz a, kohlschütter a. ncl disorders: frequent causes of childhood dementia. iran j child neurol. 2013 winter;7(1):1-8. abstract dementia in children or young adults is most frequently caused by neuronal ceroidlipofuscinoses (ncl), a group of incurable lysosomal storage disorders linked by the accumulation of a characteristic intracellular storage material and progressive clinical deterioration, usually in combination with visual loss, epilepsy, and motor decline. the clinical characteristics can vary and the age at disease onset ranges from birth to over 30 years. diagnosis of an ncl is difficult because of genetic heterogeneity with14 ncl forms (cln1- cln14) identified and a high phenotype variability. a new classification of the disorders is based on the affected gene and the age at disease onset and allows a precise and practicable delineation of every ncl disease. we present a clear diagnostic algorithm to identify each ncl form. a precise diagnosis is essential for genetic counseling of affected families and for optimizing palliative care. as patient management profits from recognizing characteristic complications, care supported by a specialized team of ncl clinicians is recommended. the development of curative therapies remains difficult as the underlying pathophysiological mechanism remains unclear for all ncl forms. refe r ences haltia m. the neuronal ceroid-lipofuscinoses: from past to present. biochim biophys acta 2006;1762:850-6. mole se, williams r, goebel hh, eds. the neuronal ceroid lipofuscinoses (batten disease). 2 ed. contemporary neurology series. oxford university press: oxford, 2011.p. 480. lebrun ah,  moll-khosrawi  p,  pohl  s,  makrypidi  g, storch s, kilian d, et al. analysis of potential biomarkers and modifier genes affecting the clinical course of cln3 disease. mol med 2011;17:1253-61. lebrun ah, storch s, ruschendorf f, schmiedt ml, kyttala a, mole se, et al. retention of lysosomal protein cln5 in the endoplasmic reticulum causes neuronal ceroid lipofuscinosis in asian sibship. hum mutat2009;30:e651-61. kousi m lehesjoki ae, mole se. update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. hum mutat 2011;33:42-63. jalanko a, braulke t. neuronal ceroid lipofuscinoses. biochim biophys acta 2009;1793:697-709. arsov t, smith kr, damiano j, franceschetti s, canafoglia l, bromhead cj, et al. kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in cln6. am j hum genet 2011;88:566-73. smith kr, damiano j, franceschetti s, carpenter s, canafoglia l, morbin m, et al. strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. am j hum genet 2012;90:1102-7. bras j, verloes a, schneider sa, mole se, guerreiro rj. mutation of the parkinsonism gene atp13a2 causes neuronal ceroid-lipofuscinosis. hum mol genet 2012. noskova l, stranecky v, hartmannova h, pristoupilova a, baresova v, ivanek r, et al. mutations in dnajc5, encoding cysteine-string protein alpha, cause autosomal- dominant adult-onset neuronal ceroid lipofuscinosis. am j hum genet 2011;89:241-52. staropoli jf, karaa a, lim et, kirby a, elbalalesy n, romansky sg, et al. a homozygous mutation in kctd7 links neuronal ceroid lipofuscinosis to the ubiquitin- proteasome system. am j hum genet 2012;91:202-8.