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Ceroid lipofuscinosis, neuronal, 1 (CLN1)

Genes

  • Palmitoyl-protein thioesterase 1 (PPT1)

Summary

Ceroid lipofuscinosis, neuronal, 1 (CLN1) was originally described as the infantile-onset form of neuronal ceroid lipofuscinosis (INCL), or the infantile-onset Finnish form of neuronal ceroid lipofuscinosis, having first been described in that population. With the identification of molecular defect, the CLN1 refers to CLN caused by mutation in the PPT1 gene, regardless of the age at onset. The classic INCL form of CLN1 is a severe deteriorating central nervous system disease of young infants caused by dysfunction of the lysosomal enzyme PPT1 (palmitoyl protein thioesterase 1) encoded by a gene at chromosome 1q32. The first clinical signs of INCL usually present at the age of 6 to 12 months after a normal newborn and early infancy period with muscular hypotonia and cessation of developmental progress. Skills learned earlier disappear and growth curve of head circumference levels off. Epileptic convulsions and visual loss occur slightly later between the age of one and two years. Deterioration continues rapidly and by the age of three to four years INCL children are deeply retarded without cortical functions and with an isoelectric EEG recording. Death occurs several years later often during the second decade. At autopsy, extreme brain atrophy is seen with an average weight of only 250 to 450 g (age matched normal weight ca 1000g). The cerebral cortex is almost totally replaced by glial tissue, showing accumulating autofluorescent material, lipofuscin. The accumulating substance is mostly composed of saposins A and D. Clinical diagnosis of INCL can be confirmed by gene test of the founder mutation, and also by assay of the activity of PPT1 enzyme in peripheral blood leukocytes. The same studies on a chorionic villus biopsy allow prenatal diagnosis of INCL. In addition to the classic clinical phenotype, CLN1disease has also been associated with phenotypes of later onset: late infantile, juvenile, and adult.

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UMLS Concept names

Selected publications

  • 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. 2012 Jan;33(1):42-63. (Pubmed)