Neuronal ceroid lipofuscinosis: an ultrastructural, genetic, and clinical study report.
The term "neuronal ceroid lipofuscinosis" (NCL) describes a complex of inherited neurodegenerative conditions associated with storage of lipopigments in brain tissue. In 1989 Dyken proposed a classification of NCL based on the age, clinical symptoms, and ultrastructural aspects of the lipopigments. At the ultrastructural level it is possible to distinguish 5 different patterns of osmiophilic lipopigments: usual lipofuscin, fingerprint deposits, granular profiles, curvilinear bodies, and microtubular aggregates. The concept that each ultrastructural pattern was the counterpart of a specific clinical type has been proved not to be true. Advances in molecular genetic techniques have allowed the identification of defective genes and their protein products in several NCL clinical forms. Ceroid lipofuscin deposits may be ultrastructurally observed not only in neuronal cells, but also in several other sites, such as trophoblastic cells, thus permitting prenatal diagnosis. In spite of recent advances in immunohistochemical identification of biochemical markers, the ultrastructural identification of lipofuscinic pigments remains the gold standard to identify NCL, together with clinical aspects and respective gene defects. This study describes the ultrastructural aspects observed in 8 cases of NCL syndromes (3 juvenile, 3 infantile, 1 late infantile, and 1 congenital clinical form). In these patients, genetic analysis was also performed.
Boldrini
R
R
Dipartimento di Anatomia Patologia, Ospedale Pediatrico Bambino Gesù, Roma, Italy.
Biselli
R
R
Santorelli
F M
FM
Bosman
C
C
D002566:Ceroid; D002648:Child; D002675:Child, Preschool; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008062:Lipofuscin; D008214:Lymphocytes / Q000201:enzymology; D020140:Lysosomal Storage Diseases, Nervous System; D008247:Lysosomes / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology*; D009474:Neurons / Q000648:ultrastructure*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis; D013869:Thiolester Hydrolases
D002566:Ceroid; D008062:Lipofuscin; D008565:Membrane Proteins; D012313:RNA; D013869:Thiolester Hydrolases; C416054:PPT1 protein, human