Diagnosis of the neuronal ceroid lipofuscinoses: An update

Abstract

For the majority of families affected by one of the neuronal ceroid lipofuscinoses (NCLs), a biochemical and/or genetic diagnosis can be achieved. In an individual case this information not only increases understanding of the condition but also may influence treatment choices and options. The presenting clinical features prompt initial investigation and also guide clinical care. The clinical labels "infantile NCL", "late infantile NCL" and "juvenile NCL", therefore remain useful in practice. In unusual or atypical cases ultra-structural analysis of white blood cells or other tissue samples enables planning and prioritisation of biochemical and genetic tests. This review describes current methods available to achieve clinical, pathological, biochemical and genetic diagnosis in children presenting with symptoms suggestive of one of the NCLs.

Mutations in palmitoyl-protein thioesterase 1 alter exocytosis and endocytosis at synapses in Drosophila larvae

“…6 The infantile onset form of the disease (INCL) is one of the more severe forms, with symptoms such as blindness, ataxia, and mental decline beginning to appear by 6-12 mo of age. [7][8][9] Mutations in the soluble lysosomal enzyme Ppt1 are the underlying molecular cause of the disease, but it is still unclear why the loss of this ubiquitously expressed protein produces a very specific neurodegenerative phenotype. 4 The disease phenotype provides further support that efficient Infantile-onset neuronal ceroid lipofuscinosis (INCL) is a severe pediatric neurodegenerative disorder produced by mutations in the gene encoding palmitoyl-protein thioesterase 1 (Ppt1).…”

Mutations in MFSD8/CLN7 are a frequent cause of variant-late infantile neuronal ceroid lipofuscinosis

“…The neuronal ceroid lipofuscinoses (NCL) are a heterogeneous group of pediatric neurodegenerative disorders (Mole et al, 2005;Haltia, 2006;Williams et al, 2006) sharing the clinical symptoms of macular-cerebral OFFICIAL JOURNAL www.hgvs.org…”

Neuronal ceroid-lipofuscinoses

“…Histochemically, lysosomal acid phosphatase activity is associated with the storage material. Immunohistochemcially, a few extremely hydrophobic proteins are detected in the lipopigment storage material; these include subunit c of the mitochondrial ATP synthase and sphingolipid activator proteins (SAPs or saposins) A and D [39][40][41][42][43][44][45].…”

“…By late second to early third decades, the patients are nonambulatory. This is followed by death, usually within a year [39,40,[79][80][81][82][83][84][85][86][87][88][89]. At autopsy, the brain is small with a moderate to severe decrease in weight and grey and white matter atrophy.…”

“…Subsequently, there is extensive loss of retinal neurons in all layers. On the other hand, lipopigment-containing neurons, gliotic astrocytes, and melanin-containing macrophages abound [39,40]. Ultrastructural examination shows FPPs that may occur alone or in association with CLPs and/or RLPs and rarely GRODs [46][47][48][49][50][51][52][53].…”