Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset. Symptoms and signs
Sandhoff disease symptoms are clinically indeterminable from Tay–Sachs disease. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at this early age. The first signs of symptoms begin before 6 months of age and the parents’ notice when the child begins regressing in their development. If the children had the ability to sit up by themselves or crawl they will lose this ability. This is caused by a slow deterioration of the muscles in the child’s body from the buildup of GM2 gangliosides. Since the body is unable to create the enzymes it needs within the central nervous system, it is unable to attach to these gangliosides to break them apart and make them non-toxic.
Primitive neuroectodermal tumor is a malignant (cancerous) neural crest tumor. It is a rare tumor, usually occurring in children and young adults under 25 years of age. The overall 5 year survival rate is about 53%.It gets its name because the majority of the cells in the tumor are derived from neuroectoderm, but have not developed and differentiated in the way a normal neuron would, and so the cells appear "primitive".PNET belongs to the Ewing family of tumors. Genetics
Using gene transfer of SV40 large T-antigen in neuronal precursor cells of rats, a brain tumor model was established. The PNETs were histologically indistinguishable from the human counterparts and have been used to identify new genes involved in human brain tumor carcinogenesis. The model was used to confirm p53 as one of the genes involved in human medulloblastomas, but since only about 10% of the human tumors showed mutations in that gene, the model can be used to identify the other binding partners of SV40 Large T- antigen, other than p53. Diagnosis
Classification
It is classified into two types, based on location in the body: peripheral PNET and CNS PNET. Peripheral PNET
The peripheral PNET (pPNET) is now thought to be virtually identical to Ewing sarcoma:
"Current evidence indicates that both Ewings sarcoma and PNET have a similar neural phenotype and, because they share an identical chromosome translocation, they should be viewed as the same tumor, differing only in their degree of neural differentiation.