The de novo pathway is stimulated due to an excess of PRPP (5-phospho-D-ribosyl-1-pyrophosphate or simply phosphoribosyl-pyrophosphate).It was previously unclear whether the neurological abnormalities in LNS were due to uric acid neurotoxicity or to a relative shortage in "new" purine nucleotides during essential synthesis steps. Genetic mutations affecting the enzymes of the de novo synthesis pathway may possibly contribute to the disease, although these are rare or unknown. Uric acid has been suggested as a possible cause of neurotoxicity but this is unproven.Importantly, evidence suggests that one or more lesions in striatal dopaminergic pathways may be central to the neurological deficits, especially the choreoathetoid dyskinesia and self-mutilation. 6-hydroxydopamine toxicity in rodents may be a useful animal model for the syndrome, although this is not proven. However, the link between dopamine and purine synthesis is a nucleotide called guanosine triphosphate or GTP. The first step of dopamine synthesis is GTP cyclohydrolase, and significantly a deficiency of this step produces a syndrome that has a neuropathology similar to LNS. Thus a lack of HGPRT may produce a nucleotide deficiency (specifically: GTP deficiency) disorder, resulting in dopamine deficiency.Another animal model for LNS has been proposed to arise from oxidative damage, caused by the hyperuricemia accompanying LNS. This is based on the theory that uric acid is a powerful reducing agent and likely an important human antioxidant, in high concentration in blood.
Techniques such as RT-PCR, multiplex genomic PCR, and sequence analysis (cDNA and genomic DNA), used for the diagnosis of genetic diseases, are performed on a research basis. If RT-PCR tests result in cDNA showing the absence of an entire exon or exons, then multiplex genomic PCR testing is performed. Multiplex genomic PCR testing amplifies the nine exons of the HPRT1 gene as eight PCR products. If the exon in question is deleted, the corresponding band will be missing from the multiplex PCR. However, if the exon is present, the exon is sequenced to identify the mutation, therefore causing exclusion of the exon from cDNA. If no cDNA is created by RT-PCR, then multiplex PCR is performed on the notion that most or all of the gene is obliterated. Treatment
Treatment for LNS is symptomatic. Gout can be treated with allopurinol to control excessive amounts of uric acid. Kidney stones may be treated with lithotripsy, a technique for breaking up kidney stones using shock waves or laser beams. There is no standard treatment for the neurological symptoms of LNS. Some may be relieved with the drugs carbidopa/levodopa, diazepam, phenobarbital, or haloperidol.It is essential that the overproduction of uric acid be controlled in order to reduce the risk of nephropathy, nephrolithiasis, and gouty arthritis. The drug allopurinol is utilized to stop the conversion of oxypurines into uric acid, and prevent the development of subsequent arthritic tophi (produced after having chronic gout), kidney stones, and nephropathy, the resulting kidney disease.