|
|
| (One intermediate revision by the same user not shown) |
| Line 2: |
Line 2: |
| {{Lesch-Nyhan syndrome}} | | {{Lesch-Nyhan syndrome}} |
| {{CMG}}; {{AE}} {{AN}} | | {{CMG}}; {{AE}} {{AN}} |
| | |
| | {{PleaseHelp}} |
|
| |
|
| ==Overview== | | ==Overview== |
| When an affected individual has fully developed the three clinical elements of uric acid overproduction which is neurologic dysfunction, and cognitive and behavioral disturbances, diagnosis of LNS is easily made. Difficulties of diagnosis are abundant in the early stages when the three features are not yet obvious. Suspicion often comes about when the developmental delay of the individual is associated with [[hyperuricemia]].
| |
|
| |
|
| ==Laboratory Findings== | | ==Laboratory Findings== |
| ===Blood tests===
| |
| *[[Hyperuricemia]]
| |
| *Increase in [[serum creatinine]] levels
| |
| *Increased [[uric acid]] levels
| |
| *[[Megaloblastic anemia]]:
| |
| **Raised [[MCV]]
| |
| **[[Macrocytosis]]
| |
| **[[Vitamin B12]], [[Folate]] and [[serum iron]] levels are normal
| |
| *[[Urate]]: [[creatinine]] ratio is elevated
| |
| **good indicator of acid overproduction
| |
| **For children under 10 years of age, the ratio is usually more than 2
| |
|
| |
| ===Urinalysis===
| |
| *[[Microhematuria]] or frank [[hematuria]]
| |
| *24 hour [[urate]] excretion of more than 20 mg/kg is also typical but is not [[diagnosis|diagnostic]].
| |
|
| |
| ===Biochemical Testing===
| |
| *Biochemical analyses, although not routinely performed, on hair bulbs from at risk women have had a small number of both [[Type I and type II errors|false positive]] and [[false negative]] outcomes.
| |
| *If only a suspected carrier female is available for [[HGPRT1]] [[mutation]] testing, it is appropriate to grow her [[lymphocytes]] in 6-thioguanine (a [[purine|purine analogue]]), which allows only [[HGPRT]]-deficient cells to survive.
| |
| *A mutant frequency of 0.5-5.0 x 10-2 is found in carrier females, while a non-carrier female has a frequency of 1-20 x 10-6. This frequency is usually diagnostic by itself.
| |
| *Molecular genetic testing is the most effective method of testing, as [[HGPRT1]] is the only gene known to be associated with LNS. *Individuals who display the full Lesch-Nyhan [[phenotype]] all have mutations in the [[HGPRT1]] gene. Sequence analysis of [[mRNA]] is available clinically and can be utilized in order to detect [[HGPRT1]] mutations in males affected with Lesch-Nyhan syndrome. *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 [[HGPRT1]] 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.
| |
|
| |
| ===Other tests===
| |
| *Activity of [[HGPRT]] enzyme [[fibroblasts]]s or [[lymphoblast]]s that is less than 1.5% of normal enzyme activity confirms the diagnosis of Lesch-Nyhan syndrome.
| |
|
| |
|
| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
| | |
| | [[Category:Pediatrics]] |
| | [[Category:Endocrinology]] |
|
| |
|
| {{WH}} | | {{WH}} |
| {{WS}} | | {{WS}} |