The HPRT1 gene encodes the production of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). This enzyme plays a controlling role in purine metabolism. Virtually complete deficiency of HPRT (residual activity less than 1.5%) is diagnostic of classic LNS in males. HPRT activity of 1.5% to 8% is associated with a neurological variant of LNS, with uric acid overproduction and neurologic disability that varies from minor clumsiness to debilitating extrapyramidal and pyramidal motor dysfunction. Partial HPRT deficiency (residual enzyme activity of at least 8%) is associated with Kelley-Seegmiller syndrome (KSS). Renal stones, uric acid nephropathy, and renal obstruction are often the presenting symptoms of Kelley-Seegmiller syndrome, but rarely of LNS. While LNS is characterized by abnormal metabolic and neurologic manifestations, KSS is usually associated only with the clinical manifestations of excessive purine production. Measurement of HPRT enzyme activity for carrier detection in females is technically demanding and not widely used.
Sequence analysis of the HPRT1 gene in males with full LNS phenotype has been shown to identify the majority of mutations (218 mutations identified in 271 families in one study). Twenty-one to twenty-four percent of mutations have been shown to be large deletions. Each family generally has a unique mutation. The prevalence of LNS is approximately 1:380,000. It appears to occur in all populations that have been studied, and with relatively equal frequency.
For patients with suspected LNS, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
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- Confirmation of a clinical/biochemical diagnosis of LNS in an individual in whom sequencing analysis was negative
- Carrier testing in adult females with a family history of LNS in whom sequencing analysis was negative
Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
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Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.