quinta-feira, 11 de julho de 2013

Kelley-Seegmiller syndrome

The Kelley-Seegmiller syndrome (KSS) is a milder form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) (see this term), hereditary pathology of purine metabolism, and is associated with overproduction of uric acid (UAA) leading to urolithiasis and drop early.

The exact prevalence is unknown, but probably underestimated because of the fault diagnosis. KSS may represent about 15% of patients with HPRT deficiency. The age of onset is usually in childhood, but can also be an adult (30 years). The males are generally affected and heterozygous female are carriers (usually asymptomatic). Patients are normal at birth.

The first manifestation is the presence of crystal-colored orange in diapers. Urolithiasis, uric acid nephropathy, urinary tract infections and renal obstruction are often the presenting symptoms. Gout can appear after puberty with acute arthritis or tophi. In contrast to the Lesch-Nyhan syndrome (LNS; see this term), dystonia can be mild or even be absent. Patients have normal intelligence associated with varying degrees of attention deficit. The compulsive self-injurious behavior is absent.

The disease is caused by partial deficiency caused by mutations in the HPRT gene HPRT1 (Xq26). Inheritance is X-linked recessive. The SAU may be caused by impaired recycling of purine bases increased synthesis of purine nucleotides causing hyperuricemia, which increases the risk of precipitation of crystals forming tophi AU tissue in joints leading to inflammatory arthritis and gouty arthritis, and excretion AU causing renal urolithiasis.
Diagnosis and Treatment
The diagnosis may be suspected when there nephrolithiasis and / or obstructive nephropathy and is based on biochemical, enzymatic and molecular studies. Hyperuricemia and the SAU are detectable in serum and urine. The plasma levels and urinary excretion of urate, hypoxanthine, and to a lesser extent, xanthine are high. The hemolyzed in HPRT activity ranges from 0.5% to 10%.

The differential diagnosis includes glucose-6-phosphate dehydrogenase, the Lesch-Nyhan and overactivity of fosforribosilpirofosfato synthetase (PRPP) (see these terms).

The prenatal diagnosis is not usually needed.

The SAU, nephrolithiasis, gouty arthritis and tophi can be treated with allopurinol, alkalinization of urine (bicarbonate or sodium citrate) and abundant hydration. Doses should be carefully adjusted to avoid xanthine lithiasis.


With proper treatment, renal function remains stable and patients have a normal life expectancy.

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