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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