Rare inborn error of purine metabolism that becomes
apparent between the ages of 3 and 6 months. Characterized by the presence
of orange crystal-like deposits (“orange sand”) in the diapers of infants
with the disorder. This is frequently the first symptom of Lesch-Nyhan
syndrome. Other clinical features include hematuria, urinary tract
infections, arthritis, choreoathetosis manifested by raising and lowering of
the shoulders, and facial grimacing. Hypotonia, hypertonia, hyperreflexia,
and spasticity have been reported. Megaloblastic anemia, self-mutilating
behavior, irritability, screaming, uncontrolled aggressiveness, and
compulsive actions complete the clinical presentation.
Hypoxanthine-Phosphoribosyl-Transferase Deficiency Disease; Complete
HGPRT Deficiency Disease; Kelley-Seegmiller Syndrome;
Genetically transmitted error of metabolism of purine
Estimated at 1:380,000 live births in the United States;
almost exclusively males, although a few females are reported
(heterozygotes, mild form of the disease).
X-linked (Xq26-Xq27) recessive disorder caused
by a mutation in the gene coding for the enzyme hypoxanthine
phosphoribosyltransferase (HPRT). Different mutations have been described.
The mutation leads to total or partial loss of
function of HPRT, which normally catalyzes the conversion of hypoxanthine
and guanine to inosinic and guanylic acid, a reaction that allows reuse of
preformed purine bases resulting from cell turnover and catabolism. The
absence of this reaction results in overproduction of uric acid and leads to
hyperuricemia and uricosuria and thus urate nephropathy, urinary tract
calculi, and gout. The neurologic features of the syndrome (choreoathetosis,
self-mutilation, spasticity) are caused by abnormalities in brain
neurotransmitters, mainly decreased dopaminergic activity in the basal
ganglia. Treatment with inhibitors of xanthine oxydase (allopurinol 10
mg/kg/day, maximum 800 mg/day) can control hyperuricemia but does not
prevent the effect on neurologic system. Poor prognosis (few patients live
beyond age 40 years).
Patients are normal at birth; onset after a few months.
Diagnosis can be clinically evocated by the observation of orange crystals
in the diapers or crystalluria with obstruction of the urinary tract.
Psychomotor retardation appears quickly (delay in acquisition of sitting and
head support), followed by spasticity and athetoid movements.
Self-mutilation is characteristic and can start as soon as teeth are
present. Enzyme and molecular studies confirm diagnosis.
Boys only are affected; the first symptom is
often the presence of orange-colored crystal-like deposits (“orange sand”)
of urates in the diapers of affected infants.
Total Deficit in HPRT: Manifests during the first year of life with motor development delays.
Thereafter, choreoathetotic movements with dysphagia and dysarthria; later,
axial hypotonia and limb spasticity. Compulsive self-mutilation (biting of
lips, fingers, and hands) and aggressive behavior usually appear between
ages 2 and 4 years, Nephrolithiasis and gouty arthritis occur if no
allopurinol treatment is given. Mental retardation is present, but the
severity is difficult to determine because IQ testing is problematic.
Partial Deficit in HPRT: The child presents with juvenile gout with nephrolithiasis; there is no
self-mutilation and the neurologic signs are ...