damage of the central nervous system (Lesch
Nyhan'ssyndrome) (2). Except for theexcretionof
adenine and its metabolites, no other biochemical
abnormalities have been found so far. The pro–
ductian andexcretion ofotherpurines are conside–
rednormal, indicating thatAPRT isnot vital for the
overall control of purinemetabolism in humans.
The 2,8-DHA crystals/stones
2,8-DHA is 50 timesless soluble thanuric acid and
its salubility in urine is only 2-6 mg/L. However,
some individuals have shown the ability to
supersaturate the 2,8-DHA in vivo, which might
explainwhy they can stay asymptomatic for many
years,while others form stones at an ear!y age (2).
In themicroscope, the2,8-DHAcrystalsaremost
often easily identifiedas round, concentric and red–
brownish in color, sometimes fading towards
yellow-brownish. Aftercentrifugationoftheurine,
the crystals are macroscopically distinguished as
red-brownish sediment, which quickly looses the
brownish color,when it dries up and becomes pale
grayish or beige-colored.
If
2,8-DHA stones are
formed, they are quite rough and easily breakable
(Fig 3), in contrast to uric acid stones, which are
hard, yellow with smooth surface and crush with
Fig. 3Macroscopic2 ,8-DHA stoneappearance: grayor
beige when dry, rough and breakable.
difficulty. Nevertheless the radiolucent 2,8-DHA
stones are frequently misdiagnosed as uric acid
stones. For such closely related compounds, one
must resort to specialized differentiatingmethods,
like gas chromatography/mass spectrometry,
X–
ray crystallography or ultraviolet/infrared
spectrophotometry, whichhas becomeourmethod
54
ULTRAVIOLET SPECTRUM
2,8-DHA
PT. 4
260 280 300 320 340
nm
Fig. 4 The ultravia/et pattern shows a goodCOITelation
inwave length ofmaximal absorption spectrum through
differentpH leve/s,betweenpure2,8-DHAon the lejtand
deposits ofurine crystals on the right.
INFRARED SPECTRUM
l
WAVENUMBER
Fig. 5 The infrared spectrum shows almost identical
pattern between the patient'
s
urine crystals above and
2,8 DHA below.
of choice (Figs. 4 and 5). The 2,8-DHA stonesare
usually only 96-98% pure, the rest being adenine
and uric acid, with a trace of calcium (2)
Diagnosis
The diagnosis of2,8-dihydroxyadeninuria is esta–
blishedby the specificanalysesofcrystals
or
stones
mentioned above, and finally confirmed by direct
measurement of the APRT enzyme activity in the
erythrocytes. TherangeofAPRTactivityofaffected
homozygotes is from undetectable to 1.0nmol/mg/
Hb/hr, while the mean of normal activity is 26
nmol/mg/Hb/hr. The heterozygotes have APRT
enzyme activity around 50% of normal (2).
Epidemiology - Prevalence
The APRT deficiency was first described in 1974
byCartier in Paris. Hereported a patient, who had
suffered from recurrent rena! stonesfrom2years of
age. For a Iong time they had been considereduric
acid stones, but finally, spectrophotometry revea–
led their true identity. Even then, autosomal
Klinisk Kemi
i
Norden 2. 1996
