2,8-Dihydroxyadeninuria in leeland
THRÖSTURLAXDAL M.D., Specialist in Pediatrics, Sjukrahus Reykjavikur, Iceland.
Renal stones in European children have been
considered rather uncommon. Only aminority (l
O-
20
%)
are due to ametabolicdefect, the best known
being idiopathichypercalciuria, cystinuriaanduric
acid crystalluria
(1).
The last mentioned has fre–
quently been confused with another less known
disturbance in purine metabolism, namely 2,8-
dihydroxyadeninuria (l ,2).
In 1983, the chief laboratory technician at St.
Joseph 'sHospital,Landakoti,Reykjavik, reported
the finding ofround,redbrown crystals in the urine
of a
6
year old girl, who had been hospitalized
becauseofrecurrent urinary tract infections (Fig. l
a and b). The crystals were analyzed by gas chro–
matography/mass spectrometry and consisred of
2,8-dihydroxyadenine (2,8-DHA) (3,4).
Fig. l a,b
The friab/e round
2
,8-dihydroxyadenine crystals with
darker outline show spicules radiating from the center.
The usual red-brownish color canfade towards yellow–
brownish. Original magnification x 500
KliniskKemi
i
Norden
2,
1996
This first case of 2,8-dihydroxyadeninuria in
leelandwas diagnosed 12years ago, but since then
15 additional cases havebeen found, almost halfof
them children.
Themetabolic defect
This congenital disturbance ofpurinemetabolism
iseithercaJledadenine-phospho-ribosyl-transferase
(APRT)deficiency by referral to its nature, or 2,8-
dihydroxyadeninuria, according to itsconsequence.
It is ahereditarydisorder,inherited inanautosomal
recessivemanner and characterized by deficiency
of the enzymeAPRT inall tissuecells. TheAPRT
deficiencymaybestbe identifiedbymeasuring the
APRT activity in lyzed erythrocytes (2).
A simplified diagram (Fig. 2) ofpurinemetabo–
lism shows, that adenine can not be converted to
adenosine monophosphate (adenylic acid) in the
PATHWAYS OF PURINE METABOLISM
I?_:T[+===rr~TI
Adenine
Adenosine
inoalne-Hypoxanthine
r----
---,
8-Hydroxyad::::--, XANTHINE OXIDASE
r····
Xanthine
J-----------
--------l
2,8 Dlhydroxyadenlne
Urlc acld
APRT : Adenine-phosphoribosyltransferasa
HGPRT: Hypoxanthine-guanine-phoaphorlboayltransferase
AMP : Adenoslne monophosphate
IMP
: lnosine monophosphate
PAPP : 5' - phosphorlbosyl pyrophoaphate
Fig.
2
A simplified diagram ofpurinemetabolism.
absence of APRT. The accumulated adenine is
mostly oxidized by xanthine oxidase via the 8-
hydroxyadenine intermediate to thepoorly soluble
2,8-dihydroxyadenine (2,8-DHA),whichhasdirect
nephrotoxiceffect, asweilasformingkidneystones.
Fortunately this enzymedeficiencyonlyaffects the
urinary tract, incontrasttodeficiencyoftheanalogue
enzyme, hypoxanthine-guanine-phospho-ribosyl–
transferase (HGPRT), which besides eausing uric
acid crystalluria and stones, leads to irreversible
53
