recessive inheritance was demonstrated by
measuring theAPRT activity in erythrocytes from
close relatives
(S).
The next 3cases, also children,
were then described by Ann Simmonds and
coworkers at the Purine Research Laboratories at
Guy'sHospital in London (6,7).
The prevalence of heterozygosity for APRT
deficiency in different Caucasian populations has
been estimated to be 0,4-1,1%. This would sugg–
est homozygosity of the order of l in
2SO.OOO
to l
in
33.000 of total population. Until now 16 homo–
zygotes have been found
in
the leelandie popula–
tion (266.000 inhabitants), which make the pre–
valence l in 16.000. According to Dr Simmonds,
alittlemore than l00casesofAPRT*Qo deficiency
areknown in thewholeworld. Theycome from 19
countries and almost two-thirds are children and
70% of the patients are found in three countries,
Japan
(3S
patients),France (21patients) and leeland
(16 patients) (8.9). To the best ofour knowledge,
no patient has yet been reported from the other
Nordie countries.
The leelandie material
Ourpatientgroupconsistsof8males and8females
and 6 of themwere still in childhood at diagnosis.
The distribution in sex, age, year ofdiagnosis and
main clinical symptoms are outlined in Table l.
Clinical symptomswereextremelyvariableand six
of the patients were entirely asymptomatic, two
adults and three children,
t
wo of whom were dia–
gnosed because of brownish spotsin their diapers.
The 3 asymptomatic children, patients #4, #6 and
#8 were detected "by coincidence", by urine
microscopy. All the other asymptomatic subjects
reported in the literature have been found when
investigating family members of known sympto–
matic patients. The other patients had urinary tract
infections, dysuria, hematuria, rena! colic and
nephrolithiasis and one patient had severe renal
damage requiring nephrectomy. lt was an interes–
ting and unexplained finding that 12 of the 16
patients had red hair (*mark behind their initials),
compared to
4-S%
in thegeneral leelandie popula–
tion.
Aside from 3 pairs of siblings, (patients #9 and
#11; #10 and #12;
#S
#14 and #lS), our patients
seemed unrelated. Purther inquiries done by the
Genetical Committee of the University of leeland
revealed that seven of the patients proved to be
moreor less inteiTelated through4ancestors, living
in the southem and south-eastem part of leeland,
approximately 200 years ago (some 5-7 genera–
tions ago) (Fig.6). Each of the 4 ancestors re–
presented 2-3 of the patients and 5 patients could
trace their family tree back to 2 or 3 of the 4
ancestors,with theexceptionofpatient#4. Frequent
interfamilymaiTiages are noticeable. Three other
patients showed even closer relationship, through
great-grandparents and great-great grandparents,
who came from the nor1hern and western part of
leeland during the last century (fig. 7). At this
momentwehaveneitherbeen able toconnect these
2 extended grand families, nor to tie the 2 sets of
brothers to the other cases.
Genetics
The gene for human APRT has
been mapped to the Iong arm of
PATIENT
SEX
AGE
YEAR
CLI ICAL SYMPTOMS
chromosome 16. More recently,
the gene has been localized to po–
sition 16q24. Dr Amrik Sahota,
cuiTently working on molecular
genetics at lndiana University in
lndianapolis, sequenced theAPRT
gene from our patients and found
an identical missense mutation in
l
S
patients. The same mutation
wasdetected inapatientfromGreat
Britain, butnot in anyof4patients
from thecontinentofEurope. This
suggests that a founder effect is
Likely to be responsible for the
APRT deficiency in the leelandie
population
(lO).
#l
F
6
1983
Urinary infections; Renal colic
??
#2
M
46
1984
Hematuria; Dysuria; Rena) colic x2
#3
F
43
1985
Urinary inf.; Stones x3; Nephrectomy '71
#4
F
1986
o
#5
F
42
1990
Stones x3; Bilateral rena! op.l978
#6
M
0,5
1991
o
#7
M
28
1991
Rena! colic x2 and stones x2
#8
F
16
1991
o
#9
M
33
1991
Rena! stones x J
#JO
M
6
1992
Recurrent abdominalia. Colic ??
#Il
M
39
1992
o
#12
M
1992
o
#13
M
1,5
1995
Recurrent hematuria, abd. pain, ur.tr.inf.
#14
F
43
1995
Bilateral rena! stones
#15
F
33
1995
o
#16
F
45
1995
Rena! failure. Hypertensia an.
( *
signifies red hair )
Table l. Clinieal eharaeteristies ofthe leelandie patients.
KliniskKemi
i
Norden
l,
1996
ss
