Amniotic fluid amino acids in maternal phenylketonuria

544

(‘LINIC.4

CHIMICA

ACTA

ccA4920 Amniotic

fluid amino acids in maternal phenylketonuria*

Several

recent

studies

have shown that

untreated

maternal

phenylketonuria

(PKU) is associated not only with mental retardation

in the offspring (in a recent survey 65 out of 68 such children were retarded)‘, but also with microcephaly, cardiac, defects, epilepsy, strabismus and various skeletal and other anomalies. As Yu and O’Halloran have pointed out I, the high incidence of severe congenital anomalies and spontaneous abortions in this condition, indicates the importance of early intrauterine influences. For this reason we should like to report on the amino acid composition of amniotic fluid in two women with phenylketonuria. PATIESTS ANI) METHODS The first patient (case I) was aged 21. The diagnosis of PKU was first established as a result of urine testing during antenatal care. She is of low average intelligence (she refused formal IQ testing) and has never been on any dietary treatment. She underwent therapeutic abortion at 10 weeks gestation (according to her I,.M.P.) at which time her serum phenylalanine level was elevated (14.10 mg/Ioo ml, compared with normal values of less than 1.50 mg/Ioo ml). The fetus weighed 77 g, the crowm rump length was IO cm, it appeared normal on macroscopic examination but urlfortunately further studies on the material were not possible. The second patient (case 2) was aged 24. She has an IQ of 55 and was ne\.c’r treated with diet before the present pregnancy. She concealed the pregnancy until about the 20th week of gestation at which time therapeutic abortion was declined. LTntil term she was treated with a combination of nminogran and a restricted phenylalanine diet Her serum phenylalanine level was maintained between 3 and 12 mg //IOO ml (average 7 mg/roo ml) throughout pregnanqr. She was delivered at term in r(r~o of a male fetus which showed no congenital anomalies and in particular no pllen!.lketonuria and no abnormalities of skull or skeleton on radiography or of eye or heart. He is no\v 15 months old and is developing normally. The mother’s serum phcn!.lalanine level was z4 mg/Ioo ml three months after delivery. Tllis patient has been described in detail elsewhere’. Aliquots of amniotic fluid were deproteinised by ultrafiltration and then sub jetted to ion-exchange chromatography (Technicon ~ Model NCI) as described previously3. Sormal values for the amino acid content of amniotic fluid were obtained from specimens of fluid from healthy women at the time of delivery or therapeutic abortion”. Previous studies have shown that the amino acid content of amniotic fluid depends on the period of gestation3 and for this reason comparisons were made bctween specimens obtained at roughly the same stage of gestation. RESULTS The amino acid content of amniotic fluid specimens obtained from the two mothers with PKU and in normal controls of comparable gestation are given in Table 1, * This

work

was supportd

CliM. ChiWl. .dCla, 37 (I);‘)

by a rcscarch .j+_+--_j4b

pmt

iroll

t11c sccretarT_

of state

Ior Scotla11tl.

BRIEF

NOTES

The total amounts

545 of amino acids, including

tyrosine,

were normal in both cases but

whereas there was a slightly raised level of phenylalanine in case z (the specimen was contaminated with maternal blood which might account for this result) the amount of phenylalanine in case I was considerably elevated. No other differences in the amino acid content of these two fluids were observed when compared with controls of comparable gestation. In neither of these cases were there any peaks which could not be identified.

COhIiMEh’TS

In the present

study the phenylalanine

considerably elevated trolled PKU, but was who was subsequently The source of the

at the time only slightly delivered of amino acids

level of amniotic

fluid was found to be

of therapeutic abortion in a mother with unconraised at term in a mother with controlled PKF a normal healthy child. in amniotic fluid in the first trimester of pregnant)

is not clear but may well be of maternal origin. However, from about the rzth week of gestation fetal urine contributes to the formation of amniotic fluid and may then be the major source of the amino acids in amniotic fluid (including- phenylalanine)‘. Further, it has recently been shown that from at least the rrth week of gestation phenylalanine hydroxylase and dihydropteridine reductase as well as natural cofactor are present in human fetal livers. It is possible however, that the immature enzyme system of the fetus may be compromised by high levels of phenylalanine derived from the maternal circulation. This is perhaps especially likely to happen if the fetus is heteroz!rgous for PKU, as is the case when the mother is affected with this disorder. From the high level of phenylalanine in the amniotic fluid observed in case I, one might presume that the child would have been affected in some way. It is suggested that more cases should be studied in this way since amniotic fluid levels of phenylalanine may prove a useful guide to fetal prognosis in this condition. Whether PKC itself can be diagnosed in utcro in early pregnancy amniotic fluid is not known.

from the amino acid analysis

of

\Ve should like to acknowledge the excellent technical assistance of Mr. D. Burt, and thank Dr. Marion C. Miller and Dr. A. H. C. \!‘alker for obtaining specimens of amniotic fluid from the two patients.

546 University De$t. Human Genetics, Western General Hospital, Edinburgh. University Dept. Child Lift? and Healtlz, Royal Hosfiital jar Sick Children, Edinburgh. University Dept. Medical Genetics, MamAester Royal In$wlagt,, Xanclzcstev (U.K.)

Received

November

II,

1971