Argininosuccinic aciduria: prenatal studies in a family at risk.

We have monitored two successive pregnancies in a family which we found to be at risk for argininosuccinic aciduria. We measured argininosuccinic acid (ASA) concentrations in amniotic fluid and utilized an indirect assay of ASA lyase activity in cultured amniotic fluid cells. The assay procedure is based on the uptake of 14C from [14C]citrulline and of [3H]leucine into protein. ASA was easily measured in amniotic fluid from the first fetus at risk, whereas none was detectable in control fluids. Amniotic fluid cells cultured from this fetus had only 5.5% of control ASA lyase activity. The pregnancy was terminated, and hepatic ASA lyase activity in the fetus was shown to be about 1.3% of control values. In addition, eight fetal tissues were analyzed for ASA, and all had significant accumulation. ASA was not detected in amniotic fluid from the second fetus at risk, and ASA lyase activity in cultured cells was 80% of control activity. Enzymatic analysis of erythrocyte lysate confirmed the diagnosis of an unaffected child (ASA lyase = 46% of control) and indicated heterozygosity. Thus, we provide further evidence that argininosuccinic aciduria can be diagnosed successfully in utero by indirect assay of ASA lyase activity in cultured amniotic fluid cells. In addition, high amniotic fluid ASA concentrations provide strong adjunctive evidence for such a prenatal determination, and may prove to be sufficient for diagnosis.     

DNA studies in a family with Duchenne muscular dystrophy and a deletion at Xp21.

We have performed Southern blot analysis on a large, four-generation kindred with Duchenne muscular dystrophy (DMD). Probes 754 (DXS 84), pERT87-1, pERT87-8, pERT87-15 (DXS164), and pXJ-1.1 did not hybridize to digested genomic DNA of affected males. Obligate-carrier mothers and unaffected brothers showed signals of a single X-chromosome copy intensity, and suspected noncarrier sisters demonstrated either a single band of two-copy intensity or informative polymorphisms. Uniform hybridization was seen with probes C7 (DXS28) and D2 (DXS43), which map distal to the DMD locus, and with OTC, which maps proximally. This deletion was present in six affected individuals and has been transmitted through 3 generations to date. On high-resolution chromosome analysis, a deletion within band Xp21 was consistently observed in one affected male studied and in one of the two X chromosomes in obligate carriers. This large molecular and cytogenetically visible deletion in affected DMD individuals without glycerol kinase deficiency, chronic granulomatous disease, retinitis pigmentosa (RP), or ornithine transcarbamylase deficiency is a very rare finding and should prove useful in specifically cloning additional probes within and flanking the DMD locus.     

Main results of recent Hungarian family planning studies.

The demographic situation in Hungary is analyzed by presenting results of 5 different surveys on family planning carried out between 1958-1974. During those 16 years the practice of planning the number of children desired grew. In 1958 only 63 out of 100 women planned the number of children at marriage, and in 1974 98% gave an affirmative reply. The number of children planned by women declined from 2.25 in 1958 to 2.05 in 1966, and then increased to 2.19 in 1974. More and more childless married women want to give birth to a child. In early studies, 66-67% desired a child, and in 1974 83% desired a child. The idea of a family size with 2 children has become the rule in Hungary. In 1958 only 76% of the women used birth control; by 1966 the percentage was 84. 37% in 1958, 44% in 1966, and 26% in 1969 used both contraception and induced abortion. By 1972, 42% of the women interviewed had had an abortion. The use of contraception has increased considerably from 58% in 1958 to 75% in 1974. In 1974, 36% of the women using contraception were taking oral pills and only 7% were using the IUD.     

Main results of recent Hungarian family planning studies.

The Hungarian Central Statistical Office has carried out five different sample surveys in the last fifteen years for investigating more closely questions of fertility, family planning and birth control. The study summarizes the main findings. Some of these surveys applied retrospective methods to investigate fertility, family planning and birth control bahaviour of females in the past. Surveys of another type tried to reveal in perspective manner, with longitudinal observation of the couples, changes which took place in family planning and birth control ideas and practice. The main purpose of recent population policy measures was to ensure simple reproduction of the population. As a result of the measures taken in 1974 to increase the number of births the birth-rate went up significantly. This increase (30% as compared to 1973) appeared primarily for the second birth which constitutes 62% of the increment in births in 1974, 31% is accounted for by an 11% increase in the first births. The number of third births rose by 13% and their relative share remained 10%. The number of fourthand further births did not increase and their relative share decreased by 1%. Fertility data of 1974 show that the birth-rate increase was not in line with the intended aim, i.e. it was not the number of third births that increased. The net reproduction coefficient showing long-range growth of the population calculated with birth-rate of 1974, has developed favourably, it was over unity for the first time since 1958 (it was about 1.05). The birth-rate increased in 1974 in every age-group of females. The largest increase (19%) occurred for females 25-34 years old. Though it was 16% also for females under 24. According to a sample survey investigating the number of intended children by married females under 35 it did not increase as compared to data of previous surveys of similiar character. The differences is that the proportion of those who wished to have two children increased, while of those who wished to have one or three and more children decreased. The study deals also with changes in the relative shares of intended children by females under 35 who are now to be married. In the concluding part of the study the femeles' attitude to birth control and changes in this field are discussed.     

Aspirin exposure during the first 20 weeks of gestation and IQ at four years of age

The relationship between maternal aspirin use during the first 20 weeks of pregnancy and the child's IQ at 4 years of age was investigated in 19,226 pregnancies occurring from 1959 to 1966 in the Collaborative Perinatal Project. The mean IQ of children exposed to aspirin was 98.3, which was 2.1 points higher (95% confidence interval = 1.7, 2.6; P less than 0.0001) than that of unexposed children. Adjustment for multiple social, demographic, and other confounders reduced this difference to less than one point in favor of the aspirin exposed group, although statistical significance remained. Total days of exposure was used as an index of dose, and no dose-response relationship between aspirin use and IQ was found. The effect of prenatal aspirin exposure did not vary by infant sex. It is concluded that an adverse effect of aspirin exposure on IQ is unlikely.     

The first 10 years of the dialysis-transplantation program at The Hospital for Sick Children,Toronto. 1: Predialysis and dialysis.

Renal dialysis and transplantation have been used for many years for adults with kidney failure but only recently for children. In May 1967 a renal-dialysis-transplantation program was established at The Hospital for Sick Children, Toronto for patients aged 6 to 18 years living within 240 km of Toronto. In 1973, children aged 1 to 5 years began to be accepted into the program, and by August 1977, 90 children (mean age 11 years) from all parts of Canada had been admitted to the program. The creation of vascular access in very small patients is difficult; the most successful types of access have been central shunts (established above the knee or the elbow) and bovine grafts. Specially made dialysis equipment is necessary for young patients. Young children should only be accepted in a dialysis-transplantation program that has a medical staff expert in meeting the specific needs of such children.     

Continuous intrauterine copper contraception for 3 years: comparison of replacement at 2 years with continuation of use.

A total of 1245 women had a copper 7 intrauterine contraceptive device (IUD) inserted in 1971-3 were followed up for three years (22 761-5 women months of use). After 24 months 483 women elected to continue with the same copper 7 (continuation group), and 183 had their copper 7 replaced with a new one (replacement group). The subsequent pregnancy and expulsion rates were both significantly lower in the replacement group. The higher pregnancy rate among the women who continued to use their copper 7 device for a third year suggests that although the copper is still there, it is not available for contraceptive action. Replacing the device at 24 months did not seem to cause again the problems that usually occur in the first six months of IUD use.     

Reproduction in Brahman cows calving for the first time at two or three years of age

A comparison of the subsequent reproduction of heifers that calved for the first time at 2 vs. 3 yr of age was conducted on a purebred Brahman herd from 1971 to 1978 in central Florida. Pregnancy rate, birth rate and weaning rate were obtained on 1,612 animals. Sire of the cow had a significant effect on all three reproduction traits, indicating possible genetic differences in these important traits. Age at first calving (either 2 or 3 yr) had no significant effect on overall reproduction rates; however, subsequent pregnancy and weaning rate was 4% higher in females calving first at 2 yr of age. Thirty-eight percent of the females that became pregnant at 15 to 17 mo of age, weighed 650 to 700 lbs. These heifers had been born early in the previous calving season. It is suggested that Brahmans can be selected to calve at 2 yr of age if good nutrition and management are provided.     

Genetic linkage studies with cleft lip and palate: report of two family studies

Genetic linkage studies are reported on two families with cleft lip +/- cleft palate. For the first family (LP01) the etiology of the clefting is unknown, and the linkage analyses were done assuming both autosomal dominant and autosomal recessive inheritance. Close linkage is rejected with the Duffy blood group under the dominant model and with four loci (Duffy, Kidd, and ABO blood groups and haptoglobin) under the recessive model. The second family (LP02) is a Mexican-American family segregating the van der Woude syndrome with lip pits. The linkage analyses for this autosomal dominant trait excluded close linkage with seven genetic markers, including three on chromosome one. The maximum lod scores were 0.6 with BF (chromosome 6) and 0.4 with the P blood group, which is not yet mapped.