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Biomedical subjects

C Laberge

Publications and source records attributed to C Laberge.

At least 37 records · Page 2Linked to original sources
PubMed1987

The Hartnup phenotype: Mendelian transport disorder, multifactorial disease.

The Hartnup mutation affects an amino acid transport system of intestine and kidney used by a large group of neutral charge alpha-amino acids (six essential and several nonessential). We compared developmental outcomes and medical histories of 21 Hartnup subjects, identified through newborn screening, with those of 19 control sibs. We found no significant differences in means of growth percentiles and IQ scores between Hartnup and control groups (but all low academic performance scores were found in the Hartnup group, and various skin lesions occurred in five Hartnup subjects), no significant difference between means of the summed plasma values for amino acids affected by the Hartnup gene in Hartnup and control groups, two Hartnup subjects with clinical manifestations--impaired somatic growth and IQ in one, impaired growth and a "pellagrin" episode in the other--who had the lowest summed plasma amino acid values in the Hartnup group; the corresponding values for their sibs were the low outliers in the control group, and two tissue-specific forms of the Hartnup (transport) phenotype: renal and intestinal involvement (15 families) and renal involvement alone (one family), both forms having been inherited as autosomal recessives (the symptomatic probands had the usual form). Whereas deficient activity of the "Hartnup" transport system is monogenic, the associated plasma amino acid value (measured genotype) is polygenic. The latter describes the parameter of homeostasis and liability to disease. Cause of Hartnup disease is multifactorial.

Amino Acids↗
PubMed1986

Hereditary tyrosinemias (type I): a new vista on tyrosine toxicity and cancer.

Review of the literature of the past 40 years on tyrosine and its toxicity shows that no direct link between this aromatic amino acid and carcinogenesis has been well established. Ten years ago, studies of tyrosine toxicity in mice suggested the formation of an epoxide adduction product presumably derived from tyrosine by way of the liver microsomal detoxification system. Another study showed an increased frequency of hepatomas following long-term treatment with para-hydroxyphenyllactic acid, a tyrosine derivative occurring in the absence of p-hydroxyphenylpyruvate oxydase activity. Recently, studies on hereditary tyrosinemias (Type I) have indicated that the primary enzyme defect in these diseases is a deficiency of liver and renal fumarylacetoacetase. This results in an accumulation of natural alkylating derivatives of homogentisic acid such as maleyl- and fumarylacetoacetate in liver. Adduction of these compounds by glutathione is demonstrated by the presence of the mercapturic acid S-2-fumaryl-acetone-N-acetylcysteine in urine of patients. This adduct is also present in the urine of a number of heterozygote carriers after oral loads consisting of small quantities of homogentisic acid. In this report, we present the results of preliminary animal studies on the biochemical nature of the toxic effects of these tyrosine derivatives in these diseases along with preliminary data on the influence of fumarylacetone on protein synthesis in cultured eucaryotic cells. Fumarylacetone reacts as a natural alkylating agent and may, along with maleylacetoacetate, be responsible for the high incidence of late-onset hepatoma in the clinical chronic forms of hereditary tyrosinemias.

Amino Acid Metabolism, Inborn Errors↗
PubMed1986

Purification of mRNA coding for the enzyme deficient in hereditary tyrosinemia, fumarylacetoacetate hydrolase.

As a step towards the cloning of the gene for fumarylacetoacetate hydrolase (FAH), we have purified the FAH mRNA from rat liver by specific immunoadsorption of polysomes. The relative abundance of this mRNA has been estimated to be 0.14%. The major in vitro translation product of the purified mRNA preparation is specifically precipitated by a rabbit anti-rat FAH antiserum and it is, furthermore, undistinguishable by criteria of mass and charge from purified rat FAH.

Amino Acid Metabolism, Inborn Errors↗
PubMed1979

Blood thyroxine concentration is lower in low-birth-weight infants.

From out data bank, we analyzed results for thyroxine concentration in blood samples spotted on filter paper from different age groups (one to nine days postpartum) of our low-birth-weight and normal population. It was significantly lower in the low-birth-weight infants in almost all the age groups, and in both groups it significantly declined after postnatal day 5. The influence of weight is more important in the low-birth-weight population, but does not completely explain the smaller values. The results indicate that blood samples used in screening for congenital hypothyroidism in the neonate should be taken on postnatal days 3 to 5, and if a recall specimen is collected on days 5 to 9, one should expect the thyroxine concentration in the second specimen to be lower than in the first.

Aging↗
PubMed1978

Genetics and Medicine: an evolving relationship.

The rapid expansion of knowledge in human and medical genetics has revealed at least 6 percent average heterozygosity per structural gene locus, in excess of 2300 Mendelian (single gene) variants and several hundred chromosomal variants in man. This means that with the exception of monozygous twins, no two individuals are alike in their phenotype. Therefore, each person has a relative state of health, and genetic factors contribute significantly to disease. The ubiquity of genetic diversity requires the development of services for genetic screening, diagnosis, and counseling to prevent and treat a major portion of disease in modern society. Specific programs in Quebec and Canada illustrate how individuals and populations can be served by such services. Better education of citizens and health professionals in human genetics is essential for the further improvement of genetics services in society.

Blood Chemical Analysis↗
PubMed1978

Modification of a screening program for neonatal hypothyroidism.

From our experience in the screening of 212,000 newborn infants, we have devised a flow chart for processing T4 and TSH measurements obtained from initial filter paper blood spots. To date, all infants with thyroid dysfunction or TBG deficiency have been detected. Of the population screened, 1.84% require a spot TSH determination, and 1.1% require repeat determinations of T4.

Filtration↗
PubMed1976

Thyroid function in neonatal hypothyroidism.

Various aspects of the thyroid function have been measured in 28 cases of neonatal hypothyroidism detected by means of the Quebec Screening Program for Metabolic Diseases. In all instances the T4 value in the blood of filter paper spot was below 2 SD of the mean of the day, averaging 0.39 +/- 0.04 ng/40 mul (mean +/- SEM) of eluted blood. The T4 value of a second similar sample averaged 0.22 +/- 0.04 ng/mul of eluted blood; this value was significantly lower than the first one. The serum T4 concentration was decreased in all the infants, whereas three of them had a normal serum TSH concentration. At least three groups of patients could be identified: (1) patients with primary thyroid failure, (2) those with secondary or tertiary hypothyrodism, and (3) those with abnormal synthesis of thyroid hormone.

Female↗
PubMed1976

TSH measurements from blood spots on filter paper: a confirmatory screening test for neonatal hypothyroidism.

A sensitive radioimmunoassay for the measurement of TSH in the eluate of blood spotted on filter paper has been developed. The method is consistently sensitive to 0.1 to 0.25 muU of TSH and enables the detection of values equivalent to 6 to 15 muU/ml of serum. The measurement of TSH in the filter paper spot in all infants with low filter paper spot T4 has permitted rapid confirmation of 10 cases of neonatal hypothyroidism. However, cases of hypothalamic hypothyroidism with low or normal filter paper spot TSH concentrations would have been missed using only this method. Since these patients represent approximately 10% of our neonatal hypothyroid population, we do not recommend this method as a primary screening procedure, but rather as a confirmatory test which will accelerate the diagnosis and therefore the onset of therapy.

Filtration↗
PubMed1976

alpha1-Fetoprotein measurement in blood spotted on paper: discriminating test for hereditary tyrosinemia in neonatal mass screening.

We describe an electroimmunodiffusion technique for measuring alpha1-fetoprotein in blood spotted on chromatography paper. The system is being used as a complementary test in a neonatal mass-screening program for detection of inborn metabolic diseases in the Province of Quebec. In a series of 102 cases of neonatal hypertyrosinemia, the test has proven to be highly discriminative for hereditary tyrosinemia. It has permitted early detection of eight cases of this disease, including two that would have been missed by the previously used screening procedure, tyrosine measurement only. The test not only virtually eliminates the risk of misdiagnosis or missed diagnosis, but also permits earlier diagnosis of hereditary tyrosinemia and considerably reduces the follow-up work required for newborns with transitory tyrosinemia. The AFP test is simple, fast, practical, and inexpensive. Combined with tyrosine determination, it constitutes an optimal device for mass screening of hereditary tyrosinemia.

Amino Acid Metabolism, Inborn Errors↗
PubMed1976

Factors influencing results for thyroxine concentration in blood, as measured in paper filter spots in a screening program for neonatal hypothyroidism.

To reduce the number of false-positives in our screening program for neonatal hypothyroidism, we investigated the effect of age, body weight, and interval between sampling and analysis on results for filter paper spot thyroxine determination. The statistical analysis included an analysis of covariance. The age of the infant did not influence the results, the interval influenced them minimally, but weight did require a correction factor of about 0.16 ng/kg below the mean weight. This correction factor should reduce our false-positives from 0.75% to 0.60%. Furthermore, because all hypothyroid infants had results that fell more than 2.8 SD below the geometric mean, we intend to measure thyrotropin concentrations in the blood eluate of all the spots with a thyroxine concentration below that cut-off point.

Body Weight↗
PubMed1975

Neonatal hypertyrosinemia and evidence for deficiency of ascorbic acid in Arctic and subarctic peoples.

Hypertyrosinemia tyrosine concentration in whole blood greater than 0.42 mmol/l or 7.5 mg/dl is prevalent among lnuit newborn of the Canadian Eastern Arctic. The rate was 14.8 per 100 newborn between January 1970 and December 1972 (first survey period) and 6.2/100 between January 1973 and September 1974 (second survey period); the corresponding rates among Indian newborn of Nouveau Quebec were 2.6 and 2.2%. Among Anglo-Saxons the rate was less than 0.5% and in French Canada it commonly exceeded 0.94%. Serum concentrations of ascorbic acid were low (less than or equal to 0.25 mg/dl) in the pregnant and age-matched adult lnuit when measured by Nutrition Canada during the first survey period. The percentages of inuit children (up to 4 years old) and pregnant women at "high risk" for scurvy (serum concentration of ascorbic acid less than 0.2 mg/dl) were 14.8 and 47.1, respectively; the corresponding national percentages were 3.0 and 2.2, respectively. Deficiency of ascorbic acid in pregnant women is probably the cause of the unusual prevalence of neonatal hypertyrosinemia among the native Arctic and subarctic peoples because ascorbic acid is required to maintain optimal activity of p-hydroxyphenylpyruvic acid hydroxylase and to permit normal oxidation of tyrosine.

Adolescent↗
PubMed1975

Preliminary report on a mass screening program for neonatal hypothyroidism.

We have recently developed an immunoassay that can measure thyroxine rapidly and accurately in the eluate of 40 mul of dried blood spotted on filter paper at the fifth day of life. The method is completely automated and by using the samples received by the Central Laboratory of the Quebec Network for Genetic Medicine and their follow-up facilities, we are now screening every newborn in the province of Quebec for neonatal hypothyroidism. To date, from 47,000 measurements, three newborn infants with abnormally low TBG and seven hypothyroid infants have been detected. From these data we conclude that the frequency of congenital hypothyroidism is about one in 7,000 births and that our method is effective in detecting thyroid hormone abnormalities with an acceptable percentage of false positive measurements; no false negative results have occurred to our knowledge.

Blood Specimen Collection↗