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L T Kirby

Publications and source records attributed to L T Kirby.

18 recordsLinked to original sources
PubMed1994

On the molecular nature of the Duarte variant of galactose-1-phosphate uridyl transferase (GALT).

Galactosemia is an inborn error of galactose metabolism secondary to deficiency of galactose-1-phosphate uridyl transferase (GALT). GALT is a polymorphic enzyme and Duarte (D) is the most common enzyme variant. This variant is characterized by faster electrophoretic mobility and reduced activity. Duarte/galactosemia compound heterozygotes (D/G) are commonly identified in galactosemia newborn screening programs. However, these patients do not generally require treatment. By using a "candidate mutation" approach to define the molecular basis of the Duarte variant of GALT, a close association between the previously reported N314D polymorphism and the Duarte variant of GALT was found. We suggest that N314D encodes the D variant of GALT and that molecular testing for N314D might be useful to confirm a biochemical diagnosis of Duarte variant of GALT.

Alleles↗
PubMed1990

Molecular analysis of autosomal dominant neurohypophyseal diabetes insipidus.

The status of the arginine vasopressin-neurophysin-II (AVP-NPII) gene was studied in three families with autosomal dominant neurohypophyseal diabetes insipidus (AD-NDI). Restriction fragments of genomic DNA containing AVP-NPII sequences from affected individuals were not detectably different in size from those of normal controls. Thus, these individuals with ADNDI do not have apparent large deletions, insertions, or rearrangements of an AVP-NPII allele. Four restriction fragment length polymorphisms were detected with a probe for the adjacent gene on chromosome 20, oxytocin-neurophysin-I (OT-NPI). Linkage studies in these three families between the restriction fragment length polymorphism haplotypes and ADNDI phenotype strongly suggest cosegregation. This indicates that the genetic locus for ADNDI maps within or near the AVP-NPII locus and suggests that a defective AVP-NPII allele may be the basis of ADNDI.

Arginine Vasopressin↗
PubMed1985

Screening of newborn infants for galactosemia in British Columbia.

With simple microbiologic and fluorescent tests, we detected two cases of classic galactosemia, confirmed by specific enzyme assays, in the first 25 000 newborn infants in British Columbia screened for this disorder. The results were equivocally abnormal for another 31 infants, and a second blood sample was requested from each, either for repeat screening or for enzyme assays. The two infants with galactosemia were in hospital with an undiagnosed acute illness and had only a trace of non-glucose reducing substances in the urine when the screening tests were done. Screening for galactosemia fits well with our established programs of screening for phenylketonuria and hypothyroidism and costs less than $1 per infant tested.

British Columbia↗
PubMed1985

Genetic analysis of carbamyl phosphate synthetase I deficiency.

Carbamyl phosphate synthetase I deficiency (CPSD) is an autosomal recessive disorder of ureagenesis characterized by hyperammonemic coma in the neonatal period. To study the genetic basis of CPSD we have performed a molecular analysis of the CPS I genes in CPSD patients from six unrelated families. Using a cDNA probe for the human CPS I gene and restriction endonuclease mapping techniques, we observed no abnormality in the number of size of the hybridizing DNA fragments from the seven affected individuals examined. These findings suggest that no gross alteration affected the CPS I genes. We did detect a frequent restriction fragment length polymorphism (RFLP) at the CPS I locus which we employed as a linkage marker. Our results suggest the polymorphic CPS I restriction fragments cosegregate with the CPSD phenotype, and that linkage disequilibrium exists between the CPSI RFLPs studied and the affected alleles. The RFLPs described may enable prenatal detection of CPSD in families where the coupling phases between CPSD alleles and RFLPs can be determined.

Alleles↗
PubMed1984

Immunoreactive trypsin in cystic fibrosis.

Since the first observation in 1979 that CF infants have elevated blood IRT, studies in various centres have enabled us to more fully understand the importance of this phenomenon. There is increasing evidence to show that mass newborn screening for CF using the IRT assay is practical and is capable of detecting essentially all CF newborns at a cost comparable to existing screening programs for other disorders such as Hypothyroidism. Although the elevated IRT levels seen in infancy in CF soon decrease, IRT levels in older CF patients appear to quite closely reflect the capability of that patient to secrete pancreatic enzymes and can be helpful in separating CF patients whose ability to secrete enzymes is preserved, from those with diminished exocrine pancreatic function. In all CF patients there appears to be an altered relationship between pancreatic exocrine secretion and circulating IRT levels as compared to control patients. This is probably one further manifestation of a secretory obstructive defect which although not uniformly severe, is common to all CF patients.

Adolescent↗
PubMed1983

The prognosis of hyperlysinemia: an interim report.

Ten patients with familial hyperlysinemia with lysine-ketoglutarate reductase deficiency, identified through newborn screening programs or family surveys, were selected for review. Ages ranged from 2 to 24 years when last examined. A low-protein diet had been administered to two patients, which reduced the plasma lysine levels from 20 mg per dl or more to about 12 mg per dl. The rest were untreated. Mental development was judged normal or above average in nine. Mildly subnormal performance in three was considered appropriate to family and social background. No adverse mental or physical effects could be attributed to the hyperlysinemia. A normal child has been born to a mother with hyperlysinemia, indicating that the fetus may develop normally despite exposure to high lysine levels.

Adolescent↗
PubMed1981

Use of a dried blood spot in immunoreactive-trypsin assay for detection of cystic fibrosis in infants.

We assayed more than 5000 blood spots dried on filter paper and approximately 1000 serum samples for immunoreactive trypsin, with commercial reagents (Behring and Sorin). The assay procedures were modified so that newborn screening is technically feasible. Both kits are satisfactory for serum assay, but the Sorin materials are better adapted for blood spot analysis. Immunoreactive trypsin in blood spots rapidly decreases with specimen age, but is stable in frozen serum. Values for premature infants do not differ significantly from those for full-term babies. Children with cystic fibrosis were readily distinguished from those without, up to at least one year of age.

Blood Specimen Collection↗
PubMedDate not supplied

Prenatal diagnosis of non-ketotic hyperglycinemia.

We describe successful prenatal diagnosis in four pregnancies at risk for non-ketotic hyperglycinemia, two affected and two unaffected, using the glycine level and the glycine/serine ratio in amniotic fluid obtained at 16 weeks gestational age. Although this method of prenatal diagnosis for non-ketotic hyperglycinemia has been effective in our hands the narrow differences between affected and unaffected pregnancies indicate the need for caution concerning its reliability.

Amino Acid Metabolism, Inborn Errors↗