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Biomedical subjects

S Worthington

Publications and source records attributed to S Worthington.

14 recordsLinked to original sources
PubMed2001

Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses.

Inherited succinic semialdehyde dehydrogenase (SSADH; EC1.2.1.24; McKusick 271980) deficiency is a defect of GABA degradation which leads to accumulation of 4-hydroxybutyric acid (gamma-hydroxybutyric acid; GHB) in physiologic fluids of patients. Prenatal diagnosis (PND) was performed in three at-risk pregnancies employing combinations of: (1) reverse-transcription-polymerase chain reaction (RT-PCR) and genomic DNA amplification followed by sequencing using isolated leukocytes or cultured human lymphoblasts; (2) GHB quantitation in amniotic fluid; or (3) SSADH enzyme assay in chorionic villus (CV) and/or amniocytes. In two pregnancies, all analyses were concordant for prediction of disease status in the fetus. In the third case, enzyme activity in CV (deficient) and metabolite analysis in amniotic fluid (normal) were discordant. For clarification, mutation analysis was undertaken in CV, confirming heterozygosity for the mutation previously identified in the proband. We hypothesize that delayed transit time for shipment of CV between Greece and the United States (8 days) led to enhanced degradation of heterozygous SSADH enzyme activity. Our data demonstrate the importance of combined metabolite, enzyme, and DNA analysis for increased accuracy in the PND of SSADH deficiency.

Aldehyde Oxidoreductases↗
PubMed2000

A case of maternal uniparental disomy of chromosome 9 diagnosed prenatally and the related problem of residual trisomy.

Non-mosaic trisomy 9 was found in a chorionic villus (CV) sample taken from a 43-year-old woman referred for prenatal chromosome analysis due to advanced maternal age. Follow-up amniocentesis revealed level 2 mosaicism for trisomy 9. Trisomy 9 was not detected at fetal blood sampling. Molecular analysis of fetal (amniocyte) DNA showed maternal uniparental heterodisomy (UPD) for chromosome 9. Two crossovers resulted in a region of isodisomy in the distal long arm. Trisomy rescue of a meiosis 1 segregation error seems to have been responsible for the uniparental disomy of chromosome 9. The pregnancy continued and neonatal blood testing showed a mosaic trisomy 9 karyotype, i.e. 4/50 cells analysed. Clinical postnatal follow-up for a period of 1 year has documented only minor facial dysmorphism and skeletal abnormalities. Development appears unremarkable. This case is the second report of maternal uniparental disomy for chromosome 9 detected prenatally and is the first case followed up post-term. This report highlights the difficulty of making informed prognostic assessments in such cases despite extensive laboratory investigation.

Adult↗
PubMed1998

22q11 deletions in patients with conotruncal heart defects.

OBJECTIVE: To ascertain the frequency of 22q11 deletions in a representative population of conotruncal heart defects (CTD) and determine which children are at risk of having a deletion. METHODOLOGY: A clinical and laboratory evaluation of 90 children with CTD, including isolated and syndromic cases. RESULTS: Fifteen children (17%) were shown to have 22q11 deletions by fluorescence in situ hybridization (FISH) studies with the Oncor probe N25. Varying degrees of developmental delay/learning disabilities and facial dysmorphism were common in these children. None of the isolated cases without dysmorphism had a deletion. CONCLUSION: 22q11 deletions are a significant cause of a specific form of congenital heart disease, CTD. It is important to have a high index of suspicion of the 22q11 deletion disorders in children with CTD and other extracardiac manifestations so that the diagnosis can be made early and appropriate interventions implemented.

Abnormalities, Multiple↗
PubMed1997

Atelosteogenesis syndromes: a review, with comments on their pathogenesis.

The clinical, radiographic, and morphological findings in 25 cases of atelosteogenesis and boomerang dysplasia have been reviewed. The review confirms the nosologic grouping of atelosteogenesis type I with boomerang dysplasia and the clinical and radiographic overlap of features between atel- osteogenesis I and atelosteogene- sis II (synonymous with De la Chapelle dysplasia) and a group of patients with atelosteogenesis type III. A common pathogenesis is suggested for atelosteogenesis type I and boomerang dysplasia. A marked excess of male fetuses with boomerang dysplasia was observed. Atelosteogenesis type II shows distinctive chondro-osseous histopathology with a major disturbance in cartilage matrix macromolecules. An overlap of phenotypic, radiographic, morphological, and cartilage histochemical features with those observed in diastrophic dysplasia and achondrogenesis type IB suggests that atelosteogenesis type II has common pathogenetic features with disorders of sulfation of connective tissue matrix macro- molecules.

Bone Diseases, Developmental↗
PubMed1997

Carbohydrate deficient glycoprotein syndrome type I: a cause of cerebellar vermis hypoplasia.

To report the first case of carbohydrate deficient glycoprotein syndrome Type I (CDG I) that has been identified in Australia and confirmed enzymatically to raise the awareness of paediatricians with regard to CDG I and its manifestations, implications and diagnostic investigations. Clinical and autopsy findings of an infant with CDG I are presented. The diagnosis of CDG I was suggested by the clinical findings and biochemical abnormalities and was confirmed by showing an abnormal transferrin isoform pattern. Subsequent studies showed a reduced level of phosphomannomutase in skin fibroblasts. Carbohydrate-deficient glycoprotein syndrome I is one of the many causes of cerebellar hypoplasia. It is an important disorder to identify because of the prognostic and genetic implications and may be underdiagnosed in Australia.

Cerebellum↗
PubMed1997

Anal anomalies: an uncommon feature of velocardiofacial (Shprintzen) syndrome?

We report three cases of velocardiofacial syndrome (VCFS) with anal anomalies who have deletions of the 22q11 region and a further case where the proband has VCFS clinically and her father has an anal anomaly. It is important to consider VCFS in the differential diagnosis of children with anal anomalies and to look for other features of the syndrome, such as asymmetrical crying facies, submucous cleft of the palate, developmental delay, cardiac anomalies, and hypoparathyroidism.

Abnormalities, Multiple↗
PubMed1996

Pregnancy and argininosuccinic aciduria.

We present the outcome of a pregnancy in a woman with mild argininosuccinic lyase deficiency to add to the collective experience of the maternal and fetal effects of urea cycle defects. In females affected with argininosuccinic lyase deficiency, careful clinical and biochemical monitoring of pregnancy will minimize the risk of metabolic decompensation in the perinatal period. Furthermore, it would appear that argininosuccinate is not teratogenic to the development of the human fetus.

Adult↗
PubMed1986

The decline in congenital rubella syndrome in Western Australia: an impact of the school girl vaccination program?

Rubella vaccination became available in 1970 in Australia. In Western Australia (WA), a school girl vaccination program was well established by 1971. Mothers under 26 years of age in 1983 would have been eligible for this program and they constitute 40 per cent of WA births. Data on Congenital Rubella Syndrome (CRS) cases were obtained for years of birth 1968-83 inclusive to ascertain if there had been an impact of the program on the CRS rate. Epidemics of rubella occurred in 1970-71, 1974, and 1979-80. The CRS rate has fallen steadily; it did not rise during the 1979-80 epidemic and was less than one in each year after 1977. All CRS cases born since 1974 were to mothers too old to have been eligible for the program. The data suggest that the vaccination program is effective, but this cannot be proven until data become available on pregnancy terminations.

Adolescent↗
PubMed1985

The first observation of Hb D Punjab beta zero thalassaemia in an English family with 22 cases of unsuspected beta zero thalassaemia minor among its members.

A 36 year old local Englishman from Nuneaton was referred to hospital with suspected glandular fever. Relevant tests were negative and the symptoms subsided in due course. The finding of a hypochromic microcytic blood picture without iron deficiency led to the discovery that he was heterozygous for Hb D and beta thalassaemia. Hb D trait was established in the father of the proband and beta thalassaemia in his mother and a brother. The father's ancestors were miners who came to Nuneaton from Monmouthshire in the 19th century. The mother's ancestors have belonged to the indigenous population of Nuneaton and neighbouring Leicestershire since the 18th century. Twenty local members of her wider family also had thalassaemia. All thalassaemias had a low MCH and raised level of Hb A2. The Hb F level, however, was normal in five, demonstrating the independent segregation of genetic factors influencing the Hb F level in beta thalassaemia trait.

Adolescent↗
PubMedDate not supplied

Nurse-midwifery evaluation and management of cervical pathology and the colposcopic examination.

Over the last several years, there has been a steady increase in the number of women experiencing abnormal Papanicolaou test results. Whether the nurse-midwife is performing a colposcopic examination or making a referral, she or he needs to have a clear understanding of cervical pathophysiology, diagnostic modalities, and therapeutic management. This article provides the nurse-midwife with a basic review of the cytologic and histologic findings of the cervix, a description of the colposcopy procedure, observations, terminology, and follow-up treatment, and considerations for adding colposcopy to a nurse-midwifery practice.

Aftercare↗
PubMedDate not supplied

Genetic screening.

The family planning nurse practitioner may be the client's only link to genetic screening, education, and counseling. The principles of genetics, the types of genetic defects and their causes are presented. Clients at risk and the nurse practitioner's role in providing education, support, counseling, and referrals are discussed.

Chromosome Aberrations↗