Neonatal presentation of medium-chain acyl-CoA dehydrogenase deficiency in two families.
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Acyl-CoA Dehydrogenase↗
Biomedical subjects
J M Kirk
Publications and source records attributed to J M Kirk.
The neuroradiology of Kallmann's syndrome: a genotypic and phenotypic analysis.
A detailed neurological investigation of patients with Kallmann's syndrome (KS) has been performed in an attempt to relate phenotypic characterization with genotype. Twenty-seven subjects with KS were studied (including 12 males with X-linked disease and 3 females). Six male and 2 female normosmics with isolated GnRH deficiency, 1 male with KS variant, and 1 obligate female carrier were also imaged. Evidence for X-linked disease was derived both from analysis of pedigree and by mutation analysis at the KAL locus. The female carrier and all 8 normosmics had normal olfactory bulbs and sulci, as did 3 male KS. The study, therefore, confirms the value of magnetic resonance imaging in the diagnosis of KS, but suggests that the technique is not sufficiently sensitive to differentiate KS from the normosmic form of GnRH deficiency in all cases. Phenotypic characterization of KS was more effectively achieved by accurate estimation of olfactory status. Three new mutations at the KAL locus were identified, 2 single exon deletions and 1 point mutation. In 2 pedigrees with clear X-linked inheritance, no coding sequence mutations were detected; it may be that these harbor mutations of pKAL, the recently characterized 5'-promoter region. No clear relationship could be established between specific phenotypic anomalies and particular KAL mutations. Involuntary, mirror movements of the upper limbs were present in 10 of 12 cases of X-linked KS, but in none of the other subjects. Although this phenomenon has been ascribed to an abnormality of the corpus callosum, in the present study magnetic resonance imaging demonstrated no quantitative or qualitative morphological anomalies of this structure.
Base Sequence↗
Transcutaneous bilirubinometry as a screening tool for neonatal jaundice.
Between 25 and 50% of all term newborns develop clinical jaundice, and a serum bilirubin level above 260 microml/l (15 mg/dl) is found in 3% of normal term infants. In the United Kingdom many newborn infants with clinical jaundice have blood samples sent to biochemistry laboratories for assessment of the plasma bilirubin concentration. We planned to assess the cost in terms of finance, medical staff time, numbers of blood samples, and family delay in leaving hospital. We demonstrated that reflectance bilirubinometry is a reliable screening method for identifying which caucasian infants require to have plasma bilirubin concentrations measured in the laboratory. The Minolta Airshields transcutaneous bilirubinometer provided reproducible data, saved time and costs, and often spared infants a capillary or venous blood sample. The transcutaneous bilirubinometer provides a digital assessment of skin pigmentation by xenon reflectance. It has previously been shown to be possible to derive an estimate of plasma bilirubin from the number displayed by the meter and it is suggested as a method for identifying which infants need plasma bilirubin estimations.
Bilirubin↗
First trimester diagnosis of primary hyperoxaluria type I.
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Blotting, Southern↗
Antibiotic interference in urinary thiosulphate measurements.
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Anti-Bacterial Agents↗
The implementation of a quality management system in a department of diagnostic radiology.
The quality management systems of the Departments of Diagnostic Radiology of St George's Hospital, London, and Bristol Royal Infirmary (BRI) have been certified with the British Standard 5750. These were the first clinical departments in the UK to be certified to this internationally recognized quality assurance (QA) standard. Quality is a much used term; in this context it is defined as 'fitness for purpose', and quality assurance is the mechanism by which quality is achieved. The paper describes the features of the quality system which have been implemented at St George's Hospital, and how a management concept for manufacturing industries has been adapted successfully to a National Health Service Department. The paper also demonstrates how the quality system has led to the setting and achieving of departmental objectives.
England↗
Intraluminal bile duct hepatocellular carcinoma.
Jaundice is usually a late feature in the course of hepatocellular carcinoma and is only rarely due to obstruction. We present two cases of obstructive jaundice, in which the cause of obstruction in both patients was a massive intraluminal filling defect within the common bile duct which proved to be hepatocellular carcinoma. The radiological features are described.
Aged↗
Identification of olfactory dysfunction in carriers of X-linked Kallmann's syndrome.
OBJECTIVE: The aim of the study was to test the hypothesis that clinically unaffected female carriers of X-linked Kallmann's syndrome have an olfactory defect. DESIGN: Assessment of the olfactory threshold to seven standard odorants, each at a concentration of 1-10(-8) mol/l. PATIENTS: Five families with X-linked Kallmann's syndrome (KS) were tested, containing 19 males with KS, and 9 female carriers. Related but unaffected males (n = 8) were used as a control group, and in addition seven patients with Turner's syndrome (XO) were assessed. MEASUREMENTS: The olfactory threshold was taken as the lowest concentration at which each odorant was clearly distinguished from control (liquid paraffin). The threshold for each odorant was compared between the subject groups using the non-parametric Mann-Whitney test. RESULTS: All patients with KS were anosmic to all odorants. The female carriers had hyposmia, with a significant reduction in the olfactory threshold to putrid, peppermint, floral and pungent odorants compared to control subjects, and to peppermint, floral and pungent odorants compared to subjects with Turner's syndrome. The latter had olfactory thresholds which were statistically identical with the control group. CONCLUSIONS: Obligate female carriers of X-linked Kallmann's syndrome are hyposmic compared to control subjects. The overlap between the two groups, however, makes olfactory testing unreliable as a diagnostic test.
Female↗
Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity.
OBJECTIVE: Therapy with GHRH in patients with mild GH insufficiency appears to be more effective than in those with severe insufficiency. We, therefore, studied the clinical response of children with idiopathic short stature to treatment with GHRH(1-29)NH2 (GHRHa) for a period of 12 months. DESIGN: Eighteen short pre-pubertal children (aged 4.3-11.0 years, 17 male) with idiopathic short stature (height < 3rd centile, peak GH to provocative testing > 20 mU/l) were recruited to receive GHRHa 20 micrograms/kg by twice daily s.c. injection for one year. One patient was non-compliant and was withdrawn prior to 3 months of therapy. Pretreatment height velocity was calculated for 12 months and subjects were measured 3-monthly during therapy. Overnight GH profiles and s.c. GHRH tests (20 micrograms/kg) were performed at 0, 3, 6 and 12 months of therapy. In addition, an i.v. GHRH test (1 microgram/kg) was performed at the start and after 1 month of therapy. MEASUREMENTS: Overnight GH profiles were analysed using the Pulsar program. RESULTS: Mean (SD) height velocity (HV) increased from 4.8(0.9)cm/year pre-treatment to 7.2(1.6)cm/year after 12 months of therapy (P = 0.001). The children growing slowly (HV < 25th centile) before treatment had a greater growth response than those growing normally (HV > or = 25th centile) before treatment. Final height prediction increased by a mean (SD) of 3.4(2.6)cm. Overnight GH levels and GH responses to GHRH testing fell during the 12 months of therapy. Fasting blood glucose and insulin levels increased during therapy, as did IGF-I. Cessation of GHRHa was followed by catch-down growth during the first 3 months off therapy: mean (SD) HV 3.89(1.82)cm/year (P < 0.04), although the HV after 6 months (4.9(1.0))cm/year) and 12 months (4.4(1.0)cm/year) was not different from pretreatment values. CONCLUSIONS: Short-term therapy with twice-daily s.c. injection of GHRHa (20 micrograms/kg) promoted linear growth in short children who were not GH-insufficient. The improved height velocity was sustained throughout the 12 months of treatment, followed by catch-down growth, and returned to pretreatment velocity after cessation of therapy.
Blood Glucose↗
Gonadal function and response to human chorionic and menopausal gonadotrophin therapy in male patients with idiopathic hypogonadotrophic hypogonadism.
OBJECTIVE: This study was designed to determine the response to therapy using human chorionic gonadotrophin (hCG) and human menopausal gonadotrophin (hMG) in males with idiopathic isolated hypogonadotrophic hypogonadism (IHH), and to compare the responses in patients presenting with and without cryptorchidism. DESIGN: Analysis of male patients with IHH treated with hCG or combined hCG/hMG for a minimum of 6 months at St Bartholomew's Hospital. Clinical and endocrine assessment was performed in all patients prior to commencing therapy. PATIENTS: A total of 26 males with IHH have been treated with exogenous gonadotrophins. Thirteen patients (Group 1) had cryptorchidism (unilateral in 7, bilateral in 6) at presentation, and 13 (Group 2) did not. MEASUREMENTS: All patients had basal serum testosterone, LH and FSH determinations. An i.v. GnRH test was performed in 25 patients and an i.m. hCG stimulation test in 19. Testicular volume and serum testosterone were measured during both hCG and combined hCG/hMG therapy. Seminal analysis was performed at the start and monthly during hCG/hMG therapy. RESULTS: Eighty-five per cent of the 13 patients in Group 1 had an olfactory defect (Kallmann's syndrome), compared with 23% of Group 2. Both groups of patients showed a subnormal response to initial i.v. GnRH and i.m. hCG testing. During hCG therapy only three patients in Group 1 and six in Group 2 achieved normal adult testosterone levels. The non-cryptorchid group achieved a higher mean testicular volume on hCG therapy than the cryptorchid group (mean (SD); 4.7 (1.8) ml vs 3.0 (1.6) ml (P < 0.02)), and for all patients there was a correlation between initial and maximal testicular volume (R = 0.69, P = 0.001). Four patients in Group 1 and five patients in Group 2 were treated with combined hCG/hMG for 6-15 months to induce fertility; only one patient in Group 1 achieved spermatogenesis, compared to all patients in Group 2 (leading to three pregnancies). CONCLUSIONS: These data indicate that patients with idiopathic hypogonadotrophic hypogonadism (IHH) have a poor response to hCG therapy in terms of testicular growth and normalization of serum testosterone. Final testicular volume is dependent on initial testicular size. In addition, patients with IHH associated with cryptorchidism have a poor fertility potential to combined hCG/hMG therapy.
Adolescent↗
Unilateral renal aplasia in X-linked Kallmann's syndrome.
Unilateral renal agenesis is an uncommon association with Kallmann's syndrome (KS) (hypogonadotrophic hypogonadism and olfactory defect). We have investigated affected individuals from six pedigrees: five with X-linked KS, and one with X-linked KS and X-linked ichthyosis (XLI). Seventeen affected individuals have had renal imaging performed, and six scans demonstrated only one kidney. In addition, two pedigrees had males who died in the neonatal period with bilateral renal agenesis. Only two of the four affected individuals in the family with X-linked KS and X-linked ichthyosis (Pedigree 6) showed unilateral renal agenesis, despite all four patients demonstrating an interstitial deletion within the short arm of the X-chromosome. These data indicate that unilateral renal agenesis is much commoner than previously suspected in patients with X-linked Kallmann's syndrome, but that it may have incomplete penetrance within a family.
Genetic Linkage↗
Intrathoracic extra-mediastinal cystic hygroma in infancy.
An infant with intrathoracic extra-mediastinal cystic hygroma is described. Fluid collection within the fetal chest was noted on routine antenatal ultrasound scan and this was subsequently drained. Postnatally, echocardiogram and thoracic CT scan demonstrated a cystic space between the pericardium and right mediastinal pleura. Thoracotomy performed at six weeks of age showed a multiloculated cystic mass adherent to the right pericardium and to the medial aspect of the diaphragm. Histology revealed the tumour to be a cystic hygroma (lymphangioma). Intrathoracic cystic hygroma occurring outside the mediastinum is extremely rare and has never been diagnosed previously in infancy.
Humans↗
Acceleration of pubertal development following pituitary radiotherapy for Cushing's disease.
A 7-year-old boy with pituitary dependent Cushing's disease was treated with pituitary irradiation following unsuccessful microadenomectomy. This led to normalization of the hypercortisolaemia, but was followed by GH deficiency. Two years after radiotherapy he had the onset of pubertal development with testicular enlargement to 8 ml bilaterally. Pubertal regression was induced using the long-acting GnRH analogue goserelin. Acceleration of skeletal maturation was also arrested, resulting in improvement of final height prediction. Irradiation directly to the hypothalamo-pituitary region, as well as whole brain irradiation, may thus be associated with accelerated pubertal development.
Child↗
Rhizomelic chondrodysplasia punctata with isolated DHAP-AT deficiency.
An infant with the characteristic phenotype of classical rhizomelic chondrodysplasia punctata was found to have an isolated deficiency of the peroxisomal enzyme acyl CoA dihydroxyacetone phosphate acyltransferase (DHAP-AT). All other peroxisomal functions measured were found to be normal. Previously described in one other case report, this confirms the existence of another distinct form of peroxisomal disorder characterised biochemically by a deficiency in de novo plasmalogen biosynthesis only.
Acyltransferases↗
Growth in CHARGE association.
Growth data is shown from 44 children (aged 0.5-18 years; 27 boys, 17 girls) with CHARGE association. Children had a normal birth weight and length, but in infancy there was a fall in centiles. Children remained small and there was pubertal delay in boys. Close monitoring of growth with early detection and intervention is recommended.
Abnormalities, Multiple↗
Accuracy of the typical computed tomographic appearances of fibrosing alveolitis.
BACKGROUND: Open lung biopsy is often performed to confirm the diagnosis in patients with suspected fibrosing alveolitis. The superior sensitivity and specificity of high resolution computed tomography (CT) over chest radiography in various diffuse lung diseases suggest that the characteristic appearance of fibrosing alveolitis on high resolution CT might render biopsy confirmation unnecessary. METHODS: The chest radiographs and high resolution CT scans of 86 patients (41 with fibrosing alveolitis and 45 with various other diffuse lung diseases) were examined individually and independently by two observers. No clinical information was given and the observers gave a level of confidence when the diagnosis was thought to be fibrosing alveolitis. RESULTS: The observers correctly and confidently discriminated between fibrosing alveolitis and other diffuse lung diseases on high resolution CT with an accuracy of 88% and on chest radiography with an accuracy of 76%. The false negative rate for fibrosing alveolitis diminished from 29% on chest radiography to 11% on high resolution CT. The false positive rate on chest radiography was 19% and on high resolution CT 13%; the false positive diagnoses on CT were the result of a few conditions (extrinsic allergic alveolitis, sarcoidosis, cryptogenic organising pneumonia, and pulmonary eosinophilia) which mimicked some of the CT features of fibrosing alveolitis. The superficial similarity of the CT patterns of these conditions are discussed. CONCLUSIONS: High resolution CT is superior to chest radiography in establishing the diagnosis of fibrosing alveolitis and the typical CT appearances are virtually pathognomonic. The diagnostic advantages of CT over chest radiography should further reduce the need for open lung biopsy in this condition.
Biopsy↗
The usefulness of serum thyroglobulin in the follow-up of differentiated thyroid carcinoma in children.
Serum thyroglobulin has been measured serially in ten children aged 5-17 years presenting with differentiated thyroid carcinoma. At presentation 4 had intra-thyroidal disease, 3 had lymph node metastases, and 3 had lung metastases. During follow-up for a median of 37.0 months (range 21-108) 3 patients have been disease-free, 4 have had a local relapse, and 3 have had persistent disease. Seventy-seven separate serum thyroglobulin measurements have been performed; 36 on and 41 off thyroid replacement therapy. A level of thyroglobulin of less than 5 ng/ml was taken as indicative of absence of disease, and compared against combined clinical examination and 131I scanning. Overall sensitivity of thyroglobulin measurement was 36/37 (97%), and although specificity was 30/40 (75%), this rose to 30/32 (94%) if raised thyroglobulin levels noted within 3 months of 131I therapy in otherwise asymptomatic patients (n = 4) or in subjects with intact thyroid tissue (n = 4) were excluded. Concordance with clinical status was 30/31 (97%) in measurements taken on, and 31/32 (94%) in those taken off, thyroid replacement. These data indicate that thyroglobulin measurement is a sensitive and specific means of detecting residual, recurrent, and metastatic thyroid carcinoma in children.
Adenocarcinoma↗
Surgical reinforcement of gender identity in adolescent intersex patients.
The presentation of phenotypic gender ambiguity at the time of adolescence is uncommon. Surgical reinforcement of gender, or reassignment is often complex and multistage. We present 2 cases of children who developed secondary sexual characteristics contrary to their chromosome status who, because of their late presentation, required significant surgical intervention to reinforce the gender assigned to them. We review some of the surgical techniques involved.
Adolescent↗