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BackgroundThis study was designed to establish a reference interval for sweat chloride for infants without evidence of cystic fibrosis (CF), aged between 5 wk and 6 wk, a time when sweat testing is an integral part of newborn screening for CF. In addition, we compared the gold standard method of sweat testing (quantitative pilocarpine iontophoresis [QPIT, coulometry]) with an emerging methodology (Macroduct™ [ISE]).MethodsThis was a prospective study on healthy infants at 5–6 wk of age. Sweat collection was undertaken at home on both outer thigh areas using two methods (QPIT and Macroduct™). The order of testing was randomly assigned. Filter paper samples (QPIT) were analysed using flame photometry and coulometry. Macroduct™ samples were analysed using ion-selective electrodes (ISE, Abbott Architect c8000, UK).ResultsInsufficient sweat was collected on 28 occasions with the QPIT (coulometry) method and on 31 with the Macroduct™ (ISE) capillary system. We achieved a 92% success rate in undertaking two sweat collections consecutively (n = 177). Sweat chloride concentrations were normally distributed with excellent limits of agreement between the two methods of sweat collection and analysis (n = 150). Median (IQR) sweat chloride was 11.2 mmol/L (8–13) with QPIT (coulometry) method with a 99.5th centile (n = 165) of 24 mmol/L.ConclusionThe Macroduct™ (ISE) capillary sweat collection system is valid in this age group. Sweat chloride concentrations above 30 mmol/L should prompt assessment in a specialist CF centre.

Aims: To determine the factors which influence the suppression of thyroid-stimulating hormone (TSH) in infants with congenital hypothyroidism (CH) following treatment. Methods: We examined retrospectively the patterns of thyroid function tests from diagnosis to 3 years of age in 140 infants diagnosed with CH from screening. Patients were classified into 3 groups: athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. Adequate TSH suppression was defined as plasma TSH concentration Results: All infants had radionuclide scans prior to treatment: athyreosis (n = 39), ectopia (n = 78) and dyshormonogenesis (n = 23). 58% of patients had persistently raised TSH at 6 months of age while 31% of patients had a persistently raised TSH at 1 year of age. There was a significant delay in the normalisation of plasma TSH in athyreosis and ectopia groups compared with dyshormonogenesis. Multiple regression analysis for TSH suppression at 6 months of age found plasma T4 levels and aetiology of CH as independent factors affecting the timing of TSH suppression. Aetiology of CH was the only independent factor affecting TSH suppression at 1 year of age. Conclusion: At 6 months of age, plasma T4 levels at 6 weeks and 3 months, and aetiology of CH were independent factors affecting timing of TSH suppression. However, by 1 year of age, the aetiology of CH was the only independent factor affecting suppression of TSH.

Background: There is a poorly understood association between obesity and hypertension. We demonstrated abnormalities of adrenal androgen and cortisol metabolites in four hypertensive obese children. Patients: Four males (aged 10 to 15 years) were evaluated for systolic blood pressures consistently above the 99.6 th percentile. All were overweight with BMI ranging from 27-35. Clinical examinations, renal ultrasound and DMSA scans were normal. Plasma electrolytes, renin, aldosterone, cortisol, testosterone, ACTH and TSH were normal. 24-Hour urinary steroid profiles showed a generalised excess of adrenal androgen and cortisol metabolites in all cases. Relevant recognised disorders of adrenal androgen and cortisol metabolism were excluded. Conclusion: There is no clinical condition explaining these abnormal urinary steroid profiles. These results support previous findings and provide new data on abnormal urinary adrenal androgen excretion in obese hypertensive patients. Further studies may determine the relationship between obesity, hypertension and the observed abnormalities of urinary steroid excretion.

Background: A recent study suggested that sexual dimorphism affects initial thyroid function in congenital hypothyroidism (CH) but differs according to aetiology of CH. Aims: To determine if sexual dimorphism was associated with biochemical severity of CH and its aetiology in our large British population. Methods: We examined retrospectively the initial thyroid function tests of 140 infants diagnosed with CH from screening. All infants underwent Tc-pertechnetate radionuclide scans at diagnosis to establish the aetiology of CH prior to commencement of treatment. Patients were classified into athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. A comparison of males and females were made within the three aetiological groups for gestational age, birth weight, initial dose of levothyroxine (LT4), screening TSH, confirmatory plasma thyroxine (T4), confirmatory plasma TSH and age of TSH suppression. Results: There was no significant difference between sexes for gestation, birth weight and initial treatment dose in all aetiological subgroups. In thyroid ectopia, screening TSH and confirmatory plasma TSH were significantly higher in females compared with males (P < 0.01), while confirmatory plasma T4 were significantly lower in females (P < 0.05). No difference was detected between males and females in athyreosis and dyshormonogenesis subgroups for screening TSH, confirmatory plasma TSH and total T4. Conclusion: Sexual dimorphism influenced the biochemical severity of thyroid ectopia in congenital hypothyroidism in our British population. However, this effect was not apparent in patients with athyreosis or dyshormonogenesis. Further advances in the molecular genetics of CH are essential to evaluate this phenomenon further.

Carotenemia in infancy is a relatively rare but benign condition, invariably of dietary origin, that can be confused with jaundice. It is characterized by an abnormal yellowish orange pigmentation of the skin, most prominently seen in the palms, soles, and naso-labial folds. Infant feeding patterns have shown an increasing trend toward the usage of homogenized and pureed vegetables as well as meat-based commercial preparations. Whether this is reflected in an increased incidence of carotenemia in this age group still remains unclear. We report a series of infants identified by a retrospective review of records, observed over a 3-year period (1999-2002) in a tertiary children's hospital, who developed the condition that resolved spontaneously without intervention, as they grew older, on a changing diet.

Optimal management of congenital hypothyroidism (CHT) includes early diagnosis and prompt treatment.1–3 We conducted an audit over a 12-week period in 2002 to determine whether time of screening for CHT was in adherence to standards published by the UK Newborn Screening Programme. The minimum standards recommended for time of screening for …

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis. We report a patient who presented at 10 months of age with hypotonia and global developmental delay. Subsequently, she developed seizures and choreoathetosis. Magnetic resonance imaging showed high signal bilaterally in the globus pallidus on T2-weighted images. Mitochondrial respiratory chain studies revealed low complex I activity (in muscle 0.052 nmol NADH oxidized per min per unit citrate synthase, controls 0.166 +/- 0.047; in fibroblasts 0.080 nmol NADH oxidized per min per unit citrate synthase, controls 0.197 +/- 0.034). The true diagnosis was suspected at 21 months of age because of persistent low plasma and urine creatinine concentrations. GAMT activity was undetectable in fibroblasts and compound heterozygous mutations were found in the GAMT gene (c.327GA and c.522GA). The patient was treated with creatine, dietary arginine restriction and ornithine supplements. Her movement disorder and seizures resolved but she still has severe cognitive impairment and no expressive language. The occurrence of secondary respiratory chain abnormalities in GAMT deficiency may lead to misdiagnosis, particularly as the clinical and radiological features resemble those seen in mitochondrial encephalopathies. It is important to establish the correct diagnosis because specific treatment is available.

A mother with classical phenylketonuria was treated from the ninth week of pregnancy with a tyrosine augmented, low phenylalanine diet. Assessment of the infant up to the age of twelve months suggests normal development, although further follow up is planned.

SUMMARY [14C]Acetate was incorporated into dehydroepiandrosterone, pregnenolone and their sulphates and into cholesterol during incubations of adrenal tissue from three human foetuses of 10–18 weeks of gestation. No incorporation of [14C]acetate into cortisol or other 4-en-3-oxo steroids could be demonstrated. Porcine ACTH stimulated the incorporation of [14C]acetate into both dehydroepiandrosterone sulphate and cholesterol when added to incubations of adrenal tissue from foetuses of 18 weeks gestation. Such an effect was not observed with tissue from a 10-week-old foetus. Stimulation of steroid biosynthesis from [14C]acetate was also achieved by addition of human growth hormone or human chorionic somato-mammotrophin. These trophic hormones may therefore play some part in regulating the provision of precursors for oestrogen biosynthesis in pregnancy.

The viscosity at low shear rate of whole blood, plasma and serum, the haematocrit, plasma fibrinogen, plasma proteins, and IgM were measured in maternal and cord blood immediately following delivery. The whole blood viscosity in maternal blood (mean 19.96 +/- 3.74 centipoise or c/p) was similar to cord blood viscosity (mean 19.44 +/- 4.28 c/p). The mean haematocrit in maternal blood (0.385 +/- 0.026) was significantly lower than the cord haematocrit (0.488 +/- 0.39). Mean plasma viscosity (1.86 +/- 0.47 c/p) and plasma fibrinogen (4.25 +/- 0.75 g/litre) in maternal blood were significantly higher than cord plasma viscosity (1.12 +/- 0.19 c/p) and cord plasma fibrinogen (1.81 +/- 0.61 g/l). Mean serum viscosity (1.22 +/- 0.28 c/p) and mean IgM levels (2.38 +/- 0.36 g/l) in maternal blood were significantly higher than cord serum viscosity (0.90 +/- 0.15 c/p) and cord IgM (0.48 +/- 0.06 g/l). The low low levels of IgM and fibrinogen may protect the fetus from the increased viscosity that could be expected in association with a high haematocrit.

Creatine phosphokinase (CPK) levels during two consecutive pregnacies of a patient whose sister had died of malignant hyperpyrexia have been investigated. The results are compared with CPK levels of serum obtained from apparently normal people at similar stages of pregnancy. The rise of serum CPK occurring as a result of labour was much more pronounced in the malignant hyperpyrexia suspect.

The neurological sequelae of vitamin E deficiency occurring as a result of steatorrhoea, specific defects in fat absorption (abetalipoproteinaemia), and in a selective defect of vitamin E absorption (Harding et al., 1985) are now well described (Muller et al., 1983). The importance of assessing vitamin E status is illustrated in this report on the presentation, treatment and progress of an atypical case of hypolipoproteinaemia associated with cataracts and scoliosis.

The case presented illustrates the potential of assessing fetal pulmonary maturity by analysing liquor draining vaginally after premature rupture of the membranes. The necessity of carrying out appropriate biochemical tests to detect contamination with maternal urine is emphasized.

The concentration of corticosteroids in the umbilical vein plasma of babies delivered after a spontaneous onset of labour showed a significant positive correlation with the duration of labour (r=0-593; P less than 0-001) and the length of the second stage (r=0-48; P less than 0-02). Similar results were also obtained for induced labours. For labours of both induced and spontaneous onset, the albumin concentration in cord plasma also correlated significantly (r=0-46; P less than 0-01) with the corticosteroid concentration. It is concluded that the stress of labour and vaginal delivery, and possibly changes in the concentration of proteins which bind corticosteroids, are impoertant in determining the corticosteroid concentration in cord plasma obtained after delivery of the baby. The significance of these findings in relation to mechanisms responsible for the onset of human labour is discussed.

Though the clinical and biochemical features of medium chain acyl-CoA dehydrogenase deficiency are now becoming well established we have much less experience of defects in short chain acyl-CoA dehydrogenation. The patient described here demonstrated defective oxidation of butyrate and hexanoate by cultured fibroblasts but normal oxidation of both medium and long chain fatty acid substrates, indicating a specific short chain abnormality. In keeping with this the urine contained excessive ethylmalonic acid.