Anne Green

Pregnancy and inherited metabolic disorders: maternal and fetal complications.

Some inherited metabolic disorders (IMDs) can cause significant complications during pregnancy, affecting the mother and/or the fetus. Although it appears that only a minority of IMDs have these effects, experience is still being acquired. For some disorders, patients will not have reached child-bearing age. Pregnancies in this group of patients will increase as the management of IMDs in childhood and adolescence improves. Clinicians should be aware of potential complications and consider carefully how best to manage these conditions. Ideally, patients should be followed up in adult life by a specialized clinical team, which can implement a planned approach to conception and pregnancy, but often this is not possible. For disorders where the risk of complications is well established (e.g. phenyl-ketonuria), optimal treatment may lead to a good fetal and maternal outcome. It is important also to consider the possibility of an IMD being present in fetuses of pregnancies that are affected by non-immune hydrops, maternal HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) or acute fatty liver of pregnancy.

Plasma and Urine Amino Acid Concentrations in Children with Chronic Renal Insufficiency

Amino acids were determined in plasma and urine from controls and children with chronic renal insufficiency. Significant differences were found in the mean plasma concentration of serine, threonine, glutamic acid, tyrosine, arginine, cystine and glycine in children with severe renal failure. There was a marked increase in clearance of the majority of amino acids when glomerular filtration rate (GFR) fell below 30 ml/min/1.73 m2: the exceptions were the basic amino acids and cystine which did not change. As GFR decreased there was a significant reduction in the percentage tubular reabsorption of individual amino acids. Children with severe renal failure excreted up to 40% of the filtered load of amino acids in the urine. This significant increase in urinary amino acid loss may contribute to the derangement of plasma amino acid conentrations found in uraemia.

Untreated homocystinuria: a maternal death in a woman with four pregnancies. Case report

The patient, who was diagnosed to be homozygous for homocystinuria a t 11 years of age in 1967, had four pregnancies between 1975 and 1985. She had been lost to follow-up since 1974, and was never treated, the condition being unrecognized in her first two pregnancies. In 1961 surgical correction for dislocated lenses had been performed. Her first pregnancy in 1975 when she was 18 years of age ended in a premature stillbirth at 28 weeks gestation; the baby weighed 1180 g. An activated partial throniboplastin time performed at this time was within the normal range. The second pregnancy in 1983 ended in a spontaneous abortion at 10 weeks gestation. The patient was pregnant for the third time at 27 years of age in 1984. Caesarean section was performed at 31 weeks gestation for intrauterine growth retardation and fetal distress. The baby weighcd 930 g and survivcd. Postoperatively she was treated with anti-embolic stockings and a 7-day course of subcutaneous heparin. There were no problems in the puerperium. In 1985 at 28 years of age she booked at 17 weeks gestation in her fourth pregnancy and was seen regularly to 29 weeks gestation. At this visit intrauterine growth rctardation was suspected clinically and confirmed by ultrasound scan. Hypertension without proteinuria was also noted. Antenatal cardiotocography suggested fetal compromise, and therefore an emergency lower segment caesarean section was performed under general anaesthesia. The newborn infant

Neuroblastoma-When are urinary catecholamines and their metabolites 'Normal'?

The overproduction of catecholamines and their metabolites is a well recognised feature of neuroblastoma. Published data are scarce for their urinary excretion in children with neuroblastoma and in ill children in whom this diagnosis may be considered. We have determined a graphical upper reference limit for total catecholamines, total metadrenalines and HMMA in urine, expressed as a ratio to the creatinine concentration, for a group of 174 children with neuroblastoma and 704 hospitalised children with other disorders. This graph has been determined by examining the overlap region between the results for the two groups of children and avoids the irregularities caused by statistical outliers. The sensitivity and specificity of the individual tests indicate that total catecholamines is marginally the best single test to perform when trying to diagnose neuroblastoma, with the best clinical sensitivity being achieved by examining both total catecholamines and HMMA. Only two of the 174 children with neuroblastoma would not have been detected using these two tests. Total metadrenalines did not appear to add any further information and could be dropped from the repertoire in favour of the other two measurements.

Interference from heparin in commercial heparinised tubes in the measurement of plasma sodium by ion selective electrode: a note of caution

Sodium and potassium concentrations were measured in both whole blood and plasma from a series of 21 patient samples using a Corning 902 ISE. The difference between whole blood and plasma values for both analyses was not significant. The correlation coefficient and slope for sodium was 0·988 and 0·966 and for potassium was 0·998 and 1·04. A series of serum specimens (n=88), and a different series of plasma specimens, were each analysed by ISE and FE.

The Cryopreservation of Skin Biopsies—A Technique for Reducing Workload in a Cell Culture Laboratory

A method is described for the cryopreservation of skin biopsies at −70°C for subsequent possible reculture. Biopsies stored up to 1 year could be successfully recultured without affecting the time to achieve confluence or the culture failure rate. This technique has been in operation in our department for over 3 years and has resulted in a demonstrable reduction in cell culture costs and a greater flexibility in the acceptance of skin biopsies for culture.

Ethylmalonic adipic aciduria--a treatable hepatomuscular disorder in two adult brothers.

An adult male presented at 28 years of age with muscle weakness and liver dysfunction. His brother had died suddenly 2 years earlier after presenting with Reyes syndrome. Urine organic acid analysis and muscle and cultured fibroblast fatty acid oxidation studies confirmed a diagnosis of ethylmalonic/adipic aciduria-an inherited defect of fatty acid oxidation. The patient responded favourably to treatment with a low fat/high carbohydrate diet supplemented with riboflavin. This case highlights the importance of considering inborn errors of metabolism, in particular fatty acid oxidation defects, in adults with liver disease, muscle disease or Reyes syndrome.

Measurement of proteinuria

R.H.R. White, Professor of Paediatric Nephrology, The Children’s Hospital, Ladywood Middleway, Ladywood, Birmingham B16 BET (UK) Dear Sir, The recent paper by Chambers et al. [1] highlights the frequency with which gross errors occur in the measurement of urinary total protein concentration in routine hospital laboratories. They argued that the test should be replaced by measurement of albumin and other selected proteins. A variety of nephelometric, turbidimetric, dye-binding and biuret techniques were used and it would have been informative to analyse the results in terms of individual methods. Our experience of measuring total urinary protein concentration by a modification of the Coomassie blue method [2] has proved favourable. We found it highly sensitive at low urinary protein concentrations and reported within-batch coefficients of variation 2.9 amd 0.94% at concentrations of 0.025 and 0.089 g/l, respectively [3]. While the constant relationship which we observed between albumin and total protein excretion in health might alter in disease and become of relevance to those making a special study of glomerular disorders, in clinical practice we have found the measurement of total protein by this method adequate for monitoring progress in our patients. Moreover, the reagents cost less than those of the albumin radioimmunoassay. We expressed our results as protein/creatinine ratios in early morning urine (EMU) samples, and found an extremely good linear correlation with the protein excretion rate in timed, overnight collections [3]. The method proved sufficiently sensitive to detect small but significant changes in proteinuria, consequent upon experimental modulation of dietary protein intake, in patients with reduced functioning renal mass due to reflux ne-phropathy [4]. Moreover, we demonstrated a highly significant correlation between the amount of proteinuria and the extent of segmental glomerulosclerosis in the same condition [5], and concluded that the detection of EMU ‘microproteinuria’ is a simple and reliable way of demonstrating glomerular hyperperfusion. The collection of an EMU specimen is simple and eliminates the inaccuracies created by timing errors and loss of urine; it is therefore particularly valuable for very young children. It is unclear to us why most routine hospital laboratories continue to measure protein excretion in 24-hour collections, as they do not discriminate between postural and pathological proteinuria and cause considerable inconvenience to patients. References Chambers RE, Bullock DG, Whicker JT: Urinary total protein estimation – fact or fiction. Nephron 1989;53:33–36.