J. T. Allen

The investigation of UDPGlucose and UDPGalactose concentration in red blood cells of patients with classical galactosaemia.

UDPGlucose (UDPGlc) and UDPGalactose (UDPGal) are nucleotide sugars formed via the galactose metabolic pathway and are essential cofactors for the incorporation of galactose and glucose into complex glycoproteins and glycolipids. It has been proposed that in classical galactosaemia, where the enzyme galactose-1-phosphate uridyl transferase is deficient, the reaction product UDPGal is reduced leading to the long-term complications associated with the disease. We have measured the concentration of UDPGal and UDPGlc in red blood cells by high performance liquid chromatography (HPLC) in 16 children and 15 adult galactosaemics and compared the results with 30 and 27 control children and adults, respectively. The results indicate that UDPGal levels were found to be significantly reduced in galactosaemic patients and UDPGlc/UDPGal ratios significantly increased.

A Method of Assessing Amniotic Fluid Lecithin Concentrations and Predicting Foetal Lung Maturity, by Estimating Total Palmitic Acid Concentration Using G.L.C.

A rapid G.L.C. method for estimating total palmitic acid in amniotic fluid is described and it is shown that the principal source of this substance is lecithin. Thus, the technique is a convenient means of assessing amniotic fluid lecithin concentrations and of predicting the maturity of the foetal lung.

UDP-glucose and UDP-galactose concentrations in cultured skin fibroblasts of patients with classical galactosaemia

SummaryA very clear-cut reduction in UDP-galactose (UDPGal) levels in erythrocytes, skin fibroblasts and liver of patients with classical galactosaemia has been reported. As UDPGal is the galactosyl donor in glycoprotein and glycolipid synthesis, it has been suggested that an abnormality in these complex compounds may be the cause of some of the long-term complications of the disease. More recent work on erythrocytes, employing mainly HPLC rather than the enzyme methods used to measure UDPGal originally, casts doubt on the hypothesis because, although some reduction was still found, there was a large overlap between galactosaemic and normal distributions. We have reproduced the experiments on cultured skin fibroblasts at confluency, but measuring UDPGal and UDP-glucose (UDPGlc) by HPLC. There was no reduction in UDPGal levels in galactosaemic compared to control cell lines. The existence of a biologically significant depletion of UDPGal in galactosaemia remains in doubt.

Gas-liquid chromatographic determination of galactitol in amniotic fluid for possible use in prenatal diagnosis of galactosaemia

A gas liquid chromatographic method for the estimation of galactitol in amniotic fluid from pregnancies at risk for galactosaemia is described. The method is based on the almost complete removal of glucose from the amniotic fluid by ion exchange, and the subsequent chromatography of galactitol as its hexaacetate.

Prenatal Diagnosis of Disorders of Galactose Metabolism

SummaryOf three clinically significant galactose disorders, there is only a real need and experience of prenatal diagnosis in classical galactosaemia. Prenatal diagnosis for this disorder may be carried out by galactose-1-phosphate uridyl transferase assay in cultured amniotic fluid cells or in chorionic villus biopsies and by galactitol estimation in amniotic fluid supernatant. Although the long-term outcome of patients treated on a galactose-restricted diet is recognized to be unsatisfactory, prenatal diagnosis is only rarely performed with a view to terminating the affected pregnancy.

Arginosuccinate synthetase deficiency: good outcome despite severe neonatal hyperammonaemia

obtained for organic acid analysis. The patients psychomotor development, tested by Bayleys scale, was found to be slightly retarded. An EEG showed paroxysmal abnormalities. Neurosensory hearing loss and optic atrophy were not found, but visual evoked potentials showed prolonged latencies. The biotin dose was gradually decreased to 5 mg/day. One month later, she was healthy with no respiratory and cutaneous manifestations. Our experience, combined with the other reports, indicates that biotinidase deficiency should be included in the differential diagnosis of unexplained respiratory problems.

Comparison of amino acid concentrations in amniotic fluid from fetal neural tube defective and normal pregnancies

Amniotic fluid collected during the second trimester of pregnancy was analysed for amino acid and protein concentrations. The composition of amniotic fluid from pregnancies complicated by fetal anencephaly or spina bifida was investigated for variance from normal amniotic fluid. In spina bifida the hydroxy amino acids were raised whilst the branched chain amino acids were lower in concentration. In anencephaly the total amino acid and the protein concentrations were raised, and a wider range of concentrations for most of the amino acids was apparent.

Benign methylmalonic acidemia in a sibship with distal renal tubular acidosis.

Abstract. Two male infants born to consanguineous parents were investigated for feeding difficulties in the 1st month of life. Both were found to have distal renal tubular acidosis (dRTA) with hypercalciuria. Nephrocalcinosis was present in the first child but not in the second. Urinary organic acid profile demonstrated an excess of methylmalonic acid (MMA) in both children in the absence of any other organic acid. MMA mutase activity and propionate incorporation were normal. There have been no neurological symptoms in either child. The first child has normal growth and psychomotor development at 4 years. His brother, who also has significant gastro-oesophageal reflux, has failed to thrive and currently requires nasogastric feeding and caloric supplements to maintain weight along the 3rd percentile. Urinary and plasma MMA continue to be raised in both cases. The association of increased urinary and plasma MMA and dRTA presenting in the 1st month of life has not previously been reported and may represent a new syndrome of autosomal recessive inheritance.