1/4. Possible galactosaemia in an Ethiopian: case report.Galactosaemia should be considered in any infant who presents with cholestatic jaundice in early infancy, particularly in the face of previous neonatal deaths. Newborn screening programmes would have been ideal in early detection of the cases. The clinical manifestation, the urine test for reducing sugars and the amelioration of clinical features after 'milk-withdrawal' are quite indicative of the disease in centres where enzyme assays cannot be performed. Elimination of milk and milk products as well as other lactose containing sources from diet, secures an excellent outcome, provided that it is initiated early in life.- - - - - - - - - - ranking = 1keywords = programme (Clic here for more details about this article) |
2/4. Biochemical studies of a human low-activity galactose-1-phosphate uridyl transferase variant.A low activity galactose-1-phosphate uridyl transferase (transferase) variant in a newborn infant has been demonstrated by biochemical studies in erythrocytes and cultured skin fibroblasts. The newborn infant was a galactosaemic suspect identified in a neonatal metabolic screening programme. On breast feeding, he did well without clinical symptoms of galactosaemia during the first 15 days of life. However, substantial amounts of erythrocyte galactose-1-phosphate and urinary galactitol corresponding to the levels in untreated galactosaemic patients, along with mild amino aciduria, were found. The transferase activity, as measured by a sensitive micro kinetic radioisotopic method, was about 7--10% of the normal. On starch gel electrophoresis, the enzyme from the haemolysate had similar mobility as the normal in Tris--glycine buffer, pH 8.8 and phosphate buffer, pH 7.0, but had a slower mobility than that of the normal in the histidine buffer, pH 7.8. The mobility difference was much clearer in a semipurified enzyme preparation. The transferase enzyme in the haemolysate appeared to be more heat labile.- - - - - - - - - - ranking = 1keywords = programme (Clic here for more details about this article) |
3/4. Galactosaemia: case for neonatal screening illustrated by recent Australian experience.The varied presentation and clinical features of classical galactosaemia are illustrated by the case histories of seven babies born in western australia since January, 1962, and of two babies born in south australia in whom diagnosis was made as a result of adding galactosaemia to the Guthrie screening programme in October, 1974. All were shown to have a severe deficiency of galactose-1-phosphate uridyl transferase in their red blood cells. We compare our findings with those in 10 galactosaemic babies born in victoria over a similar period, and show that in both groups these were two main modes of onset: acute and insidious. jaundice and escherichia coli infection were prominent in the 13 babies with an acute onset of galactosaemia, while poor weight gain, intermittent vomiting and cataracts were features of the five babies with an insidious onset. An enlarged liver was usually found in both groups. We discuss the various approaches to neonatal screening of galactosaemia in the light of experience in massachusetts and south australia. The use of cord blood can be expected to lead to diagnosis before babies with acute onset become ill, while the use of blood collected at five days for the Guthrie test avoids the collection of another routine sample for a relatively rare disorder. The result of red cell transferase assays of parents and siblings of our patients are discussed in relation to their implication for genetic counselling. The relevance of antenatal diagnosis to the prevention of possible intrauterine damage to an affected fetus is pointed out.- - - - - - - - - - ranking = 1keywords = programme (Clic here for more details about this article) |
4/4. Molecular characterization of a unique patient with epimerase-deficiency galactosaemia.Inherited deficiencies of UDP-galactose 4-epimerase (GALE) have been associated with two distinct phenotypes. The vast majority of North American patients are clinically asymptomatic, are identified through newborn screening programmes for classical galactosaemia, and are of African-American descent. At least two symptomatic patients have been reported, one Pakistani and the other Asian Muslim, both with severe complications in the neonatal period and subsequent mental retardation. Through newborn screening, we have identified a GALE-deficient patient who is of mixed Pakistani/caucasian ancestry. He was clinically well in the neonatal period on a lactose-containing diet, and biochemical studies, including urine reducing sugars and galactitol, were consistent with a diagnosis of peripheral GALE deficiency. Although early developmental milestones were met normally, he now shows significant developmental delays in both motor and language skills. Mutational analysis revealed this patient to be a compound heterozygote at the GALE locus, with mutations N34S and L183P identified in the patient and confirmed in the parents. This report represents the first characterization of specific mutations in a GALE-deficient patient in conjunction with biochemical and clinical phenotype, and facilitates further studies of the GALE enzyme and its role in the different clinical forms of epimerase-deficiency galactosaemia.- - - - - - - - - - ranking = 1keywords = programme (Clic here for more details about this article) |