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At least 1,225 records · Page 68Linked to original sources
PubMed1978

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.

Cells, Cultured↗
PubMed1978

Prenatal and postnatal diagnostic difficulties in a family with rare alleles of the galactose-1-phosphate uridyl transferase locus.

Whole-blood galactose-1-phosphate uridyl transferase (Gal-PUT) (EC 2.7.7.12) activity was absent in a newborn boy with galactosaemic symptoms. The symptoms disappeared on a galactose free diet. In the next pregnancy prenatal diagnosis was performed. Gal-PUT activity was measured by isotope technique and Gal-PUT genotype was determined by gel electrophoresis. The mother was shown to be heterozygous Duarte/heterozygous Los Angeles, the father heterozygous Duarte/heterozygous galactosaemia. The fetus had the same genotype as the father. A normal girl without galactosaemic symptoms was born. Reinvestigation of the index case showed that he was also heterozygous Duarte/heterozygous galactosaemia. It is concluded that the activity of Gal-PUT should always be measured by isotope technique to prove the diagnosis of heteditary galactosaemia. Furthermore, Gal-PUT-genotyping in families with rare alleles is essential for safe prenatal diagnosis.

Alleles↗
PubMed1986

Development of a protocol for newborn screening for disorders of the galactose metabolic pathway.

The protocol evaluated in this paper employs an enzymatic assay of galactose metabolites, thin layer chromatography, and an assay of galactose-1-phosphate uridyl transferase on a single sample of blood collected routinely for newborn screening. Its effectiveness was tested by a retrospective study of known galactosemic blood samples, and also by a prospective study of 207,000 newborn samples from which 6 infants with severe transferase deficient galactosaemia and 2 infants with red cell epimerase deficiency were identified. The detection rate for severe transferase deficiency in the newborn population was 1:35,000. Advantages include low false positive rate, definitive diagnosis within 6 hours of sample receipt, and the use of technically simple and robust procedures. This protocol overcomes the difficulties encountered with previously described procedures.

Australia↗
PubMed1978

Inhibition of glycolysis by L-sorbose in dog erythrocytes.

We have demonstrated previously that in vitro L-sorbose acts directly on dog erythrocytes to induce hemolysis. Here we report that L-sorbose depresses lactate formation in dog hemolysates from glucose, mannose and fructose but not from glucose-6-phosphate and galactose, suggesting that L-sorbose interacts with glycolysis at the level of the hexokinase.

Animals↗
PubMed1996

Three missense mutations in the galactose-1-phosphate uridyltransferase gene of three families with mild galactosaemia.

UNLABELLED: Classical galactosaemia caused by deficiency of galactose-1-phosphate uridyltransferase (GALT) is characterized by acute symptoms of hepatocellular dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation reverses these complications immediately, however, most of these children have a long-term complication of verbal dyspraxia mental retardation and ovarian failure. The GALT gene was cloned and several mutations including the common Q188R have been reported. In this study the coding region of GALT was amplified by polymerase chain reaction from genomic DNA of classical galactosaemic individuals and characterized by direct sequencing of the products. Three missense mutations were identified in three patients with a mild galactosaemic variant: (1) replacement of threonine-138 by methionine (T138M); (2) replacement of arginine by tryptophan (R259W); and (3) replacement of threonine by alanine (T350A). All three galactosaemic individuals, one girl and two boys, have varying degrees of residual GALT activity in RBC and their galactose-1-phosphate levels decreased much faster than in other galactosaemic patients. These missense mutations occur in regions that are not highly conserved domains. CONCLUSION: The study of the molecular basis related to the phenotype variation may indeed help to prognosticate the outcome of patients with classical galactosaemia.

Amino Acid Sequence↗
PubMed1993

Hypergalactosaemia in a patient with portal-hepatic venous and hepatic arterio-venous shunts detected by neonatal screening.

Hypergalactosaemia was discovered in a newborn girl during routine metabolic screening. Hereditary enzyme deficiency was ruled out. She had multiple hepatic haemangiomas with portal-hepatic venous and hepatic arterio-venous shunts. Since she showed signs of high-output heart failure due to the arterio-venous shunt, hepatic artery embolization was performed at age 3 months. A galactose tolerance test was performed before and after embolization and when the haemangioma no longer appeared on ultrasonography. Even after embolization, the level of blood galactose was abnormally elevated in the galactose tolerance test, but the blood galactose was eliminated more rapidly than before embolization. When the hepatic haemangioma was no longer detected by ultrasonography, the peak galactose level decreased. We surmise that the hypergalactosaemia was due to these shunts. In cases of hypergalactosaemia of unknown cause; liver haemangioma with portal-hepatic venous shunting should be considered as a possible cause. If a hepatic arterio-venous shunt also exists, this may contribute to the effect of the portosystemic shunting.

Arteriovenous Malformations↗
PubMed1992

Hypergalactosaemia and portosystemic encephalopathy due to persistence of ductus venosus Arantii.

Hypergalactosaemia was discovered in a newborn girl during routine metabolic screening. Hereditary enzyme deficiency was ruled out. Because hypergalactosaemia persisted, an open ductus venosus Arantii was suspected but remained undetected by conventional two-dimensional ultrasonography. It was demonstrated by combined colour and pulsed wave Doppler sonography. At age 3 years 6 months, the girl developed initial symptoms of portosystemic encephalopathy which progressed and was treated by protein restriction, oral lactulose and flumazenil, with some success. In the absence of enzyme deficiency, hypergalactosaemia in the newborn is an early sign of duct persistence. For the unambiguous diagnosis of an open duct, colour Doppler sonography is the method of choice. Pulsed wave Doppler sonography is recommended for pathophysiological characterisation of the splanchnic venous return.

Abnormalities, Multiple↗
PubMed1992

Patent ductus venosus with hypoplastic right hepatoportal system in a young child born with asymmetric intra-uterine growth retardation.

We report a functioning ductus venosus with hypoplasia of the right hepatoportal system in a 2-year-old child born with asymmetric intra-uterine growth retardation. Postprandial galactosaemia and hyperammonaemia were clues to diagnosis of portal-systemic shunt through the patent ductus venosus, which was confirmed by ultrasonography and angiography.

Abnormalities, Multiple↗
PubMed1986

Oral intake of glucose plus galactose and erythrocyte galactose-1-phosphate. A nutritional evaluation of hydrolyzed lactose.

This study deals with the metabolic effects of hydrolyzed lactose: After an overnight fast 5 healthy adult volunteers consumed a glucose-galactose mixture equivalent to 61.4 g of lactose (or 125 g of a dried skim milk powder with hydrolyzed lactose). The postprandial rise of erythrocyte galactose-1-phosphate (gal-1-P) never exceeded 22.3 mumol per liter packed red blood cells. This amounts to no more than 22% of the levels known from galactosemic children to be safe, concerning ocular, neural or hepatic damage. We conclude that the consumption of the hydrolyzed lactose does not cause a risk for consumer's health as judged from this galactose metabolite. A considerably higher risk, however, may accompany the consumption of galactose alone which causes around 17-fold higher plasma galactose levels and around 8-fold higher erythrocyte gal-1-P concentrations for more extended time periods.

Adult↗
PubMed1993

Long-term outcome in 134 patients with galactosaemia.

In a retrospective study 134 galactosaemic patients, born between 1955 and 1989 in the Federal Republic of Germany were traced and their long-term outcome evaluated. We investigated 83 galactosaemic patients (78 homozygotes, 5 compound heterozygotes) by clinical, psychometric and laboratory testing; 31 patients were evaluated by medical history, the remaining 20 patients had died due to sequelae of the underlying disease. In 48 out of 78 classical galactosaemia patients galactose-free therapy had been started before the 15th day, in 19 between days 15 and 56 and in 11 patients after the 56th day. Physical findings revealed that puberty was delayed in 1 out of 18 males and 6 out of 11 females. Neurological abnormalities included ataxia (n = 6), intention tremor (n = 11) and microcephaly (n = 10). Speech abnormalities were found in 43 out of 66 patients over 3 years of age and disturbance of visual perception and/or arithmetic deficits in 29. Intelligence declined with age, i.e., a DQ or IQ less than 85 was found in 4 out of 34 patients less than 6 years of age (12%), in 10 out of 18 between 7 and 12 years (56%) and in 20 out of 24 older than 12 years (83%). Metabolite patterns (RBC galactose-1-phosphate and UDP-galactose, plasma and urinary galactitol) did not correlate with DQ or IQ. Dietary compliance was good in almost all patients. Compound heterozygotes (n = 5) had normal mental and growth development and all laboratory parameters were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Gonadal function in galactosemics and in galactose-intoxicated animals.

Gonadal dysfunction, specifically hypergonadotropic hypogonadism, in female galactosemics is an almost universal finding. Minimal transferase activity may modulate ovarian function and the time of menopause. In contrast, male galactosemics have a relatively low risk of gonadal dysfunction. Animal models have variously suggested prenatal and postnatal insults which may play a role in the gonadal pathology. Several candidate toxic states may be involved. Current dietary restrictions are inadequate to prevent ovarian failure. Until such time as the pathophysiology is better understood, therapy will remain palliative and supportive. Exogenous estrogen and progesterone have roles in assisting pubertal changes and in prevention of the sequelae of a post-menopausal state.

Animals↗