146 Glycogen Metabolism in Chorionic Villous Samplings: Possibilities for Prenatal Diagnosis of Glycogen Storage Diseases

Abstract

The ability of the newborn kidney to reabsorp filtered bicarbonate seems to be limited when compared to that of the adult kidney. This may be due to renal or extrarenal factors which are still ill-defined. Bicarbonate handling during acute acid-base changes was studied in newborn rabbits before the end of nephrogenesis. Fourty anesthetized mechanically-ventilated rabbits aged 5-12 days were studied during hypercapnic acidosis, metabolic acidosis or metabolic alkalosis. Inulin was used as a marker of glomerular filtration rate. Control newborn rabbits were in a state of hypochloremic metabolic alkalosis (blood pH 7.49, HCO, 31 mmol/l, CI 83 mmol/l) which was not present in adult rabbits (pH 7.41, HCO, 19.5, CI 100 Various enzymes of which the deficiency causes a type of glycogenoses have been investigated in 20 control samplings of chorionic villi (CVS) between 8 and 12 weeks of gestation. Except glucose 6-phosphatase which is either not expressed or not yet developed, the activity of seven enzymes were well measurable in cvs. The glycogen content was 0.2-0.8 g per 100 g CVS; the activity of 1 ,4-~-glucosidase (4G), 3.0-16.0 nmol/min/mg protein (U); amyloglucosidase (6G), 0.12-0.56 U; brancher, 0.40-0.95 U; phosphorylase (PL), 0.2-1.5 U (a form) or 3.0-15.0 U (total); phosphorylase kinase (PK), 1.3-7.0~mol/min/mg protein; phosphofructokinase (PF), 1.8-8.5 U; glycogen synthase, 0.1-0.3 U (I-form) or 0.4 -3.0 U (D-form). Prenatal diagnosis of M.Pompe was performed in a pregnancy at risk by chorionic biopsy at the 8th week as well as by amnioscentesis at the 17th week. The 4G activity in CVS and in amniotic cells was in the range of heterozygotes, as was in leucocytes of cord blood at birth. Glyocgenosis type III can also' be diagnosed prenatally by direct assay of 6G in CVS. Investigation of PL, PK and PF was done by isoelectrofocusing and kinetic studies in order to explore diagnostic ways of severe forms of respective deficiencies. Three variants of phosphorylase kinase (PK) deficiency have been described, differing from one another by their genetic mode of inheritance and their organ involvement. The present report describes two additional variants for GSD IX: The first, in which the PK deficiency was reduced in muscle only (activity was 0.3 as compared to 2.6±1.5 U phosphorylase a/mg prot/min), with no indication of liver,erythrocyte or leukocyte involvement. The second variant presented in a 2-year-old boy with hepatomegaly and a slight tendency to fasting hypoglycemia. Blood cell PK activities were measured and are summarised in the Spontaneously breathing pre term infants 48 h old, of 32 weeks gestation or less, were assigned randomly to receive caffeine citrate (loading dose 20 mg/kg,' maintenance dose 10 mg/kg/day) or placebo (NaCI 0.9%). To demonstrate a reduction from 50% to 25% in the proportion of infants with >6 hypoxaemias (decrease in tcPo, of 20% within 20 sec)/12 h required a sample size of 25 per group (50% power, 5% type I error). tcPo, was recorded continuously for 50 hand analised by computer....

Diagnosis of glycogen storage disease

“…It would be interesting, however, to study this system in patients with other glycogen storage disease types such as Ic or possibly Id (Nordlie et al, 1983;Burchell et al, 1987). Up to now a fetal liver biopsy has been the only method of prenatal diagnosis of this disease (Gotbus et al, 1988), since no enzyme activity has been measured in culture cells or in chorionic villi (Shin et al, 1986a). The identification and study of the gene responsible for this disease may therefore contribute a major step towards achieving the diagnosis in the fetus.…”