Impairment of the activity of the hepatic microsomal glucose‐6‐phosphatase system in three preterm infants

Abstract

Three preterm infants born at 26-30 weeks' gestation who died between 103 and 266 days after birth were found to have elevated hepatic glycogen levels. Kinetic analysis of the hepatic microsomal glucose-6-phosphatase system demonstrated that one infant had abnormally low levels of activity of the glucose-6-phosphatase enzyme (partial type 1a glycogen storage disease) and two had deficiencies of T2, a microsomal phosphate/pyrophosphate transport protein (type 1c glycogen storage disease). In all three cases glycogen storage disease was not suspected prior to death even though both hypo- and hyperglycaemic episodes were recorded in the first 15 days after birth indicating that they had somewhat disordered blood glucose regulation. In the infant with low glucose-6-phosphatase enzyme activity, abnormal development of the glucose-6-phosphatase enzyme cannot be ruled out. This is the first description of abnormalities in the glucose-6-phosphatase system in preterm infants.

Therapeutic insulin and hepatic glucose-6-phosphatase activity in preterm infants

“…Hypoglycaemia is associated with cerebral damage in infants,1 2 31 and in situations in which hepatic glucose-6-phosphatase activity is low—for example, in type I glycogen storage disease6—episodes of low blood glucose are common. Hepatic glucose-6-phosphatase activity is also low in preterm infants,14 15 18 and episodes of hypoglycaemia are common 23 16 The most likely explanation for most episodes of low hepatic glucose-6-phosphatase activity in preterm infants is delayed or abnormal postnatal development of enzyme expression.…”

The human embryonic-fetal kidney endoplasmic reticulum phosphate-pyrophosphate transport protein

“…In addition, we have described three preterm infants who died and on analysis of hepatic autopsy samples, one was found to have abnormal glucose-6-phosphatase enzyme and two to have no T215 transport capacity [20]. In one of the T2lS-deficient infants, a renal autopsy sample showed T215 deficiency [20].…”

“…In addition, we have described three preterm infants who died and on analysis of hepatic autopsy samples, one was found to have abnormal glucose-6-phosphatase enzyme and two to have no T215 transport capacity [20]. In one of the T2lS-deficient infants, a renal autopsy sample showed T215 deficiency [20]. In view of the fact that we have subsequently shown that developmental disorders of this enzyme system are common [19], it is likely that these two cases of T2~ deficiency have a developmental rather than genetic basis.…”

Regulation of liver glucose production

“…In most (but not all) term infants glucose‐6‐phosphatase activity increases dramatically at birth reaching adult levels within approximately 2 days 4 . In contrast, in many preterm infants, activity does not increase postnatally (or the rise is very blunted) and can remain low for several months 5 , 6 . This persistence of the fetal state of expression in preterm infants, where glucose‐6‐phosphatase activity is low but the protein is normal, is a developmental disorder and a failure of perinatal regulation 5 …”

“…Genetic deficiencies in the glucose‐6‐phosphatase enzyme and the endoplasmic reticulum glucose‐6‐phosphate transport protein occur in both term and preterm infants, but these disorders are distinct from the developmental disorders above 1 , 6 , 7 . Infants with either genetic deficiencies or developmental disorders of this system are susceptible to episodes of hypoglycaemia that if severe can lead to brain damage or even death.…”