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Glucose metabolism and hypoglycaemia in SIDS
A Burchell1, H Lyall, A Busuttil
1Department of Obstetrics & Gynaecology, Ninewells Hospital, Dundee.
Insights
Infant survival relies on blood glucose control. Defects in glucose-6-phosphatase proteins can lead to fatal hypoglycemia in infants, particularly those at risk for Sudden Infant Death Syndrome (SIDS).
Area of Science:
- Biochemistry
- Pediatric Medicine
- Metabolic Disorders
Background:
- Neonatal survival is critically dependent on mature blood glucose homeostatic mechanisms.
- Failure of these mechanisms or inborn errors of metabolism can cause life-threatening hypoglycemia in infants.
- Environmental stressors can exacerbate underlying homeostatic deficiencies, precipitating hypoglycemia.
Purpose of the Study:
- To investigate defects in carbohydrate metabolism, specifically glucose-6-phosphatase proteins, in infants who died of Sudden Infant Death Syndrome (SIDS).
- To establish a model system for studying glucose-6-phosphatase abnormalities in SIDS cases.
- To explore molecular approaches for predicting and preventing hypoglycemia in at-risk infants.
Main Methods:
- Utilized six microsomal glucose-6-phosphatase proteins as a model system.
- Determined the ontogeny of glucose-6-phosphatase proteins.
- Employed a combination of techniques, including gross pathology and histology, to identify glucose-6-phosphatase abnormalities in SIDS cases.
Main Results:
- Established that intact microsomes from unfrozen liver samples are suitable for studying glucose-6-phosphatase in SIDS.
- Demonstrated abnormalities of glucose-6-phosphatase in SIDS cases.
- Classic pathology has defined subgroups of sudden infant deaths, aiding molecular investigations.
Conclusions:
- Defects in glucose-6-phosphatase are implicated in SIDS cases.
- Understanding these defects is crucial for identifying infants at risk of hypoglycemia.
- Molecular approaches can advance the prediction and prevention of hypoglycemia in vulnerable infants.
Abstract:
Once a child is born its survival depends on the maturation of the blood glucose homeostatic control mechanisms. When this fails or where there is an inborn error of metabolism the infant is susceptible to potentially fatal hypoglycaemic episodes. A variety of environmental stresses, either singly or in combination, such as inappropriate or low caloric intake, acute infections of childhood, endotoxaemia, fever, xenobiotic exposure, oxidative stress or anaphylaxis, can greatly exacerbate the deficiency of the normal homeostatic compensatory mechanism and result in the onset of hypoglycaemia. Various inborn errors have been found in infants who died of SIDS. Our approach to this problem has been to use the six microsomal glucose-6-phosphatase proteins as a model system to study defects in carbohydrate metabolism in cases of SIDS. Initial studies determined the ontogeny of the glucose-6-phosphatase proteins and showed that intact microsomes isolated from unfrozen liver samples can be used to study glucose-6-phosphatase in cases of SIDS that were presumably due to the low concentrations of liver lipid peroxidation. More recently we have used a combination of techniques to demonstrate the abnormalities of glucose-6-phosphatase in cases of SIDS. Classic gross pathology and histology have now clearly defined the various subgroups of sudden and unexpected deaths of infancy. This now enables us to develop new molecular approaches to predict and prevent hypoglycaemia in infants who are at risk of SIDS.