Oddmund Søvik

Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycaemia.

Abstract. A deficiency of extramitochondrial hepatic phosphoenolpyruvate carboxykinase has been demonstrated in a boy with severe, persistent neonatal hypoglycaemia. Hepatic glucose‐6‐phosphatase, fructose‐1.6‐diphosphatase and pyruvate carboxylase were normal. The total activity of phosphoenolpyruvate carboxykinase was also normal, but the enzyme showed an abnormal subcellular distribution, virtually no activity being detected in the extramitochondrial fraction of a liver homogenate. The boy died at the age of 2 years 10 months. Autopsy revealed severe cerebral atrophy, atrophy of the optic nerve, and fatty infiltration of liver and kidney.

X‐linked aqueductal stenosis

A family is reported in which eight members of one generation were affected by the syndrome hydrocephalus with aqueductal stenosis. With the exception of one child who lived for several weeks, they all died at or within 10 days of birth. Autopsy of a pair of affected twins showed marked stenosis of the aqueduct of Sylvius with fusion of the lamina quadrigemina. There were no signs of previous or present inflammatory changes or neo‐plasia. All the affected individuals were males, and the familial and pathological data presented support the concept that aqueductal stenosis in this family was due to an X‐linked gene, and may have a developmental origin.

GLUCONEOGENESIS IN INFANCY AND CHILDHOOD II. Studies on the Glucose Production from Alanine in Three Cases of Persistent Neonatal Hypoglycaemia

Abstract. Gluconeogenesis was studied in 3 cases of persistent neonatal hypoglycaemia. In 2 of the cases the labelling of blood glucose after i.v. injection of 14C‐alanine was reduced. In these 2 patients only 1.3‐5% of the injected radioactivity was recovered in blood glucose, compared with 10% in normoglycaemic patients. The labelling of glucose from 14C‐glycerol, as studied in one case, was not reduced. In this patient the labelling of blood glucose from 15C‐alanine was improved after subtotal resection of the pancreas, and with increasing age. By the time of the isotope studies the plasma insulin was normal in all patients, and no deficiency of glucagon secretion could be detected after stimulation with an alanine load. A quantitative amino acid analysis of plasma revealed a moderate increase of some of the glucogenic amino acids. The results were interpreted as a deficiency of gluconeogenesis, probably at the phosphoenolpyruvate carboxykinase or pyruvate carboxylase step.

ABNORMAL EFFECTS OF PREALBUMIN FROM SERA OF PSYCHOTIC PATIENTS ON METABOLISM OF RAT DIAPHRAGM

It has earlicr been demonstrated that glucose uptake in rat diaphragm is inhibited by sera from schizophrenics (WALAAS, LINGJBRDE et al. 1954). This effect could be attributed to an inhibitory effect by a,-globulin fraction from sera of these patients on glucose uptake in rat diaphragm. (HAAVALDSEN, LINGJBRDE & WALAAS, 1958). I n extensive studies FROHMAN, GOTTLIEB, BECKETT and coworkers a t The Lafayette Clinic, Detroit, have shown that a,-globulin fractions from sera of schizophrenics influences glycolysis of chicken erythrocytes (FROHMAN, GOODMAN, BECKETT, LATHAM, SENF & GOTTLIEB, 1962). I n the present communication it has been reported that prealbumin isolated on starch block electrophoresis from sera of schizophrenic and other psychotic patients influences the metabolism of rat diaphragm. It has been shown that prealbumin from these patients markedly inhibits glycogen synthesis, incorporation of 1%-glucose into glycogen and incorporation of 14C-phenylalanin in proteins of rat diaphragm. This means that the abnormal serum prealbumin inhibits glycogen synthesis as well as protein synthesis in vitro. No such effects of serum prealbumin from normal individuals have been observed. The abnormal multimetabolic effects of prealbumin to a great extent disappeared upon treatment of the patients with chlorpromazine. We consider the abnormalities in serum protein fractions which have been demonstrated may be responsible for abnormalities in carbohydrate metabolism seen in schizophrenia (LINGJXRDE, 1964), and may also be related to psychotic exacerbations in the disease. A report on these investigations will appear elsewhere.

Ketotic hypoglycemia in a four-year-old boy with adrenal cortical insufficiency.

Ulstrom and associates have described a syndrome of sporadic and symptomatic hypoglycemia associated with ketosis in children (3). Episodes of hypoglycemia could be provoked by feeding a low-calorie diet, and were characterized by a failure to respond to glucagon. This type of hypoglycemia usually occurred after infancy and in children with a history of low birth weight. Approximately half of the children with idiopathic hypoglycemia were of the ketotic type. Grunt et al. (9), studying eight children with ketotic hypoglycemia, added the following characteristics: a stormy perinatal course, a marked variability in blood sugar levels during a 12-hour fast, and rapid utilization of glucose despite normal to low levels of serum insulin. The pathogenesis of this disorder is, however, still obscure, and the existence of this disease entity is questioned by the work of Senior & Loridan (16). In the latter study the affected children as well as the control subjects developed hypoglycemia in response to a ketogenic diet. In pituitary insufficiency the association of hypoglycemia and ketonuria has been observed (15, 17). We here report on a case of ketotic hypoglycemia, in which the diagnostic work-up revealed a primary adrenal cortical insufficiency (Addison’s Disease). METHODS