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O Søvik

Publications and source records attributed to O Søvik.

At least 55 records · Page 3Linked to original sources
PubMed1993

Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency: an inborn error of isoleucine and ketone body metabolism.

A review is presented of 22 published cases of verified or probable mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency, a disorder of isoleucine and ketone body metabolism. The clinical expression, characterized by ketoacidosis, vomiting and lethargy, is highly variable. Typical age of onset is between 6 and 24 months. The disorder, which has been observed in several ethnic groups, is apparently inherited as an autosomal, recessive trait. The prognosis is relatively good if acute episodes of ketoacidosis and dehydration are adequately treated. There is abnormal urinary excretion of 2-methyl-3-hydroxybutyric acid, tiglylglycine, and in some instances also 2-methyl-acetoacetic acid. However, such a pattern of organic aciduria has also been found in cases with normal thiolase activity. Genetic complementation analyses have demonstrated considerable heterogeneity. The cDNA for human methyl-acetoacetyl-CoA thiolase has been cloned and sequenced. Studies in one patient showed a G-to-A substitution at position 1138 of the mRNA, causing 347Ala to Thr change in the mature enzyme. Studies in other patients have shown variable enzyme amount and/or stability.

Acetyl-CoA C-Acyltransferase↗
PubMed1992

[Insulin pen in the treatment of childhood diabetes].

37 diabetic children changed from insulin syringes, with individually adapted mixtures of rapid and intermediate acting insulin, to a regimen involving use of an insulin pen (Insuject, Novo Nordisk, Copenhagen) and standard insulin mixtures. During the study an attempt was made to arrive at an optimal regimen for each child by selecting from among the following available insulin preparations (proportion rapid/intermediate acting in parentheses): Velosulin (100/0), Initard (50/50), Mixtard (30/70), Combitard (15/85), and Insulatard (0/100). The 35 families who completed the one-year study maintained that the Insuject pen made the injection procedure much easier. The pen proved to motivate the children to perform the injection without help. No effort was made to increase the number of daily injections, but seven families changed from two to three daily doses on their own initiative. The HbAlc at zero, three, six, nine and 12 months were as follows (SD in parentheses): 7.5 (1.2); 7.9 (1.5); 7.6 (1.2); 7.8 (1.4); and 7.9 (2.1). We conclude that the Insuject insulin pen is a safe and reliable instrument in childhood diabetes. Good metabolic control can be obtained with commercial insulin mixtures given 2-3 times daily.

Child↗
PubMed1992

A coupled assay detecting defects in fibroblast isoleucine degradation distal to enoyl-CoA hydratase: application to 3-oxothiolase deficiency.

We developed a coupled NaH14CO3 fixation assay to detect 3-oxothiolase deficiency in extracts of cultured human fibroblasts. Cell extracts were incubated with tiglyl-CoA, NAD, CoASH, ATP and NaH14CO3. The enzymatic activities of tiglyl-CoA (enoyl-CoA) hydratase, 2-methyl-3-hydroxybutyryl-CoA dehydrogenase and 2-methylacetoacetyl-CoA thiolase (3-oxothiolase) were coupled to produce propionyl-CoA. Propionyl-CoA produced in the assay was estimated by fixation of NaH14CO3 into [14C]methylmalonyl-CoA employing endogenous propionyl-CoA carboxylase. The control activity was 32 +/- 23 pmol/min per mg protein (+/- 1 S.D., range 7-94; 28 cell lines). Five known cases of 3-oxothiolase deficiency had a mean activity of 2% of the control; a sixth case of 3-oxothiolase deficiency was significantly higher at 27% of the mean control value. Coupled assay activity was also low (3% of control) in the cells from a patient with propionyl-CoA carboxylase deficiency.

Acetyl-CoA C-Acetyltransferase↗
PubMed1991

[Diabetes mellitus in children under 2 years of age].

We studied the clinical course in 18 children who were admitted to our department during the time period 1973-87 for onset of diabetes mellitus before two years of age. During these years a total number of 242 diabetics (0-14 years) were admitted from a population of approximately 100,000 children. The 18 cases showed a sex ratio (female/male) of 12/6. In nine cases the duration of symptoms before admittance to hospital was one week or less. The onset of the disease showed no particular seasonal pattern. 13 patients presented with a blood glucose of 25 mmol/l or more. Severe ketoacidosis was observed in nine patients. None of the patients exhibited any well-defined remission period. In the course of the disease, 11 patients had frequent hypoglycemic episodes, nine patients had convulsive attacks, poor metabolic control was evident in five cases, and major psychological problems were frequently encountered. In conclusion, diabetes mellitus in small children can be extremely difficult to manage, both from a medical and a psychosocial point of view. All efforts should be made to support the families of children with this disease.

Age Factors↗
PubMed1991

The incidence of type 1 (insulin-dependent) diabetes mellitus 15-29 years in Norway 1978-1982.

All new cases of Type 1 (insulin-dependent) diabetes mellitus in the 15-29 year age group during the five-year period 1978-1982 were registered using a retrospective technique on a nation-wide basis. A total of 784 newly diagnosed cases were detected, from an average population of 926,192. The degree of ascertainment was almost 90%. The mean yearly incidence for the five-year period was 17.0 per 100,000. The observed incidence is doubled compared to the incidence found in the city of Oslo during the years 1956-1964 (8.8 per 100,000). The male incidence exceeded the female incidence by 12% (p less than 0.05). There was a marked geographic variation in incidence, with a higher incidence in the three southern health regions compared to the two northern, 18.3 vs 13.9 per 100,000 (p less than 0.01). There was a significant seasonal trend in the incidence data (p less than 0.025) with the highest number of new cases detected in the months of January and September and the lowest number in July. In conclusion, the study suggests a two-fold increase of incidence of diabetes mellitus in the age group 15-29 years during the last 2-3 decades and a geographic variation in incidence within the country, pointing to the operation of environmental pathogenic factors.

Adolescent↗
PubMed1991

Binding of insulin and insulin-like growth factor I in bovine chromaffin cells in primary culture.

1. Insulin and insulin-like growth factor I (IGF-I) receptors were studied in bovine chromaffin cells isolated from the medulla by collagenase digestion and kept in primary culture. 2. Specific 125I-labelled insulin binding increased with time in culture with no significant change in the dissociation constant, Kd approximately 0.3 nM. Insulin was nearly 100-fold more potent than IGF-I in displacing 125I-labelled insulin. 3. Affinity crosslinking and SDS gel electrophoresis revealed increased binding of 125I-labelled insulin and 125I-IGF-I with time in culture, the densities of the labelling indicating relatively a much higher expression of IGF-I than insulin receptors in the cells. The apparent molecular weight of both the hormone binding subunits were 135,000, suggesting that the insulin and IGF-I receptors in the adrenal medulla are of the peripheral types. 4. Both receptors thus appeared to be affected by the collagenase treatment but with a subsequent recovery when cells were kept in culture.

Adrenal Medulla↗
PubMed1990

Hereditary tyrosinemia of chronic course without rickets and renal tubular dysfunction.

Three patients with hereditary tyrosinemia type 1, two brothers and one girl, studied at the age of 5, 12 and 15 years, respectively, had neither generalized hyperaminoaciduria, glucosuria nor clinical symptoms of rickets. Untreated the elder brother had only slightly elevated plasma tyrosine level (141 mumol/l, normal less than 80), and low excretion of p-hydroxyphenyllactate. He presented with pronounced thrombocytopenia (3 X 10(9)/l). At 13 years of age he contracted hepatocellular carcinoma. The younger brother presented with serum tyrosine of 318 mumol/l and thrombocyte count 48 X 10(9)/l. Succinylacetone in urine was elevated in both, 30 and 79 mumol/mmol creatinine, respectively. The female patient was investigated for hepatomegaly in infancy, atypical tyrosinemia being considered, but afterwards developed normally without diet or any other treatment until she contracted hepatoma at the age of 15 years. Her plasma tyrosine level was 600-700 mumol/l, and she excreted large amounts of p-hydroxyphenyllactate. Succinylacetone in urine was low but elevated (8 mumol/mmol creatinine). The fumarylacetoacetase activity in fibroblasts from the brothers and in lymphocytes from the girl was less than 5% and 10% of control levels, respectively. In conclusion, the chronic form of hereditary tyrosinemia may occur without evidence of renal tubular dysfunction.

Adolescent↗
PubMed1990

3-Oxothiolase activities and [14C]-2-methylbutanoic acid incorporation in cultured fibroblasts from 13 cases of suspected 3-oxothiolase deficiency.

Cultured fibroblasts from 13 patients with organic aciduria suggesting 3-oxothiolase deficiency were studied by measuring first the capacity of the isoleucine degradative pathways in whole cells, as the incorporation of 1-[14C]-2-methylbutanoic acid into macromolecules, and, second, the activity of 3-oxothiolase in cell homogenates using specific 3-oxoacyl-CoA substrates to identify the different enzymes. Nine patients showed low incorporation by the macromolecular labeling assay, as well as deficiency of 2-methylacetoacetyl-CoA thiolase. In this group of patients, low activity by the macromolecular labeling assay was associated with clinically severe symptoms, and vice versa. Two patients showed reduced macromolecular labeling, but apparently normal 3-oxothiolase. Finally, two patients showed normal activities by either test, the reason for their particular organic aciduria being unknown. In conclusion, occurrence of urinary 2-methyl-3-hydroxybutyric acid and/or tiglyglycine is not an unequivocal indicator of the absence of the thiolase that metabolizes 2-methylacetoacetyl-CoA. Measurement of 1-[14C]-2-methylbutanoic acid incorporation in cultured fibroblasts adds important information in studying possible defects of the isoleucine catabolic pathway.

Acetyl-CoA C-Acyltransferase↗
PubMed1989

[Metabolic diseases causing acidosis in the neonatal period].

The diagnosis of metabolic diseases during the newborn period is difficult because symptoms and findings are similar to those generally encountered in newborn babies who are ill. Moreover, metabolic diseases are often complicated by infections and cerebral hemorrhages. The article presents a short clinical review of metabolic diseases associated with metabolic acidosis in the newborn and discusses appropriate investigations and differential diagnoses. It is important to remember the possibility of metabolic diseases as the cause of metabolic acidosis in the newborn period.

Acidosis↗
PubMed1989

Increasing incidence of diabetes mellitus in Norwegian children 0-14 years of age 1973-1982.

A retrospective technique was used to register all newly diagnosed cases of diabetes mellitus in Norwegian children 0-14 years of age during the ten-year period 1973-1982. A total of 1,914 newly diagnosed cases were detected, from an average population of 932,037 children. The degree of ascertainment was near to 99%. The male incidence exceeded the female incidence by 12% (p less than 0.02). The mean yearly incidence for the ten-year period was 20.5 per 100,000. Comparing the two five-year periods 1973-1977 and 1978-1982, the mean yearly incidence increased from 18.5 to 22.7 per 100,000 (p less than 0.0001). There was a marked geographic variation with the highest incidence in the south-east and lower incidence in the northern part of the country. However, in the northern part of the country, there was a remarkable increase of the annual incidence from the first to the second five-year period (12.9 vs 19.3 per 100,000). The highest numbers of new cases were detected in the months of January and October, and the lowest numbers in May and July. The seasonal pattern was significantly different from a uniform distribution of new cases throughout the year (p less than 0.001). The age-specific incidence increased towards a peak at 12 years for both sexes. In conclusion, Norway has a high and apparently increasing incidence of childhood diabetes. The geographic variation and secular trend present challenging clues for a search of etio-pathogenic factors.

Adolescent↗
PubMed1989

Maturity-onset diabetes of the young. Studies in a Norwegian family.

A Norwegian family showed 20 cases of verified or suspected diabetes in 5 generations, 13 being females and 7 males. In 12 patients the diagnosis was established at 26 years of age or earlier. Fourteen patients were definitely non-insulin-dependent. A high frequency of severe diabetic ophthalmopathy was noted, five patients were blind, two had proliferative retinopathy, and one simplex retinopathy and cataract. Five patients from the last 3 generations were islet cell antibody negative and C-peptide positive. In selected patients the serum insulin response to oral glucose was markedly reduced. HLA determinations in these patients showed absence of DR3 and DR4, and presence of DR2. The inheritance of diabetes in this family is compatible with an autosomal, dominant trait, and the majority of cases fulfilled the criteria of maturity-onset diabetes of the young. The high frequency of severe ophthalmopathy underscores that this disease may have an unfavourable evolution.

Adolescent↗
PubMed1989

Inborn errors of amino acid and fatty acid metabolism with hypoglycemia as a major clinical manifestation.

During the last decade it has become increasingly clear that severe hypoglycemia may be caused by specific enzymatic defects of amino acid and fatty acid metabolism. Several reports have presented hypoglycemic syndromes with reduced fatty acid transport or oxidation, decreased ketogenesis, or abnormalities of the Krebs cycle and electron transport chain. It is of particular interest that several enzymatic defects here discussed may present as Reye's syndrome. An intriguing fact is a highly variable clinical presentation, even in the presence of well-defined enzyme deficiencies. Some patients are desperately ill in the newborn period, whereas in other cases there are symptoms only during catabolic phases later in childhood. The presence of hypoglycemia may be related to low levels of acetyl CoA, with consequently reduced gluconeogenesis; alternatively the glucose-sparing effect of ketones is lost in states of reduced ketone body production. Treatment with pharmacological doses of vitamins may be attempted, depending upon the established or suspected diagnoses. With manifest hypoglycemia i.v. glucose infusion is the treatment of choice. By such means convulsions, and brain damage may be prevented.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

Characterization of specific insulin binding sites on chromaffin cells from bovine adrenal medulla.

1. Insulin receptors were investigated in isolated chromaffin cells from bovine adrenal medulla. 2. The cells were incubated with [125I]insulin in HEPES buffer, pH 7.8 at 15 degrees C for 180 min to obtain steady state binding. Specific binding was linearly related to the number of cells in the range 0.5-10 x 10(6) cells/ml. Insulin and proinsulin caused half maximal displacement of specifically bound tracer in concentrations of 0.18 and 2.46 nM, respectively. 3. Computer analysis of the binding data gave a linear Scatchard plot, consistent with a single class of non-interacting receptors with an affinity constant of 5.6 nM-1, the total number of receptors per cell being 1700. 4. The apparent MW of the insulin binding subunit of the receptor was 135,000, determined by affinity crosslinking and SDS gel electrophoresis under reducing conditions.

Adrenal Medulla↗