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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A family had three siblings affected with classic Friedreich's ataxia. One sibling died at age 20 with fulminant diabetic ketoacidosis. The other two affected siblings are identical twin sisters without clinical diabetes but with an abnormality in the metabolism of exogenously administered glucose. These twins also have abnormal hypothalamic-pituitary control of prolactin and possibly of growth-hormone secretion. This study extends the previous reports of endocrine deficienceis associated with Friedreich's ataxia. The mechanisms underlying this association are undetermined but could represent pleiotropic effects of the Friedreich's ataxia gene or secondary manifestations of the primary central nervous system degeneration, or both.
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PMID:Abnormal function of endocrine pancreas and anterior pituitary in Friedreich's ataxia. Studies in a family. 34 4

Detailed in vivo and in vitro studies of glucose and insulin metabolism in Friedreich's ataxia patients and unaffected family members have further defined the extent of the abnormalities in carbohydrate metabolism. The high incidence of glucose intolerance and a hyperinsulinemic response to a glucose challenge in a high percentage of Friedreich's ataxia patients has been confirmed. An increased incidence of glucose intolerance among heterozygotes is suggested, while the siblings show a more normal distribution of diabetes and a nearly normal insulin response to the glucose tolerance test. Human growth hormone patterns are normal for all groups. Preliminary studies of insulin binding to erythrocytes suggest a difference in the binding characteristics among diabetic Friedreich's ataxia patients, while the binding in the non-diabetic Friedreich's ataxia group is similar to that of non-diabetic controls. Results from a small group of non-diabetic siblings suggest a normal insulin binding, while a tendency toward increased binding at low insulin concentrations among diabetic family members is noted.
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PMID:Glucose tolerance and erythrocyte insulin receptors in Friedreich's ataxia. 48 16

Glutamic and aspartic acid uptake was measured in skin fibroblasts from patients with Friedreich's Ataxia, dicarboxylic aminoaciduria, and normal individuals. The results showed no difference in uptake kinetics of either dicarboxylic amino acids between Friedreich's Ataxia and normal cells, but reduced uptake velocities in dicarboxylic aminoaciduria fibroblasts. Friedreich's Ataxia fibroblasts were, however, less calcium-dependent and more magnesium and phosphate-dependent than controls in glucose-free incubation mixture. This difference might be related to some degree of glucose intolerance by Friedreich's Ataxia fibroblasts in culture.
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PMID:Dicarboxylic amino acid uptake in normal, Friedreich's ataxia, and dicarboxylic aminoaciduria fibroblasts. 48 20

Our prospective survey of 50 ataxic patients confirms the previous finding of frequent clinical or chemical diabetes in Friedreich's ataxia. Eighteen percent of our typical cases have clinical diabetes and 40% at least an abnormal glucose tolerance curve. However, this finding does not appear to be specific to that form of ataxia. Furthermore, we have shown that most patients with ataxia have normal or low fasting insulin levels, but a hyperinsulinic response to a glucose load.
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PMID:Glucose and insulin metabolism in Friedreich's ataxia. 100 Apr 22

Friedreich's ataxia patients show evidence of an abnormally elevated and prolonged response of pyruvate and lactate to a glucose load, with normal fasting levels. However, ther is a bimodal distribution of this response with high and low pyruvate responders. This trait appears to be determined genetically, However, although in vivo tests suggest low oxidation of pyruvate, we were unable to confirm any in vitro impairment of each of the components of the pyruvate dehydrogenase (PDH) complex. We conclude that the defect is in the metabolic regulation of PDH, probably at the E3 (lipoamide dehydrogenase) step.
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PMID:Pyruvate metabolism in Friedreich's ataxia. 100 Apr 25

Multiple and different genetic defects may be associated with the development of diabetes mellitus. Friedreich's ataxia (FA) is an autosomal recessively inherited neurologic disease associated with a high prevalence of diabetes. We previously demonstrated that patients with FA have insulin resistance prior to the development of overt diabetes mellitus. To determine if insulin resistance is an inherited characteristic in this group, we performed oral glucose tolerance tests (OGTT) on first-degree relatives, 21 parents and 17 siblings, of patients with FA. While fasting concentrations were normal, both glucose and insulin concentrations in response to oral glucose were significantly elevated compared with controls. Corrected insulin responses, CIR = I x 100/G (G-70) (I = insulin, G = glucose), were not different from controls, whereas peripheral insulin activities, A = 10(4)/Ip Gp (p = values of I and G at peak glucose concentration), were significantly decreased (FA, 0.66 +/- 0.11, P less than .001; parents, 0.63 +/- 0.06, P less than .001; siblings, 0.72 +/- 0.09, P less than .01; v controls, 1.52 +/- 0.19), indicating the presence of insulin resistance in patients and first-degree relatives. Multiple discriminant analysis was used to separate patients with FA from controls. The combination of GLUT (sum of glucose values 0 to 3 hours of the OGTT) and CIR achieved significant separation (P less than .0004). Subsequent assignment of the relatives showed that 17 of 18 parents and 11 of 16 siblings (69%) fell in the range of FA, rather than with controls. These data suggest that insulin resistance is an inherited trait in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose intolerance in first-degree relatives of patients with Friedreich's ataxia is associated with insulin resistance: evidence for a closely linked inherited trait. 186 28

Local cerebral metabolic rate for glucose was studied with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 22 patients with Friedreich's ataxia and 23 age-matched normal control subjects. The diagnosis of Friedreich's ataxia was established by the history and physical findings and by excluding other diseases through laboratory investigations. PET studies revealed a statistically significant widespread increase of local cerebral metabolic rate for glucose in the brains of patients with Friedreich's ataxia who were still ambulatory, in comparison with normal control subjects. Nonambulatory patients with Friedreich's ataxia, in comparison with normal control subjects, had significantly increased local cerebral metabolic rates for glucose in the caudate and lenticular nuclei, but not in the other structures studied. The rate was significantly greater in ambulatory patients with Friedreich's ataxia than in nonambulatory patients in all structures studied except the caudate and lenticular nuclei. The data suggest that early in the course of Friedreich's ataxia, the local cerebral metabolic rate for glucose is increased extensively in the central nervous system, and as the disease progresses, it decreases in a regionally specific manner.
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PMID:Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography. 228 62

Friedreich's ataxia is known to be associated with diabetes mellitus in up to 20% of the patients. However, type, development and course of diabetes mellitus are not well characterised. We report on 3 patients (2 female and 1 male, age 13-20 years) with the combination of Friedreich's ataxia and diabetes mellitus. Diabetes mellitus was characterised as follows: (1) it was strictly insulin-dependent and ketosis-prone, (2) the average insulin requirement was 1 U/kg body weight, (3) the HLA haplotype was not typical of Type 1 (insulin-dependent) diabetes mellitus, (4) there were no positive immune parameters typical of Type 1 diabetes at the clinical onset of diabetes mellitus and (5) there was no remission. To evaluate a preclinical phase as in common autoimmune Type 1 diabetes, i.v. glucose tolerance tests (0.5 g glucose/kg body weight) were performed in 8 patients with Friedreich's ataxia without diabetes mellitus. Seven patients had normal early phase insulin response. In contrast, the glucose disappearance rate was slow in 4 and normal in 3 patients. One of the 8 patients showed a prediabetic metabolic state: the early-phase insulin response was abolished and the glucose disappearance rate was abnormal. The results suggest that diabetes in Friedreich's ataxia is caused by a loss of islet cells similar to common Type 1 diabetes but without HLA-association and without serologic evidence for autoimmune destruction of the islet cells.
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PMID:Preclinical and manifest diabetes mellitus in young patients with Friedreich's ataxia: no evidence of immune process behind the islet cell destruction. 266 85

We have characterized the abnormalities of glucose metabolism associated with Friedreich's ataxia (FA) by studying plasma glucose, insulin, growth hormone (GH), and glucagon before and after an oral glucose tolerance test (OGTT), an IV glucose load, and an IV arginine load, in 21 patients and in controls. Twelve patients were normotolerant (NT) to glucose, five glucose-intolerant (IT), and four diabetic (DM). Insulin secretion of IT patients was increased and delayed during OGTT. Interestingly, the insulin release during arginine load was significantly decreased in NT and IT as well as in DM patients. The GH response to OGTT was altered in IT patients. Plasma glucagon after an arginine load was significantly higher in patients than in controls. The results indicate that FA is associated with insulin resistance, beta-cell deficiency, and type I diabetes. These alterations might be genetically linked or metabolically related to the primary defect in FA. Their interplay or independent effects are responsible for abnormalities of glucose metabolism in FA.
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PMID:Glucose metabolism alterations in Friedreich's ataxia. 304 13

Thirty-three children presenting with "primitive" cardiomyopathy observed from January 1984 to December 1985 underwent a protocol of investigations consisting of histo-enzymatic study of the deltoid muscle, metabolic studies (glucose, free fatty acids, lactate, pyruvate, 3-hydroxybutyrate, aceto-acetate, carnitine, amino-acids blood levels after a 15 hour-fast; urinary organic acids chromatography) and a study of the fatty acids oxidation in cultured fibroblasts. In all children cardiac involvement was predominant and had been the cause for hospitalization. Cardiomyopathies of the hypertrophic type have an early onset, most often are part of a complex picture of extra-cardiac involvement and frequently have a lethal evolution. On the contrary, hypokinetic dilated cardiomyopathies are most often isolated, have a later onset and a less severe course. In 2 cases, an early hypokinetic dilated cardiomyopathy evolved toward hypertrophy. Peripheral muscular involvement is very frequent (lipidosis, mitochondrial aggregates or specific aspects) (60% of cases) in dilated as well as hypertrophic types. A precise etiological diagnosis or a strong presumption was possible in 12 of 33 cases: 2 with hereditary deficiency of the fatty acids beta-oxidation, 1 carnitine systemic deficiency, 1 Friedreich ataxia, 1 central core disease, 1 coxsackie B1 myocarditis, 6 strong suspicions of respiratory chain deficiency.
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PMID:[Apparently idiopathic primary myocardiopathies in children. The role of metabolic etiology]. 344 58


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