Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B(1) deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals.
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PMID:Neurodegenerative disorders associated with diabetes mellitus. 1517 61

At onset mitochondrial disorders (MID) frequently manifest as a mono-organic problem but turn into multisystem disease during the disease course in most of the cases. Organs/tissues most frequently affected in MID are the cerebrum, peripheral nerves, and the skeletal muscle. Additionally, most of the inner organs may be affected alone or in combination. Hematological manifestations of MID include aplastic, megaloblastic, or sideroblastic anemia, leukopenia, neutropenia, thrombocytopenia, or pancytopenia. In single cases either permanent or recurrent eosinophilia has been observed. Hematological abnormalities may occur together with syndromic or nonsyndromic MIDs. Syndromic MIDs, in which hematological manifestations predominate, are the Pearson syndrome (pancytopenia), Kearns-Sayre syndrome (anemia), Barth syndrome (neutropenia), and the autosomal recessive mitochondrial myopathy, lactic acidosis and sideroblastic anemia syndrome. In single cases with Leigh's syndrome, MERRF (myoclonic epilepsy and ragged-red fiber) syndrome, Leber's hereditary optic neuropathy, and Friedreich's ataxia anemia has been described. Anemia, leukopenia, thrombocytopenia, eosinophilia, or pancytopenia can frequently also be found in nonsyndromic MIDs with or without involvement of other tissues. Therapy of blood cell involvement in MID comprises application of antioxidants, vitamins, iron, bone marrow-stimulating factors, or substitution of cells.
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PMID:Hematological manifestations of primary mitochondrial disorders. 1763 11

The catalytic properties of many enzymes depend on the participation of vitamins as obligatory cofactors. Vitamin B12 (cobalamin) and folic acid (folate) deficiencies in infants and children classically present with megaloblastic anemia and are often accompanied by neurological signs. A number of rare inborn errors of cobalamin and folate absorption, transport, cellular uptake, and intracellular metabolism have been delineated and identification of disease-causing mutations has improved our ability to diagnose and treat many of these conditions. Two inherited defects in biotin metabolism are known, holocarboxylase synthetase and biotinidase deficiency. Both lead to multiple carboxylase deficiency manifesting with metabolic acidosis, neurological abnormalities, and skin rash. Thiamine-responsive megaloblastic anemia is characterized by megaloblastic anemia, non-type I diabetes, and sensorineural deafness that responds to pharmacological doses of thiamine (vitamin B1). Individuals affected with inherited vitamin E deficiencies including ataxia with isolated vitamin E deficiency and abetalipoproteinemia present with a spinocerebellar syndrome similar to patients with Friedreich's ataxia. If started early, treatment of these defects by oral or parenteral administration of the relevant vitamin often results in correction of the metabolic defect and reversal of the signs of disease, stressing the importance of early and correct diagnosis in these treatable conditions.
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PMID:Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E. 2362 2