Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune gastrointestinal dysmotility (AGID) can result from paraneoplastic onconeuronal antibodies. Patients may present with regional hypomotility anywhere along the gastrointestinal tract. We report a case of a woman who developed an insidious sensory neuropathy and achalasia. She was found to have a high-titer of N-type voltage gated-calcium channel (VGCC) antibodies. She demonstrated clinical and electrophysiological improvement of her neuropathy, as well as improvement of her swallowing and gait, after treatment with intravenous immunoglobulins.
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PMID:Achalasia, chronic sensory neuropathy, and N-type calcium channel autoantibodies: beneficial response to IVIG. 2618 99

POLG gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA (mtDNA) replication and repair. Mutations in POLG have been linked to a spectrum of clinical phenotypes, resulting in autosomal recessive or dominant mitochondrial diseases. These mutations have been associated with heterogeneous phenotypes, presenting with varying severity and at different ages of onset, ranging from the neonatal period to late adult life. We screened 13 patients for POLG mutations. All patients underwent a complete neurological examination, and in most of cases, muscle biopsy was performed. We detected 15 different variations in 13 unrelated Italian patients. Two mutations were novel and mapped in the pol domain (p.Thr989dup and p.Ala847Thr) of the enzyme. We also report new cases carrying controversial variations previously described as incompletely penetrant or a variant of unknown significance. Our study increases the range of clinical presentations associated with mutations in POLG gene, underlining some peculiar clinical features, such as PEO associated with corneal edema, and epilepsy, severe neuropathy with achalasia. The addition of two new substitutions, including the second report of an in-frame duplication, to the growing list of defects increases the value of POLG genetic diagnosis in a range of neurological presentations.
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PMID:Novel POLG mutations and variable clinical phenotypes in 13 Italian patients. 2813 Jun 5

Hereditary adrenocorticotropin (ACTH) resistance syndromes encompass the genetically heterogeneous isolated or Familial Glucocorticoid Deficiency (FGD) and the distinct clinical entity known as Triple A syndrome. The molecular basis of adrenal resistance to ACTH includes defects in ligand binding, MC2R/MRAP receptor trafficking, cellular redox balance, cholesterol synthesis and sphingolipid metabolism. Biochemically, this manifests as ACTH excess in the setting of hypocortisolaemia. Triple A syndrome is an inherited condition involving a tetrad of adrenal insufficiency, achalasia, alacrima and neuropathy. FGD is an autosomal recessive condition characterized by the presence of isolated glucocorticoid deficiency, classically in the setting of preserved mineralocorticoid secretion. Primarily there are three established subtypes of the disease: FGD 1, FGD2 and FGD3 corresponding to mutations in the Melanocortin 2 receptor MC2R (25%), Melanocortin 2 receptor accessory protein MRAP (20%), and Steroidogenic acute regulatory protein STAR (5-10%) respectively. Together, mutations in these 3 genes account for approximately half of cases. Whole exome sequencing in patients negative for MC2R, MRAP and STAR mutations, identified mutations in minichromosome maintenance 4 MCM4, nicotinamide nucleotide transhydrogenase NNT, thioredoxin reductase 2 TXNRD2, cytochrome p450scc CYP11A1, and sphingosine 1-phosphate lyase SGPL1 accounting for a further 10% of FGD. These novel genes have linked replicative and oxidative stress and altered redox potential as a mechanism of adrenocortical damage. However, a genetic diagnosis is still unclear in about 40% of cases. We describe here an updated list of FGD genes and provide a description of relevant mouse models that, despite some being flawed, have been precious allies in the understanding of FGD pathobiology.
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PMID:Isolated glucocorticoid deficiency: Genetic causes and animal models. 3081 90


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