Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myotonic dystrophy (MyD) is a multisystemic disorder characterized by muscle atrophy, myotonia and cataract. Although a number of reports have been accumulated showing the presence of bone changes in MyD patients, there are few published papers in which calcium metabolism was precisely examined. In the previous paper, we reported that intestinal calcium absorption was increased in MyD patients due to the elevation of plasma 1,25(OH)2D level. The present study was designed to elucidate the mechanism of increased level of serum 1,25(OH)2D concentration in MyD patients. Calcium tolerance tests were performed in 13 patients with MyD, 13 patients with other neuromuscular disorders (non-MyD) and 12 healthy control subjects according to the method of Broadus et al. Immunoreactive PTH (iPTH) levels and cyclic AMP (cAMP) levels were measured using commercially available RIA kits. The basal plasma calcium levels in MyD were slightly higher than those in the other two groups, but the difference was not statistically significant. The plasma 1,25(OH)2D levels, calcemic responses and calciuric responses in MyD were significantly higher than those in the other two groups. Serum iPTH levels in MyD (0.462 +/- 0.320 ng/ml, Mean +/- SD) were significantly higher than those in the other two groups (normal subjects 0.175 +/- 0.092, non-MyD 0.200 +/- 0.111; p less than 0.02). Nephrogenous cyclic AMP (NcAMP) levels in MyD (2.094 +/- 3.244 nmol/100 ml GF) were also higher than those in normal subjects (0.907 +/- 0.212, p less than 0.05) and in non-MyD (0.929 +/- 0.335, p less than 0.05). There was a significant correlation between serum iPTH levels and NcAMP levels, and therefore it might be possible to accept that these two measurements reflect the level of parathyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Abnormal calcium metabolism in myotonic dystrophy (II): Increased level of nephrogenous cyclic AMP and serum immunoreactive parathyroid hormone]. 285 65

Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by peculiar clinical features. Its molecular basis is the unstable expansion of a CTG triplet repeat in the gene encoding myotonin protein kinase (Mt-PK), the nucleotide sequence of which has extensive homology to the cyclic AMP (cAMP)-dependent protein kinase gene. Extensive efforts have been made to clarify the signal transduction pathway in which the responsible gene operates, but confirming evidence has yet to be obtained. Because some symptoms in DM are similar to those in hypoparathyroidism, we divided 24 DM patients into two groups on the basis of their serum calcium levels; Group 1, those with normocalcemia (11 patients), and group 2, those with hypocalcemia (13 patients). The highly sensitive parathyroid hormone (HS-PTH) plasma levels in group 1 were within normal limits, whereas those in group 2 were abnormally high. Laboratory findings for the group 2 patients resembled those for pseudohypoparathyroidism (PHP), whereas those for group 1 patients were normal. The Ellsworth-Howard (EH) test was used to determine which type of PHP the group 2 patients belonged to. Both the phosphaturic (delta P) and urinary cAMP (UcAMP) responses were estimated. The delta P responses in group 2 were significantly lower than those in group 1, but their UcAMP responses did not differ. This is evidence that group 2 patients had PHP type II, whereas group 1 patients were normal. We also investigated whether the disease severity differed between the groups. Cataracts, ectopic calcifications, and ossifications, which are associated with PHP, were more frequent in group 2. In addition, the mean IQ in that group was significantly lower. Clinically, the group 2 signs agreed well with those of PHP, whereas for group 1 there was only a slight similarity. These results are additional evidence that the patients in group 2 have abnormal calcium metabolism, the abnormality being in the postadenylate cyclase-cAMP pathway in the renal tubular cells. The degree of (CTG)n expansion, the so-called expanded DNA fragment (EF) size, was determined by standard Southern blot analysis. The allelic EF sizes in both groups were greater than in the healthy controls. Moreover, those in group 2 were significantly longer than those in group 1. We therefore investigated whether EF size is correlated with the serum calcium and plasma PTH levels, the delta P responses in the EH test, and IQ. All these items were significantly correlated with EF size. Our findings show that the expanded DNA fragment size in DM is correlated with the degree of abnormal calcium metabolism.
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PMID:Abnormal calcium metabolism in myotonic dystrophy as shown by the Ellsworth-Howard test and its relation to CTG triplet repeat length. 940 36

The pathogenetic mechanisms involved in the development of sporadic idiopathic hypoparathyroidism are currently under investigation. Although autoantibodies against the calcium-sensing receptor (CaSR) have been implicated to play a role, these could be demonstrated in only 49% of a group of 51 patients with sporadic idiopathic hypoparathyroidism that we previously studied. Therefore, we investigated 49 of these patients further, regardless of their antibody status, and looked for mutations in the section of the PTH gene sequence that coded for prepro-PTH as well as the 3'-untranslated region (3'-UTR) of the gene, which is believed to be involved in the stability of its mRNA. We also examined the relationship between the clinical manifestations of the disease and the occurrences of two commonly observed single nucleotide polymorphisms (SNPs) in the PTH gene. In 49 of the patients with idiopathic hypoparathyroidism and in 55 healthy controls, the SNPs were characterized by restriction analysis using DraII and BstBI enzymes. In a subset of these patients, exons 2 and 3 of the PTH gene (n = 37) and its 3'-UTR region (n = 40) were also sequenced. No mutations were observed in the segment of the PTH gene coding for the signal peptide, prohormone, or the 3'-UTR region. However, three well described SNPs were observed: 1) an A-->G substitution in intron 1 in 35.1% of the patients; 2) a G-->A substitution in intron 2, characterized by BstBI, in one or both alleles in 27%; and 3) a C-->A substitution at codon 52 (CGA) of exon 3, characterized by DraII, in one or both alleles in 59.7% of the patients. There was no significant difference in the frequency of occurrence of these SNPs between the patient and the control groups. Furthermore, the mean age at onset of symptoms, body mass index, frequency of cataract, tetany, convulsion, basal ganglia calcification, serum calcium, inorganic phosphorus, and intact PTH were not significantly different between patients with and without the above-described SNPs. Thus, the data from this report demonstrate that in patients with sporadic idiopathic hypoparathyroidism, neither the clinical manifestations nor the biochemical indexes of the disease are related to the occurrence of mutations or SNPs in the PTH gene. Because neither patient nor control samples exhibited any variations in the sequence of their 3'-UTR regions, it is unlikely that mRNA instability is a factor in the pathogenesis of the disease. Additional studies are required to investigate the role of other genes and autoantigens that may be involved in the genesis of idiopathic hypoparathyroidism.
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PMID:Parathyroid hormone gene polymorphism and sporadic idiopathic hypoparathyroidism. 1547 73

We report a 30-yr-old lady who was being treated as postpartum psychosis. Patient had generalized tonic clonic convulsions and was found to have bilateral cataract. Her serum calcium, serum magnesium and serum parathyroid were low. On correction of serum magnesium her PTH did not increase. She was hence diagnosed as primary hypoparathyroidism. On correction of her serum calcium her psychosis improved.
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PMID:Primary hypoparathyroidism: psychosis in postpartum period. 2118 1

Nonsurgical hypoparathyroidism (HypoPT) is a rare disorder most often caused by mutations in different genes. It is characterized by hypocalcaemia with inappropriately low PTH levels. Knowledge about this group of patients, including their mortality and morbidity, is very sparse. The aim was to identify all patients diagnosed with nonsurgical HypoPT in Denmark and assess their mortality and risk of complications. Through registers and review of individual patient hospital charts we identified all patients diagnosed with nonsurgical HypoPT in Denmark between 1977 and 2012. We assessed their mortality and morbidity by comparing them with a group of age- and gender-matched population-based controls. We identified a total of 180 patients with nonsurgical HypoPT among whom 123 (68%) were alive at the date of follow-up (prevalence of 2.3/100,000 inhabitants). Compared with controls, mortality was not increased, but patients had a significantly increased risk of renal insufficiency (hazard ratio [HR] 6.01), cardiovascular diseases (HR 1.91), neuropsychiatric complications (HR 2.45), infections (HR 1.94), seizures (HR 10.05), cataract (HR 4.21), and fractures at the upper extremities (HR 1.93). In contrast patients had significantly reduced risk of malignant diseases (HR 0.44). In conclusion, nonsurgical HypoPT is a rare disease associated with a number of complications that should be considered when taking care of these patients.
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PMID:The Epidemiology of Nonsurgical Hypoparathyroidism in Denmark: A Nationwide Case Finding Study. 2575 91