Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 71-year-old white man developed direct antiglobulin positive haemolytic anaemia after 16 months of levodopa therapy for Parkinson's disease. Immunoglobulin G autoantibodies directed against Rh antigens were found in the patient's serum and on his erythrocytes. Reduction of levodopa dosage to one sixth with the aid of a peripheral decarboxylase inhibitor (benserazide) largely eliminated autoimmune haemolysis while maintaining adequate control of neurologic symptoms.
 ...
PMID:Dose-related levodopa-induced haemolytic anaemia. 40 77

The fact that levodopa, a drug used for the treatment of Parkinson's disease induces a direct Coombs-positive reaction in about 15% of treated patients, indicating the presence of auto-antibodies against the patient's red blood cells (RBCs), is well known. Another known fact is that only 1% of those patients do actually develop auto-immune haemolytic anaemia. In this paper, we describe our findings utilizing the direct ELISA, a method for measuring the presence of IgM and IgG auto-antibodies on the patients' red blood cells (RBCs), as well as an indirect ELISA, testing the presence of antibodies in their serum. The tests were performed on 8 patients, 7 of whom had been receiving the drug for long periods of time. Our results show that the serum antibodies precede the bound antibodies in a significant fashion and that the severity of the anaemia is directly related to the amount of auto-antibodies. Since auto-antibodies do not seem to be directed against the drug itself, some modification of the RBC must occur. For this reason, we attempted to determine whether patients receiving the drug show any morphological changes of their RBCs which could be determined by scanning electron microscopy (SEM) and whether these changes could be related to direct and indirect ELISA. In most levodopa-treated patients, a small number of echinocytes could be observed by SEM, while in 1 patient who suffered a severe anaemic phase, a very high percentage of the RBCs were echinocytes and spherocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Electron microscopy of red blood cells altered by auto-immunity-inducing drugs. 239 95

A 25-year-old man with exertional myoglobinuria had no evidence of hemolytic anemia, but he had severe parkinsonism that was responsive to levodopa. Phosphoglycerate kinase (PGK) activity was markedly decreased in muscle, and molecular analysis of the PGK1 gene identified the p.T378P mutation that was recently reported in a patient with isolated myopathy. This case reinforces the concept that PGK deficiency is a clinically heterogeneous disorder and raises the question of a relationship between PGK deficiency and idiopathic juvenile Parkinson disease.
 ...
PMID:Myopathy and parkinsonism in phosphoglycerate kinase deficiency. 2015 63

Phosphoglycerate kinase 1 (PGK-1) is a glycolytic enzyme encoded by PGK-1, which maps to the X chromosome. PGK-1 deficiency causes X-linked recessive hereditary chronic hemolytic anemia, myopathy, and neurological disorders due to insufficient ATP regeneration. Early-onset parkinsonism has occasionally been reported as a neurological complication of this condition. However, heterozygous carriers of PGK-1 deficiency were thought to be neurologically asymptomatic. Here, we report a boy with PGK-1 deficiency and his mother, a carrier of a heterozygous mutation in PGK-1, both of whom presented with early-onset parkinsonism. The boy developed parkinsonism at 9 years of age. His parkinsonism partially responded to levodopa treatment. 123l-metaiodobenzylguanidine (MIBG) uptake was normal. His mother, who exhibited normal PGK-1 activity in erythrocytes, developed parkinsonism at 36 years of age. Her symptoms were undistinguishable from those of Parkinson's disease (PD), despite her normal uptake of MIBG. Neither a point mutation in nor multiplication of SNCA was found. Additionally, hotspots of LRRK2 and GBA were not mutated. To our knowledge, this report provides the first description of parkinsonism in a carrier of PGK-1 deficiency. Interestingly, PGK-1 is located within the confirmed susceptibility locus for PD known as PARK12. These observations suggest that PGK-1 mutations confer susceptibility to PD.
 ...
PMID:Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism? 2864 13