Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused clinical hypercortisolism and Cushing's syndrome. Studies of the toxicity of Medroxyprogesterone Acetate list the commonest adverse events at 500 mg/day as weight gain, water retention, increased blood pressure, tremor, moon face, sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid-like effects are seen in up to 30% of patients treated for longer than 6 weeks with mostly large doses of the order of 1500 mg/day but Cushing's syndrome has been reported in patients taking 400 mg/day. Neither the glucocorticoid-like effects or Cushing's syndrome have been previously observed with Megestrol Acetate. In the elderly female population receiving progestogens for neoplastic disease the progestogen itself could be an appreciable cause of morbidity both by causing glucocorticoid-like effects and Cushing's syndrome but also by lack of awareness of the danger of sudden withdrawal of these compounds when the hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms could be easily overlooked unless appropriate testing for Cushing's syndrome is carried out. While the progestogen may have to be continued indefinitely a dose decrease may be feasible with reduction of morbidity.
 ...
PMID:Progestogens and Cushing's syndrome. 852 28

Neonatal-onset movement disorders, especially in combination with seizures, are rare and often related to mitochondrial disorders. 3-methylglutaconic aciduria (3-MGA-uria) is a marker for mitochondrial dysfunction. In particular, consistently elevated urinary excretion of 3-methylglutaconic acid is the hallmark of a small but growing group of inborn errors of metabolism (IEM) due to defective phospholipid remodeling or mitochondrial membrane-associated disorders (mutations in TAZ, SERAC1, OPA3, CLPB, DNAJC19, TMEM70, TIMM50). Exome/genome sequencing is a powerful tool for the diagnosis of the clinically and genetically heterogeneous mitochondrial disorders. Here, we report 11 individuals, of whom 2 are previously unpublished, with biallelic variants in high temperature requirement protein A2 (HTRA2) encoding a mitochondria-localized serine protease. All individuals presented a recognizable phenotype with neonatal- or infantile-onset neurodegeneration and death within the first month of life. Hallmark features were central hypopnea/apnea leading to respiratory insufficiency, seizures, neutropenia, 3-MGA-uria, tonus dysregulation, and dysphagia. Tremor, jitteriness, dystonia, and/or clonus were also common. HTRA2 defect should be grouped under the IEM with 3-MGA-uria as discriminating feature. Clinical characteristics overlap with other disorders of this group suggesting a common underlying pathomechanism. Urinary organic acid analysis is a noninvasive and inexpensive test that can guide further genetic testing in children with suggestive clinical findings.
 ...
PMID:HTRA2 Defect: A Recognizable Inborn Error of Metabolism with 3-Methylglutaconic Aciduria as Discriminating Feature Characterized by Neonatal Movement Disorder and Epilepsy-Report of 11 Patients. 3011 19