Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032290 (aspiration pneumonia)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 10-wk-old infant girl with severe hypertrophy of the septal and atrial walls by cardiac ultrasound, developed progressive ventricular wall thickening and died of aspiration pneumonia at 5 mo of age. Postmortem examination revealed ventricular hypertrophy and massive atrial wall thickening due to glycogen accumulation. A skeletal muscle biopsy showed increased free glycogen and decreased activity of phosphorylase b kinase (PHK). The report of a pathogenic mutation (R531Q) in the gene (PRKAG2) encoding the gamma2 subunit of AMP-activated protein kinase (AMPK) in three infants with congenital hypertrophic cardiomyopathy, glycogen storage, and "pseudo PHK deficiency" prompted us to screen this gene in our patient. We found a novel (R384T) heterozygous mutation in PRKAG2, affecting an arginine residue in the N-terminal AMP-binding domain. Like R531Q, this mutation reduces the binding of AMP and ATP to the isolated nucleotide-binding domains, and prevents activation of the heterotrimer by metabolic stress in intact cells. The mutation was not found in DNA from the patient's father, the only available parent, and is likely to have arisen de novo. Our studies confirm that mutations in PRKAG2 can cause fatal infantile cardiomyopathy, often associated with apparent PHK deficiency.
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PMID:Fatal infantile cardiac glycogenosis with phosphorylase kinase deficiency and a mutation in the gamma2-subunit of AMP-activated protein kinase. 1766 62

Activating mutations in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium (KATP) channel is a cause of neonatal diabetes associated with various neurological disorders that include developmental delay, epilepsy, and neonatal diabetes (known together as DEND syndrome). This article reports a girl who developed infantile spasms and early onset diabetes mellitus at the age of 3 months and revealed DEND syndrome with a heterozygous activating mutation in Kir6.2. Infantile spasms with hypsarrhythmia on the electroencephalogram were severe and refractory to steroids. Steroids combined with oral sulfonylurea, a drug that closes the ATP-sensitive potassium channel by an independent mechanism, allowed partial and transitory control of the epilepsy. However, the child still exhibited severe encephalopathy and died of aspiration pneumonia. The role of oral sulfonylurea as an anticonvulsant in DEND syndrome associated with Kir6.2 mutation is discussed.
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PMID:Infantile spasms as an epileptic feature of DEND syndrome associated with an activating mutation in the potassium adenosine triphosphate (ATP) channel, Kir6.2. 1789 Apr 19