Investigation of muscle bioenergetics in the Marfan syndrome indicates reduced metabolic efficiency.

Background: The Marfan syndrome is an inherited multisystem disorder caused by mutations in fibrillin 1, with cardiovascular involvement being the most important feature of the phenoptype. Affected individuals have impaired flow-mediated dilatation (FMD) of large arteries of a similar severity to patients with chronic heart failure (CHF).

Aims: Skeletal muscle bioenergetics were studied in patients with the Marfan syndrome in order to evaluate the impact of impaired flow-mediated dilatation on skeletal muscle metabolism.

Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency.

We generated a knockout mouse model for guanidinoacetate N-methyltransferase (GAMT) deficiency (MIM 601240), the first discovered human creatine deficiency syndrome, by gene targeting in embryonic stem cells. Disruption of the open reading frame of the murine GAMT gene in the first exon resulted in the elimination of 210 of the 237 amino acids present in mGAMT. The creation of an mGAMT null allele was verified at the genetic, RNA and protein levels.

Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy.

Objectives: We investigated cardiac energetics in subjects with mutations in three different familial hypertrophic cardiomyopathy (HCM) disease genes, some of whom were nonpenetrant carriers without hypertrophy, using phosphorus-31 magnetic resonance spectroscopy.

Background: Familial hypertrophic cardiomyopathy is caused by mutations in sarcomeric protein genes. The mechanism by which these mutant proteins cause disease is uncertain.