Glycerol kinase deficiency: evidence for complexity in a single gene disorder.

Glycerol kinase deficiency (GKD) occurs as part of an Xp21 contiguous gene syndrome or as isolated GKD. The isolated form can be either symptomatic with episodic metabolic and central nervous system (CNS) decompensation or asymptomatic with hyperglycerolemia and glyceroluria only. To better understand the pathogenesis of isolated GKD, we sought individuals with point mutations in the GK coding region and measured their GK enzyme activities. We identified six individuals with missense mutations: four (N288D, A305V, M428T, and Q438R) among males who were asymptomatic and two (D198G, R405Q) in individuals who were symptomatic. GK activity measured in lymphoblastoid cell lines or fibroblasts was similar for the symptomatic and the asymptomatic individuals. Mapping of the individuals' missense mutations to the three-dimensional structure of Escherichia coli GK revealed that the symptomatic individuals' mutations are in the same region as a subset of the mutations among the asymptomatic individuals, adjacent to the active-site cleft. We conclude that, like many other disorders, GK genotype does not predict GKD phenotype. We hypothesize that the phenotype of an individual with GKD is a complex trait influenced by additional, independently inherited genes.

Race-related differences among patients with left ventricular dysfunction: observations from a biracial angiographic cohort. Harlem-Bassett LP(A) Investigators.

BACKGROUND: This study was designed to describe race-related differences in left ventricular function among a consecutive series of patients undergoing cardiac catheterization and to identify racial differences in coexistent medical and social conditions that are associated with the development of heart failure (HF). METHODS AND RESULTS: This was a prospective cohort study conducted at 2 university-affiliated teaching hospitals. We used the database of the Harlem-Bassett Lp(a) Study. We included all black (N = 143) or white (N = 313) patients from the main study database for whom complete survey, laboratory, coronary angiographic, and ventriculographic data were available. "Left ventricular dysfunction" was arbitrarily defined as an ejection fraction < or =0.40 or prior pharmacologic treatment for HF. We found that blacks were younger, had a higher proportion of women, and had fewer years of formal education than their white counterparts. Coronary artery disease was less common among blacks, although this group had a higher prevalence of hypertension, diabetes, cigarette smoking, illicit drug use, and alcohol consumption. Black patients had a higher prevalence of previous treatment for HF, larger left ventricular volumes, and lower ejection fractions than white patients. Blacks with left ventricular dysfunction were more likely to have had a previous myocardial infarction or a history of hypertension compared with those without left ventricular dysfunction. CONCLUSIONS: Regarding left ventricular dysfunction and HF, we conclude that blacks seem to have a much higher burden of disease than whites. Our observations support prior evidence that hypertension is linked to race-related differences in the epidemiology of HF. The interaction between race and access to quality care for HF remains an important area for future investigation.