RESUMEN
Avoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e.g. genes associated with amylase production) which may explain their persistent symptoms. WES confirmed the GSD-Ia diagnosis, with all three probands harboring the homozygous p.R83C variant in G6PC. While no other significant variants were identified for patients A and B, a homozygous p.G276V variant in the SI gene was detected in patient C, establishing the dual-diagnosis of GSD-Ia and Sucrase-Isomaltase Deficiency. To conclude, we suggest that WES should be considered in GSD-Ia patients who show persistent symptoms despite optimal dietary management.
Asunto(s)
Glucosa-6-Fosfatasa , Enfermedad del Almacenamiento de Glucógeno Tipo I , Glucosa-6-Fosfatasa/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , AlmidónRESUMEN
RATIONALE: Increased levels of systemic markers of inflammation have been reported in patients with impaired lung function due to obstructive or restrictive lung disease. OBJECTIVE: We tested the hypothesis that a decline in lung function within the normal range may be associated with a systemic subclinical inflammation. METHODS: Pulmonary function tests, cardiorespiratory fitness, components of the metabolic syndrome, and high-sensitivity C-reactive protein (CRP) were determined in 1,131 subjects without known pulmonary disease. MEASUREMENTS AND MAIN RESULTS: Ninety-six of the study participants (8.5%) had FEV(1) of less than 80% of predicted values. There was a strong inverse association between CRP levels and quartiles of FEV(1). The median CRP levels in nonsmoking participants were 2.5, 1.8, 1.7, and 1.3 mg/L in the first, second, third, and forth FEV(1) quartiles, respectively (p < 0.0001). A similar inverse association was present in smoking subjects (median CRP levels were 3.8, 2.3, 2.0, and 1.9 mg/L in the first, second, third, and fourth FEV(1) quartiles, respectively; p < 0.0001). These associations remained highly significant after adjustment for age, sex, components of the metabolic syndrome, and fitness level (p = 0.0005). CONCLUSIONS: An inverse linear relationship exists between CRP concentrations and measures of pulmonary function in subjects without pulmonary disease and in never-smokers. These results indicate that systemic inflammation may be linked to early perturbations of pulmonary function.