Uncovering genetic causes of hypophosphatemia.

BACKGROUND: Chronic hypophosphatemia can result from a variety of acquired disorders, such as malnutrition, intestinal malabsorption, hyperparathyroidism, vitamin D deficiency, excess alcohol intake, some drugs, or organ transplantation. Genetic disorders can be a cause of persistent hypophosphatemia, although they are less recognized. We aimed to better understand the prevalence of genetic hypophosphatemia in the population. METHODS: By combining retrospective and prospective strategies, we searched the laboratory database of 815,828 phosphorus analyses and included patients 17-55 years old with low serum phosphorus. We reviewed the charts of 1287 outpatients with at least 1 phosphorus result ≤2.2 mg/dL. After ruling out clear secondary causes, 109 patients underwent further clinical and analytical studies. Among them, we confirmed hypophosphatemia in 39 patients. After excluding other evident secondary causes, such as primary hyperparathyroidism and vitamin D deficiency, we performed a molecular analysis in 42 patients by sequencing the exonic and flanking intronic regions of a panel of genes related to rickets or hypophosphatemia (CLCN5, CYP27B1, dentin matrix acidic phosphoprotein 1, ENPP1, FAM20C, FGFR1, FGF23, GNAS, PHEX, SLC34A3, and VDR). RESULTS: We identified 14 index patients with hypophosphatemia and variants in genes related to phosphate metabolism. The phenotype of most patients was mild, but two patients with X-linked hypophosphatemia (XLH) due to novel PHEX mutations had marked skeletal abnormalities. CONCLUSION: Genetic causes should be considered in children, but also in adult patients with hypophosphatemia of unknown origin. Our data are consistent with the conception that XLH is the most common cause of genetic hypophosphatemia with an overt musculoskeletal phenotype.

Mild Hypophosphatemia-Associated Conditions in Children: The Need for a Comprehensive Approach.

To better understand the causes of hypophosphatemia in children, we evaluated all serum phosphate tests performed in a tertiary hospital with unexpected but persistent temporary or isolated hypophosphatemia over an 18 year period. We collected 29,279 phosphate tests from 21,398 patients, of which 268 (1.2%) had at least one result showing hypophosphatemia. We found that endocrinopathies (n = 60), tumors (n = 10), and vitamin D deficiency (n = 3) were the medical conditions most commonly associated with mild hypophosphatemia, but in many patients the cause was unclear. Among patients with endocrinopathies, those with diabetes mellitus were found to have lower mean serum phosphate levels (mean 3.4 mg/dL) than those with short stature (3.7 mg/dL) or thyroid disorders (3.7 mg/dL). In addition, we found a correlation between glycemia and phosphatemia in patients with diabetes. However, despite the potential relevance of monitoring phosphate homeostasis and the underlying etiologic mechanisms, renal phosphate losses were estimated in less than 5% of patients with hypophosphatemia. In the pediatric age group, malignancies, hypovitaminosis D, and endocrine disorders, mostly diabetes, were the most common causes of hypophosphatemia. This real-world study also shows that hypophosphatemia is frequently neglected and inadequately evaluated by pediatricians, which emphasizes the need for more education and awareness about this condition to prevent its potentially deleterious consequences.

Altered blood glucose concentration is associated with risk of death among patients with community-acquired Gram-negative rod bacteremia.

BACKGROUND: Altered blood glucose concentration is commonly observed in patients with sepsis, even among those without hypoglycemic treatments or history of diabetes mellitus. These alterations in blood glucose are potentially detrimental, although the precise relationship with outcome in patients with bacteremia has not been yet determined. METHODS: A retrospective cohort study design for analyzing patients with Gram negative rod bacteremia was employed, with the main outcome measure being in-hospital mortality. Patients were stratified in quintiles accordingly deviation of the blood glucose concentration from a central value with lowest mortality. Cox proportional-hazards regression model was used for determining the relationship of same day of bacteremia blood glucose and death. RESULTS: Of 869 patients identified 63 (7.4%) died. Same day of bacteremia blood glucose concentration had a U-shaped relationship with in-hospital mortality. The lowest mortality (2%) was detected in the range of blood glucose concentration from 150 to 160 mg/dL. Greater deviation of blood glucose concentration from the central value of this range (155 mg/dL, reference value) was directly associated with higher risk of death (p = 0.002, chi for trend). The low-risk group (quintile 1) had a mortality of 3.3%, intermediate-risk group (quintiles 2, 3 and 4) a mortality of 7.1%, and the high-risk group (quintile 5) a mortality of 12.05%. In a multivariable Cox regression model, the hazard ratio for death among patients in the intermediate-risk group as compared with that in the low risk group was 2.88 (95% confidence interval, 1.01 to 8.18; P = 0.048), and for the high risk group it was 4.26 (95% confidence interval, 1.41 to 12.94; P = 0.01). CONCLUSIONS: Same day of bacteremia blood glucose concentration is related with outcome of patients with Gram-negative rod bacteremia. Lowest mortality is detected in patients with blood glucose concentration in an interval of 150-160 mg/dL. Deviations from these values are associated with an increased risk of death.

Diabetes does not affect outcome in patients with Enterobacteriaceae bacteremia.

BACKGROUND: There is limited information about the effect of diabetes on the prognosis of patients with bacterial infections. We performed a retrospective cohort study to investigate possible correlations between diabetes and prognosis in patients with Enterobacteriaceae bacteremia. METHODS: We reviewed the medical charts of 1112 patients who were treated at a community teaching hospital for Enterobacteriaceae bacteremia from January 1997 through June 2007. Factors associated with in-hospital mortality were analyzed by logistic regression analysis. RESULTS: Among the 1112 patients with Enterobacteriaceae bacteremia, 181 (16.3%) were diabetic patients; 90 patients (8.1%) died while in the hospital. Compared to non-diabetic patients, diabetic patients were older (75.4 +/- 11.9 years vs. 70 +/- 16.6 years, p < 0.001) and had more comorbidities. However, mortality among diabetic and non-diabetic patients was not different [7.2% vs. 8.2%, RR 1.13; 95% CI (0.67-1.9); p = 0.39]. In a multivariate analysis, the variables associated with in-hospital mortality were age, the origin of the bacteremia, and the presence of immunosuppression. Diabetes was not associated with outcome. CONCLUSION: In this cohort of patients with Enterobacteriaceae bacteremia, diabetes was not associated with a poorer prognosis.