Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study.

AIMS: Lysosomal α-galactosidase A deficiency (Fabry disease (FD)) was considered an X-linked recessive disorder but is now viewed as a variable penetrance dominant trait. The prevalence of FD is 1 in 40 000-117 000 but the ascertainment of late-onset cases and degree of female penetrance makes this unclear. Its prevalence in the general population, especially in patients with abnormal renal function is unclear. This study attempted to identify the prevalence of FD in patients with abnormal renal function results from laboratory databases. METHODS: Electronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of reduced estimated glomerular filtration rate categorised by age on one occasion or more over a 3-year time interval. Patients were recalled and a dried blood spot sample was collected for the determination of α-galactosidase A activity by fluorimetric enzyme assay in men and mass spectrometry assays of α-galactosidase A and lyso-globotriaosylceramide (lyso-GL-3) concentrations in women. RESULTS: Samples were obtained from 1084 patients identified with reduced renal function. No cases of FD were identified in 505 men. From 579 women, one subject with reduced α-galactosidase activity (1.5 µmol/L/h) and increased Lyso-GL-3 (5.5 ng/mL) was identified and shown to be heterozygous for a likely FD pathogenic variant (GLA c.898C>T; p.L300F; Leu300Phe). It was later confirmed that she was a relative of a known affected patient. CONCLUSIONS: Pathology databases hold routine information that can be used to identify patients with inherited errors of metabolism. Biochemical screening using reduced eGFR alone has a low yield for unidentified cases of Fabry Disease.

Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study.

AIMS: Adult-onset inherited errors of metabolism can be difficult to diagnose. Some cases of potentially treatable myopathy are caused by autosomal recessive acid α-1,4 glucosidase (acid maltase) deficiency (Pompé disease). This study investigated whether screening of asymptomatic patients with elevated creatine kinase (CK) could improve detection of Pompé disease. METHODS: Pathology databases in six hospitals were used to identify patients with elevated CK results (>2× upper limit of normal). Patients were recalled for measurement of acid α-1,4 glucosidase activity in dried blood spot samples. RESULTS: Samples were obtained from 812 patients with elevated CK. Low α-glucosidase activity was found in 13 patients (1.6%). Patients with neutropaenia (n=4) or who declined further testing (n=1) were excluded. Confirmation plasma specimens were obtained from eight individuals (1%) for a white cell lysosomal enzyme panel, and three (0.4%) were confirmed to have low α-1,4-glucosidase activity. One patient was identified as a heterozygous carrier of an acid α-1,4 glucosidase c.-32-13 G>T mutation. Screening also identified one patient who was found to have undiagnosed Fabry disease and one patient with McArdle's disease. One patient later presented with Pompé's after an acute illness. Including the latent case, the frequency of cases at 0.12% was lower than the 2.5% found in studies of patients with raised CK from neurology clinics (p<0.001). CONCLUSIONS: Screening pathology databases for elevated CK may identify patients with inherited metabolic errors affecting muscle metabolism. However, the frequency of Pompé's disease identified from laboratory populations was less than that in patients referred for neurological investigation.

Randomized clinical trial comparing 2 support surfaces: results of the Prevention of Pressure Ulcers Study.

OBJECTIVE: To determine whether a viscoelastic polymer (energy absorbing) foam mattress was superior to a standard hospital mattress for pressure ulcer prevention and to analyze the cost-effectiveness in comparison with standard hospital mattresses. DESIGN: Unblinded, randomized, prospective trial. SETTING: Elderly acute care, rehabilitation, and orthopedic wards at 3 hospitals in the United Kingdom. PARTICIPANTS: 1168 patients at risk of developing pressure ulcers (Waterlow score, 15 to 20), with a median age of 83 years (25th to 75th percentile range, 79-87). INTERVENTIONS: Participants were allocated to either the experimental equipment (CONFOR-Med mattress/cushion combination) or a standard mattress/cushion combination; all were given standard nursing care. Pressure areas were observed daily. MAIN OUTCOME MEASURE: Development of nonblanching erythema. RESULTS: A significant decrease in the incidence of blanching erythema (26.3% to 19.9%; P =.004) and a nonsignificant decrease in the incidence of nonblanching erythema occurred in participants allocated to the experimental equipment. However, when the survival curve plots were analyzed at 7 days, both categories showed statistically significant decreases (P =.0015 and P =.042, respectively). Participants on standard equipment had a relative odds ratio of 1.36 (95% confidence interval [CI], 1.10-1.69) for developing blanching erythema or worse and 1.46 (95% CI, 0.90-1.82) for developing nonblanching erythema or worse. To prevent nonblanching erythema, the number needed to treat (NNT) was 41.9 (95% CI, -82.6-15.3). To prevent any erythema (blanching or nonblanching), the NNT was 11.5 (95% CI, 41.6-9.3). Participants with blanching or nonblanching erythema were significantly less mobile than participants with normal skin and more likely to have worsening mobility (P <.001). For participants with similar pressure ulcer status, mattress type was not associated with difference in mobility. CONCLUSIONS: Regardless of prevention routine, pressure ulcers occur. In this study, the experimental equipment showed statistical significance to standard equipment for prevention of blanching erythema; significance was not achieved for nonblanching erythema. Trend and survival analysis show that a larger study is required to determine whether this nonsignificant difference is genuine.