RESUMEN
BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterised by renal salt wasting with hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria. It is caused by mutations in SLC12A3 encoding the sodium-chloride cotransporter on the apical membrane of the distal convoluted tubule. We report a South African family with five affected individuals presenting with hypokalaemia and unusual food cravings. METHODS: The affected individuals and two unaffected first degree relatives were enrolled into the study. Phenotypes were evaluated through history, physical examination and biochemical analysis of blood and urine. Mutation screening was performed by sequencing of SLC12A3, and determining the allele frequencies of the sequence variants found in this family in 117 ethnically matched controls. RESULTS: The index patient, her sister, father and two aunts had a history of severe salt cravings, fatigue and tetanic episodes, leading to consumption of large quantities of salt and vinegar. All affected individuals demonstrated hypokalaemia with renal potassium wasting. Genetic analysis revealed that the pseudo-dominant pattern of inheritance was due to compound heterozygosity with two novel mutations: a S546G substitution in exon 13, and insertion of AGCCCC at c.1930 in exon 16. These variants were present in the five affected individuals, but only one variant each in the unaffected family members. Neither variant was found in any of the controls. CONCLUSIONS: The diagnosis of GS was established in five members of a South African family through clinical assessment, biochemical analysis and mutation screening of the SLC12A3 gene, which identified two novel putative pathogenic mutations.
Asunto(s)
Ansia , Síndrome de Gitelman/diagnóstico , Hipopotasemia/etiología , Adulto , Anciano , Alcalosis/etiología , Calcio/orina , Familia , Femenino , Pruebas Genéticas , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/genética , Síndrome de Gitelman/fisiopatología , Haplotipos , Heterocigoto , Humanos , Magnesio/sangre , Masculino , Mutación , Linaje , Fenotipo , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , Sudáfrica , Desequilibrio Hidroelectrolítico/sangre , Desequilibrio Hidroelectrolítico/etiologíaRESUMEN
BACKGROUND: Many clinical laboratories require that specimens for serum and urine osmolality determination be processed within 3 h of sampling or need to arrive at the laboratory on ice. This protocol is based on the World Health Organization report on sample storage and stability, but the recommendation lacks good supporting data. We studied the effect of storage temperature and time on osmolality measurements. METHODS: Blood and urine samples were obtained from 16 patients and 25 healthy volunteers. Baseline serum, plasma and urine osmolality measurements were performed within 30 min. Measurements were then made at 3, 6, 12, 24 and 36 h on samples stored at 4-8â and room temperature. We compared baseline values with subsequent measurements and used difference plots to illustrate changes in osmolality. RESULTS: At 4-8â, serum and plasma osmolality were stable for up to 36 h. At room temperature, serum and plasma osmolality were very stable for up to 12 h. At 24 and 36 h, changes from baseline osmolality were statistically significant and exceeded the total allowable error of 1.5% but not the reference change value of 4.1%. Urine osmolality was extremely stable at room temperature with a mean change of less than 1 mosmol/kg at 36 h. CONCLUSIONS: Serum and plasma samples can be stored at room temperature for up to 36 h before measuring osmolality. Cooling samples to 4-8â may be useful when delays in measurement beyond 12 h are anticipated. Urine osmolality is extremely stable for up to 36 h at room temperature.
Asunto(s)
Análisis Químico de la Sangre/métodos , Urinálisis/métodos , Estudios de Casos y Controles , Humanos , Hiperglucemia/sangre , Hiperglucemia/orina , Hiponatremia/sangre , Hiponatremia/orina , Concentración Osmolar , Insuficiencia Renal/sangre , Insuficiencia Renal/orina , Manejo de Especímenes , TemperaturaRESUMEN
AIM: Serum free light chain measurements are used to follow-up and manage patients with monoclonal gammopathies, and abnormal ratios are associated with risk of progression in certain diseases. B cell dysfunction is well described in HIV and patients are at risk of developing B cell lymphomas. This study investigated whether HIV is associated with abnormal free light chain levels and the impact of antiretroviral treatment (ART) on these. METHODS: κ And λ free light chain concentrations and ratios, serum albumin and immunoglobulin G (IgG) were measured in 366 HIV positive subjects and correlated with CD4+ counts, viral loads, IgG, albumin and ART use. RESULTS: 66% were women and most were black Africans (66%), 26% were of mixed ethnicity and 8% were Caucasian or of unknown or other race. 89% were on ART. κ Free light chain values ranged from 5.59 to 357.0 mg/L (median 19.6 mg/L) and λ free light chain values ranged from 9.28 to 286 mg/L (median 22.3 mg/L). Both correlated positively with viral load and IgG and negatively with CD4+ counts and albumin concentrations. The ratio only correlated with IgG concentrations. Patients on ART had significantly lower free light chain concentrations, but the ratio was not significantly affected. CONCLUSIONS: This study demonstrated that free light chain concentrations were significantly correlated with markers of HIV disease severity, suggesting ongoing B cell dysfunction despite ART use. Free light chain ratio was not significantly affected.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Adolescente , Adulto , Anciano , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Linfocitos B/virología , Biomarcadores/sangre , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Albúmina Sérica/análisis , Albúmina Sérica Humana , Índice de Severidad de la Enfermedad , Sudáfrica , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Hyperkalemia is a common medical emergency that may result in serious cardiac arrhythmias. Standard therapy with insulin plus glucose reliably lowers the serum potassium concentration ([K(+)]) but carries the risk of hypoglycemia. This study examined whether an intravenous glucose-only bolus lowers serum [K(+)] in stable, nondiabetic, hyperkalemic patients and compared this intervention with insulin-plus-glucose therapy. METHODS: A randomized, crossover study was conducted in 10 chronic hemodialysis patients who were prone to hyperkalemia. Administration of 10 units of insulin with 100 ml of 50% glucose (50 g) was compared with the administration of 100 ml of 50% glucose only. Serum [K(+)] was measured up to 60 min. Patients were monitored for hypoglycemia and EKG changes. RESULTS: Baseline serum [K(+)] was 6.01 ± 0.87 and 6.23 ± 1.20 mmol/l in the insulin and glucose-only groups, respectively (p = 0.45). At 60 min, the glucose-only group had a fall in [K(+)] of 0.50 ± 0.31 mmol/l (p < 0.001). In the insulin group, there was a fall of 0.83 ± 0.53 mmol/l at 60 min (p < 0.001) and a lower serum [K(+)] at that time compared to the glucose-only group (5.18 ± 0.76 vs. 5.73 ± 1.12 mmol/l, respectively; p = 0.01). In the glucose-only group, the glucose area under the curve (AUC) was greater and the insulin AUC was smaller. Two patients in the insulin group developed hypoglycemia. CONCLUSION: Infusion of a glucose-only bolus caused a clinically significant decrease in serum [K(+)] without any episodes of hypoglycemia.
Asunto(s)
Glucosa/administración & dosificación , Hiperpotasemia/complicaciones , Hiperpotasemia/tratamiento farmacológico , Insulina/administración & dosificación , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Administración Intravenosa , Adulto , Estudios Cruzados , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glucosa/uso terapéutico , Humanos , Insulina/uso terapéutico , Masculino , Potasio/sangre , Diálisis Renal/métodos , Resultado del TratamientoRESUMEN
Monoclonal serum free light chain measurements are used to follow up and manage patients with monoclonal gammopathies, and abnormal serum free light chain ratios are associated with risk of progression in certain diseases. We aimed to validate the reference intervals in our population. Reference intervals for κ and λ free light chains were established on 120 healthy adults. Creatinine levels were measured to exclude renal dysfunction and serum protein electrophoresis was performed. All creatinine values were within normal limits. After exclusion of subjects with abnormal serum protein electrophoreses, 113 subjects were available for analysis. The 95% reference interval was 6.3-20.6 mg/L for κ free light chains, 8.7-25.9 mg/L for λ free light chains and 0.46-1.23 for free light chain ratio. Most of the values fell within the manufacturer's recommended limits and therefore could be used for our population.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Paraproteinemias/sangre , Adulto , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Suero/inmunología , Sudáfrica , Adulto JovenRESUMEN
BACKGROUND: Population-based data on the burden of chronic kidney disease (CKD) in sub-Saharan Africa is still very limited. We assessed the prevalence and determinants of CKD, and evaluated the concordance of commonly advocated estimators of glomerular filtration rate (eGFR) in a mixed ancestry population from South Africa. METHODS: Participants were a population-based sample of adults selected from the Bellville-South community in the metropolitan city of Cape Town. eGFR was based on the Cockroft-Gault (CG), Modification of Diet in Kidney Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations (with and without adjustment for ethnicity). Kidney function staging used the Kidney Disease Outcome Quality Initiative (KDOQI) classification. Logistic regressions and kappa statistic were used to investigate determinants of CKD and assess the agreement between different estimators. RESULTS: The crude prevalence of CKD stage 3-5 was 14.8% for Cockcroft-Gault, 7.6% and 23.9% respectively for the MDRD with and without ethnicity correction, and 7.4% and 17.3% for the CKD-EPI equations with and without ethnicity correction. The highest agreement between GFR estimators was between MDRD and CKD-EPI equations, both with ethnicity correction, Kappa 0.91 (95% CI: 0.86-0.95), correlation coefficient 0.95 (95% CI: 0.94-0.96). In multivariable logistic regression models, sex, age and known hypertension were consistently associated with CKD stage 3-5 across the 5 estimators. CONCLUSIONS: The prevalence of CKD stages greater than 3 is the highest reported in Africa. This study provides evidence for support of the CKD-EPI equation for eGFR reporting and CKD classification.
Asunto(s)
Pueblo Asiatico/etnología , Población Negra/etnología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/etnología , Población Blanca/etnología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Sudáfrica/etnologíaRESUMEN
OBJECTIVE: Metabolic syndrome (MetS) and its associated cardiovascular risk are on the increase in children. High-sensitivity C-reactive protein (hs-CRP) has emerged as a useful marker for inflammation associated with atherosclerosis and cardiovascular disease. Our aim was to determine the distribution of hs-CRP in an effort to identify the MetS variable that is critical in modulating plasma CRP levels in a population of South African adolescents. DESIGN: A cross-sectional analytical study design was used for this investigation, where the dependent and independent variables were measured simultaneously. METHODS: Anthropometric variables, blood pressure, fasting blood glucose and lipids were performed on 324 consenting learners aged 15-18 years from three different ethnic groups (Black, White and Coloured). The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) for ages 15-18 year olds was used to define MetS. RESULTS: The prevalence of MetS and obesity was 3.7% and 7.1%, respectively. The hs-CRP levels were significantly higher in subjects with a waist-circumference greater than the 90th percentile (p < 0.01) and in obese learners with MetS, but was lower in adolescents with normal weight and MetS. Median hs-CRP levels increased with an increasing number of metabolic abnormalities and exceeded 3 mg/L in 19% of adolescents. Gender and ethnic differences were observed. CONCLUSION: Our findings suggest that obesity and waist circumference appear to be major mediators of hs-CRP levels in South African adolescents.
RESUMEN
Iron is a vital element in the multifactorial initiation of myelination. It is required for cholesterol and lipid biosynthesis, both key components of myelin. Iron also plays an important role in energy production by mitochondrial oxidative metabolism which occurs in myelin-producing oligodentrocytes at a higher rate than in any other cell. Iron deficiency can, therefore, result in decreased oligodendrocyte survival and defective myelination. This led us to investigate iron status in 2 consecutive children with multiple sclerosis who presented with recurrent episodes of tumefactive demyelination. Testing revealed nonanemic iron deficiency in both patients. Discontinuation of iron supplementation in both children resulted in recurrent decreased iron parameters which can indicate mutations in proteins responsible for regulation of iron uptake. Further studies are warranted to explore the association of low iron in children presenting with recurrent episodes of tumefactive demyelination.
Asunto(s)
Corteza Cerebral/patología , Enfermedades Desmielinizantes/sangre , Hierro/sangre , Preescolar , Enfermedades Desmielinizantes/patología , Hemoglobinas/metabolismo , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , RecurrenciaRESUMEN
BACKGROUND: Critical result reporting is a requirement for accreditation by accreditation bodies worldwide. Accurate, prompt communication of results to the clinician by the laboratory is of extreme importance. Repeating of the critical result by the recipient has been used as a means to improve the accuracy of notification. Our objective was to assess the accuracy of notification of critical chemical pathology laboratory results telephoned out to clinicians/clinical areas. We hypothesize that read-back of telephoned critical laboratory results by the recipient may improve the accuracy of the notification. METHODS: This was a prospective study, where all critical results telephoned by chemical pathologists and registrars at Tygerberg Hospital were monitored for one month. The recipient was required to repeat the result (patient name, folder number and test results). Any error, as well as the designation of the recipient was logged. RESULTS: Of 472 outgoing telephone calls, 51 errors were detected (error rate 10.8%). Most errors were made when recording the folder number (64.7%), with incorrect patient name being the lowest (5.9%). Calls to the clinicians had the highest error rate (20%), most of them being the omission of recording folder numbers. CONCLUSION: Our audit highlights the potential errors during the post-analytical phase of laboratory testing. The importance of critical result reporting is still poorly recognized in South Africa. Implementation of a uniform accredited practice for communication of critical results can reduce error and improve patient safety.