Fabry disease in Spain: description of Spanish patients and a comparison with other European countries using data from the Fabry Outcome Survey (FOS).

AIMS: Fabry disease (FD) is an X-chromosome-linked transmitted lysosomal storage disorder as a result of the deficient activity of enzyme α-galactosidase A. This leads to accumulation of neutral glycosphingolipids associated with organ involvement and premature death. We report the clinical characteristics of Spanish patients enrolled on the Fabry Outcome Survey (FOS; an international multicentre registry for the disease) and also compare these data with those from the rest of Europe. METHODS: Baseline clinical data of 92 patients (41 males and 51 females) are described and analysed globally and according to gender. We compare the data of Spanish patients with those previously published from the rest of Europe patients in FOS. RESULTS: Mean age of onset of symptoms in men was 20, and 24 years in women, with a mean delay of 11 years to the diagnosis in both genders. The predominant clinical involvement in male patients was renal (69%), cardiac (66%) and neurological (60%), and for female patients, it was neurological (42%), cardiac (33%), keratopathy (30%) and nephropathy (28%). Disease severity was significantly higher in male patients. Compared to the rest of European FOS-patients, Spanish patients were diagnosed at an earlier age with a smaller proportion of disease-related involvement for most organ irrespective of gender, though not its global severity in male patients. CONCLUSIONS: We present the largest cohort of Spanish patients diagnosed with FD. The pattern of involvement (though not its global severity) could be different in Spanish patients in comparison with others from Europe. Expanding the knowledge of FD will permit early diagnosis as well as the possibility of starting the specific treatment.

Age adjusting severity scores for Anderson-Fabry disease.

Anderson-Fabry Disease (AFD) is a life-threatening X-linked lysosomal storage disorder, caused by a deficiency of alpha galactosidase A. The disease affects males and females, and may present in childhood or adulthood. In the absence of a biomarker of disease burden or therapeutic response, scoring systems based on clinical manifestations, have been developed. Such global scores e.g. the Mainz Severity Score Index (MSSI) are confounded by the natural history of disease that deteriorates with age, making comparisons across age groups invalid. In this study the baseline MSSI, as adapted for data collected in the Fabry Outcome Survey (FOS) database (FOS-MSSI), was calculated for 655 females and 617 males with confirmed AFD. Using an ANCOVA model, equations for the predicted FOS-MSSI based on age were derived for males and females from data where patients from the UK or outside Europe were excluded. The initially excluded patients were used for validation. The predicted severity scores of UK and non-Europe-cohorts of adult and paediatric patients were found to follow the model produced for the European cohort thereby providing validation of the methodology. Deviation of the actual FOS-MSSI from the predicted was calculated and termed the age-adjusted score. Examples of the use of the age-adjusted score in individual patients, in comparison of mutations and in investigation of early factors which may impact on later severity of Fabry disease are given. This validated age and gender adjusted scoring system allows the comparison of disease severity in different subgroups such as genotypes without age or sex as confounding factors.

Does geographical location influence the phenotype of Fabry disease in women in Europe?

This study examines the relationship between phenotype and geographical location of patients with Fabry disease in Europe. Data were taken from patients enrolled in the Fabry Outcome Survey (FOS), as of October 2007. A modified version of the Mainz Severity Score Index (FOS-MSSI) was used to classify patients according to the severity of disease. European patients were grouped depending on country of residence (northern or southern European countries). Results are presented from 762 patients enrolled in FOS in Europe (357 men and 405 women); 66% lived in northern and 34% in southern countries. Median age at onset of symptoms of Fabry disease was similar in both sexes. No differences in disease severity were seen among men, according to place of residence; however, women living in northern countries had higher severity scores (p < 0.001) than those in southern countries. In men and women, FOS-MSSI scores increased with age, irrespective of place of residence. The results suggest that expression of different phenotypic features in Fabry disease in women living in Europe may be influenced by extra-genetic or epigenetic factors. These factors might be related to dietary or environmental influences that differ according to the patient's country of residence.

Natural history of Fabry disease in females in the Fabry Outcome Survey.

BACKGROUND: Fabry disease is a rare X linked lysosomal storage disorder resulting from deficiency of alpha-galactosidase A activity. Although the severity of clinical features in male patients is well described, only recently have studies reported the high prevalence of disabling clinical features in heterozygous females. AIMS: This study sets out to examine the clinical features and natural history of Fabry disease in further detail in a large group of female patients. METHODS: Data were obtained from 303 females enrolled in the Fabry Outcome Survey. Pain was assessed using the Brief Pain Inventory, and health related quality of life (HRQoL) was assessed using the European Quality of Life Questionnaire. A modified version of the Mainz Severity Score Index was also applied. Data on left ventricular mass (LVM) index, mean ventricular wall thickness, and glomerular filtration rate (GFR) were used to assess cardiac and renal involvement. RESULTS: The most commonly reported clinical features in females were neurological (77%) and cardiac (59%). A history of renal involvement was recorded in 40% of cases. Neurological features were the earliest to develop (mean age: 16 years), whereas cardiac (mean age: 33.5 years) and renal (mean age: 37.3 years) features developed later. LVM index increased exponentially with age. In addition, age was negatively correlated with estimated GFR and HRQoL. CONCLUSIONS: Females with Fabry disease report important age related clinical features and clinical investigation demonstrates evidence of disease progression. This study highlights the importance of careful and longitudinal assessment of female heterozygote patients with Fabry disease.

Feocromocitoma del órgano de Zuckerkandl. A propósito de un caso / Pheochromocytoma of the organ of Zuckerkandl. Regarding a case

INTRODUCCIÓN: Los feocromocitomas extra-adrenales representan el 17-18 per cent de todos los feocromocitomas, siendo el 85 per cent de éstos de localización infradiafragmática y generalmente donde pueda hallarse tejido cromafin, como en el caso que se presenta, ubicado en el órgano de Zuckerkandl. Pueden aparecer, asimismo, en el contexto de síndromes familiares como las facomatosis o los MEN (IIA y IIB). CASO CLÍNICO: Presentamos un caso de feocromocitoma localizado en el órgano de Zuckerkandl que se diagnostica en el estudio de una HTA mal controlada. El diagnóstico se realizó mediante pruebas analíticas (metanefrinas) y radiológicas (ecografía, TAC y MIBG-I131). El paciente fue tratado quirúrgicamente mediante exéresis de la lesión, previo bloqueo y adrenérgico con fenoxibenzamina y propanolol. En la actualidad el paciente se encuentra asintomático con niveles tensionales y parámetros analíticos normales. DISCUSIÓN: Los feocromocitomas extra-adrenales se suelen localizar en la región infradiafragmática para-aórtica superior. Su grado de malignidad se debe establecer mediante los hallazgos histopatológicos, las recidivas locales y la aparición de metástasis a distancia. Tras la sospecha clínica y el descubrimiento de una masa retroperitoneal por ecografía, TAC y/o RMN, se debe realizar gammagrafía con MIBG-I131 para confirmar el diagnóstico, así como para descartar posibles tumores a distancia. El tratamiento es la cirugía previo bloqueo de la secreción de catecolaminas mediante la administración preoperatoria de alfabloqueantes, con o sin betabloqueantes (AU)

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Bacteriemia por Citrobacter freundii: presentación de dos casos / Bacteremia caused by Ctrobacter freundii: review

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