ABSTRACT
Fabry disease (FD) is an X-linked hereditary disease. It results from mutations in the GLA gene, leading to deficient activity of the enzyme alpha-galactosidase A (α-Gal A) and progressive accumulation of undegraded glycosphingolipids in cell lysosomes. Enzyme replacement therapy (ERT) can improve the natural course of this disease, but an early diagnosis is crucial for a successful treatment. We describe the case of a female diagnosed with chronic proteinuric kidney disease in the postpartum period. Despite receiving optimal medical treatment, the disease progressed and she started renal replacement therapy (RRT) with peritoneal dialysis (PD). Five years later, she was enrolled in a pilot screening study for FD, and the heterozygous mutation c.870G>C (p.Met290Ile; M290I) in exon six of the GLA gene was found. The family screening revealed the presence of this mutation in the patient's father and daughter. The proband did not meet the criteria for a definitive FD diagnosis, but she remained under follow-up at our nephrology metabolic diseases consultation, as the mutation was described as pathogenic and associated with a classic FD phenotype. Later that same year, reassessment exams revealed a worsening left ventricle mass index (LVMi), a new ischemic cerebral lesion, and a substantial increase in serum globotriaosylsphingosine (LysoGb3) levels. These clinical changes led to a decision to initiate ERT. p.M290I is a previously known but poorly described GLA mutation. To our knowledge, this is the first report of p.M290I mutation-associated disease activity that offers strong evidence of its pathogenicity.
ABSTRACT
Membranous nephropathy is the most common cause of nephrotic syndrome in adults. A non-negligible number of cases are associated with systemic conditions. We report a case of a 50-year-old man who presented with nephrotic syndrome six months after being diagnosed with celiac disease. Although the patient showed disappearance of circulating immunoglobulin A (IgA) anti-tissue transglutaminase antibodies following a gluten-free diet, he had a sudden onset of nephrotic syndrome presenting with severe hypoalbuminemia. Other secondary causes were promptly excluded leading to the assumption of celiac disease-associated membranous nephropathy with remission after treatment with angiotensin system blockade and a gluten-free diet. The goal of this case report is to alert the clinic towards this rare association aiming for an early diagnosis and adequate selection of long-term therapy.
ABSTRACT
Fabry disease (FD) is an X-linked, systemic lysosomal deposition disease caused by alpha-galactosidase A (AGAL) enzyme deficiency deriving out of changes on the GLA gene. Though several mutations have been described, one must consider that even a specific mutation may present with variable clinical expression within the same family. Typically described as a disease that affects hemizygous men with no residual AGAL activity, we describe a novel FD mutation (first case of GLA T194A variant worldwide) in a 49-year-old woman presenting with a classic phenotype of FD. The patient investigation highlighted a previously not described mutation in exon 4 of the GLA gene, as for the substitution of threonine for alanine. The same mutation was identified in her children, one of them presenting with end-stage kidney disease (ESKD) in early adulthood.
Subject(s)
Fabry Disease , Adult , Child , Fabry Disease/diagnosis , Fabry Disease/genetics , Female , Humans , Male , Middle Aged , Mutation , Mutation, Missense , Phenotype , alpha-Galactosidase/geneticsABSTRACT
Introducción: La sexualidad, el estatus psicosocial y la calidad de vida (QoL) son factores importantes, a menudo infravalorados, en los esquemas de diálisis. Objetivos: Evaluar la prevalencia de disfunción sexual y sus asociaciones en los pacientes en diálisis peritoneal (DP). Métodos: Se utilizaron el Índice de Función Sexual Femenina (IFSF), el Índice Internacional de Función Eréctil (IIFE), la Escala de Ansiedad y Depresión Hospitalaria (HADS) y los cuestionarios sobre calidad de vida EQ5D en la población prevalente en DP (57 pacientes). Se realizaron análisis multivariantes para investigar los factores clínicos independientes para disfunción sexual. Resultados: Se diagnosticó disfunción sexual en el 67,9 % de las mujeres y en el 44,8 % de los varones. En las mujeres la albúmina sérica, la creatinina, los niveles de fósforo y EQ5D se relacionaran positivamente con IFSF. En los varones existía una correlación negativa entre el calcio sérico y el score IIEF. En el análisis multivariante los parámetros nutricionales permanecieron asociados de manera independiente con la disfunción sexual en mujeres; en los varones los principales determinantes fueron el aumento de la concentración de calcio y la disminución de la testosterona. En los análisis de regresión logística el riesgo de disfunción sexual en la población global está asociado a niveles menores de albúmina (OR = 6,94) y a un score inferior de EQ5D (OR = 6,93). Conclusiones: La disfunción sexual tiene una alta prevalencia y una fuerte asociación con la percepción de la calidad de vida de los pacientes en DP. Se han encontrado diferentes variables clínicas relacionadas con la disfunción sexual en cada sexo que justifican actitudes preventivas y terapéuticas individualizadas (AU)
Background: Sexual function, psychosocial status and quality of life (QoL) are important dimensions, often underestimated, in dialysis treatment schedules. Objectives: The aim of this study was to evaluate the prevalence of sexual dysfunction and its associations, among peritoneal dialysis (PD) patients. Methods: The Index of Female Sexual Function (IFSF), the International Index of Erectile Function (IIEF), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life EQ5D questionnaires were applied to a prevalent PD population of 57 enrolled patients. Multivariate analysis was conducted to investigate clinical independent risk factors for sexual dysfunction. Results: Sexual dysfunction was diagnosed in 67.9% of women and 44.8% of men. In females, serum albumin, creatinine and phosphorus levels and EQ5D positively correlated with IFSF score. For males, there was a significant negative correlation between serum calcium levels and the IIEF score. On multivariate analysis, nutritional parameters remained independently associated with sexual dysfunction in women; in males, increase in calcium concentration and decrease of testosterone were main determinants. On logistic regression analysis, the risk of sexual dysfunction in global population was associated with lower values of albumin (OR=6.94) and with a lower QoL score EQ5D (OR=6.93). Conclusions: Sexual dysfunction is highly prevalent and strongly associated with impaired QoL of PD patients. Different clinical variables were related to sexual dysfunction in each gender, justifying an individualized preventive and therapeutic approaches (AU)
Subject(s)
Humans , Male , Female , Sexual Dysfunction, Physiological/epidemiology , Renal Insufficiency, Chronic/therapy , Peritoneal Dialysis/adverse effects , Quality of Life , Sickness Impact Profile , Psychometrics/instrumentation , Age and Sex Distribution , Anxiety/epidemiology , Depression/epidemiologyABSTRACT
BACKGROUND: Sexual function, psychosocial status and quality of life (QoL) are important dimensions, often underestimated, in dialysis treatment schedules. OBJECTIVES: The aim of this study was to evaluate the prevalence of sexual dysfunction and its associations, among peritoneal dialysis (PD) patients. METHODS: The Index of Female Sexual Function (IFSF), the International Index of Erectile Function (IIEF), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life EQ5D questionnaires were applied to a prevalent PD population of 57 enrolled patients. Multivariate analysis was conducted to investigate clinical independent risk factors for sexual dysfunction. RESULTS: Sexual dysfunction was diagnosed in 67.9% of women and 44.8% of men. In females, serum albumin, creatinine and phosphorus levels and EQ5D positively correlated with IFSF score. For males, there was a significant negative correlation between serum calcium levels and the IIEF score. On multivariate analysis, nutritional parameters remained independently associated with sexual dysfunction in women; in males, increase in calcium concentration and decrease of testosterone were main determinants. On logistic regression analysis, the risk of sexual dysfunction in global population was associated with lower values of albumin (OR=6.94) and with a lower QoL score EQ5D (OR=6.93). CONCLUSIONS: Sexual dysfunction is highly prevalent and strongly associated with impaired QoL of PD patients. Different clinical variables were related to sexual dysfunction in each gender, justifying an individualized preventive and therapeutic approaches.
