ABSTRACT
Type 1 Portuguese Familial Amyloid Polyneuropathy was first observed in 1939 and described in 1951 by Corino Andrade. FAP is a rare autosomal dominant disease caused by a mutant gene in chromosome 18, characterized by a variant transthyretin in which valine is substituted for methionine at position 30 (ATTR V30M), affecting mainly young adults. ATTR V30M positivity does not imply disease, but the disease is only present with ATTR V30M in serum. The clinical manifestations of FAP on the pelvic floor and genitourinary system are frequent at early disease onset. Phenotypic diversity can depend on modulating agents in the deposition of the mutant TTR, such as incomplete penetration and environmental influence. Functional vesicourethral disorders appear to be primarily at the bladder filling phase, namely diminished bladder sensation, and associated with a decrease in detrusor contractility during the emptying phase. Unbalanced voiding takes place in this context, with high post-void residuals, increasing the rate of co-morbidity, namely recurrent urinary tract infections and chronic renal failure.This study describes the lower urinary tract dysfunctions in ATTR V30M positive carriers, particularly during the asymptomatic period and early stages of the disease, and additionaly it describes its association with the clinical evolution of the disease. In the preliminary phase of the study, the lower urinary tract dysfunction in FAP-women may present itself as an early manifestation in asymptomatic patients. Uroflowmetry and the evaluation of post-voiding residual volume are non-invasive and low cost tests that should be done during routine initial evaluation. Reduced bladder sensation and poor detrusor contractility may be considered initial markers of FAP. The neurogenic factor (bladder afferent neurons) appears to be mechanical in nature with myogenic repercussions. This further aggravates the bladder underactivity secondary to pelvic efferent parasympathetic neuropathy and amyloid infiltration in the bladder wall. Early diagnostic and therapeutic intervention may avoid secondary end stage renal disease.
Subject(s)
Amyloid Neuropathies, Familial/complications , Lower Urinary Tract Symptoms/etiology , Adult , Amino Acid Substitution , Amyloid Neuropathies, Familial/genetics , Amyloid Neuropathies, Familial/psychology , Biomarkers , Disease Progression , Female , Heterozygote , Humans , Neurologic Examination , Prealbumin/genetics , Quality of Life , Urinary Incontinence/epidemiology , Urinary Incontinence/etiology , UrodynamicsABSTRACT
La polineuropatia amiloidea portuguesa (FAP) tipo I, fue observada por primera vez en 1939 y descrita en 1951 por Corino Andrade. La FAP es una enfermedad rara autonómica dominante, causada por una mutación genética del cromosoma 18, y caracterizada por la variación del la transretina, donde la valina es sustituida por metionina en la posición 30 (ATTRV 30 M) afectando principalmente a adultos jóvenes. La positiviadad de ATTRV 30 M no implica enfermedad. La enfermedad esta presente unicamente cuando el ATTR 30 M se encuentra en la sangre. Las manifestaciones de la FAP en el suelo pelvico y sistema genitourinario, son frecuentes al comienzo de la enfermedad. La diversidad fenotípica puede depender de diversos factores, modulando la mutación TTR, tal como penetración incompleta e influencia del ambiente. Las alteraciones funcionales del tracto urinario inferior aparecen en primer lugar en la fase de llenado vesical, principalmente con sensación vesical disminuida, y asociada con una afectación de la contractilidad del detrusor en la fase del vaciado. En este contexto aparece una micción descompensada, con residuos postmiccionales altos, incrementando la comorbilidad, principalmente de infecciones del tracto urinario e insuficiencia renal crónica. Este estudio describe las disfunciones del tracto urinario inferior en portadores positivos de ATTRV 30 M, sobre todo durante el periodo asintomático y estadios tempranos de la enfermedad, así como expone su asociación con la evolución clínica. En la fase preliminar del estudio, la disfunción del tracto urinario inferior en las mujeres con FAP, puede presentarse como una manifestación temprana en pacientes asintomáticos. La flujometría y la medida del residuo postmiccional son test no invasivos, y de bajo coste, que deberían hacerse durante la evaluación inicial rutinaria. La disminución de la sensibilidad vesical y afectación de la contractilidad del detrusor pueden considerarse como marcadores iniciales de la FAP. El factor neurogénico (elemento aferente) parece ser de naturaleza mecánica con repercusiones miogénicas. Esto último agrava un detrusor hipoactivo secundario a una neuropatía parasimpatica eferente e infiltración amiloide de la pared vesical. Un diagnostico precoz, así como una terapeutica temprana podrían evitar una enfermedad renal terminal
Type 1 Portuguese Familial Amyloid Polyneuropathy was first observed in 1939 and described in 1951 by Corino Andrade. FAP is a rare autosomal dominant disease caused by a mutant gene in chromosome 18, characterized by a variant transthyretin in which valine is substituted for methionine at position 30 (ATTR V30M), affecting mainly young adults. ATTR V30M positivity does not imply disease, but the disease is only present with ATTR V30M in serum. The clinical manifestations of FAP on the pelvic floor and genitourinary system are frequent at early disease onset. Phenotypic diversity can depend on modulating agents in the deposition of the mutant TTR, such as incomplete penetration and environmental influence. Functional vesicourethral disorders appear to be primarily at the bladder filling phase, namely diminished bladder sensation, and associated with a decrease in detrusor contractility during the emptying phase. Unbalanced voiding takes place in this context, with high post-void residuals, increasing the rate of co-morbidity, namely recurrent urinary tract infections and chronic renal failure. This study describes the lower urinary tract dysfunctions in ATTR V30M positive carriers, particularly during the asymptomatic period and early stages of the disease , and additionaly it describes its association with the clinical evolution of the disease. In the preliminary phase of the study, the lower urinary tract dysfunction in FAP-women may present itself as an early manifestation in asymptomatic patients. Uroflowmetry and the evaluation of post-voiding residual volume are non-invasive and low cost tests that should be done during routine initial evaluation. Reduced bladder sensation and poor detrusor contractility may be considered initial markers of FAP. The neurogenic factor (bladder afferent neurons) appears to be mechanical in nature with myogenic repercussions. This further aggravates the bladder underactivity secondary to pelvic efferent parasympathetic neuropathy and amyloid infiltration in the bladder wall. Early diagnostic and therapeutic intervention may avoid secondary end stage renal disease
