Seguimento de cinco anos do envolvimento do sistema respiratório em pacientes com doença de Pompe de início tardio em terapia de reposição enzimática irregular no estado do Ceará

Abstract

INTRODUCTION: Pompe disease (PD), also known as type II glycogen deposition disease, is a rare autosomal recessive hereditary disorder characterized by a deficiency in the enzyme α-glucosidase acid (AGA). This failure causes the accumulation of glycogen in tissues of the skeletal and respiratory muscles. It is presented in forms: infant, juvenile and adult (late onset). In late-onset Pompe disease (LOPD) the diaphragm and the paraspinal axial musclesare often involved. Enzyme Replacement Therapy (ERT) is the only current treatment. Little is known about pulmonary manifestations in PD in Brazil, contributing to the management difficulty in this population. OBJECTIVES: To describe a series of cases of five patients with LOPDin the state of Cearaduring five years of outpatient follow-up with the objectives of: Characterizing the respiratory and motor involvement at the time of diagnosis and its evolution in the study period; To describe and analyze theimpact of unprogrammed interruptions of ERT on respiratory and motor involvement by analyzing the behavior of the following variables: Spirometric parameters -Forced Vital Capacity (FVC), Forced Expiratory Volume in the 1st Second (FEV1), Expiratory Flow Peak ), Tiffenau Index (FEV1/ FVC); Maximum respiratory pressures -Maximum Inspiratory and Expiratory Pressures (MIPand MEP); Motor function: Global Muscle Forcesand Palmar Hold, dyspnea and exercise tolerance: Walk Test 6 Minutes (distance,peripheral oxygen saturation, dyspnea sensation and fatigue in the lower limbs). And, evaluate the correlation of pulmonary function parameters that correlate with diaphragmatic dysfunction measured by the percentage difference of FVC in the sitting and lying positions. METHOD: This was a prospective, descriptive and observational cohort study in humans. The study was carried out at Resplab and the Walter Cantídio University Hospital of the Federal University of Cearafrom December 2012 to July 2018. The population was composed of five patients with a confirmed molecular diagnosis of LOPDwith indication of ERTin the State of Ceara. Adult patients, older than 18 years, of both genders were included. The respiratory function (spirometry) and the maximum respiratory pressures were evaluated in the sitting and lying positions; chest X-ray; evaluation of the diaphragmatic thickness, through examination of MRI and high resolution chest computed tomography (HRCT), transdiaphragmatic pressure measurement (Pdi), functional evolution (six-minute walk test -6MWT); with outpatient follow-up and monitoring of patientsERT. The study was approved by the Ethics Committee in Institutional Research and under opinion nº 1,867,794. RESULTS AND CONCLUSIONS: The most common clinical complaint was weakness of lower limb muscles followed by muscle pain. A motor deficit was especially noticed in the muscles of the lower limbs and the axial musculature of the five patients. The respiratory involvement of the LOPDwas variable, depending directly on the time of the disease. Two patients with the greatest respiratory compromise had a paradoxical respiratory movement. The impairment of diaphragmatic function in these cases was greater than the motor involvement itself in two of the five individuals and was associated with the need for noninvasive ventilation (NIV) at night. The ERTpromoted improvement or stability of the evolution of FVC and other spirometric parameters confirming that this is the best parameter for evaluation and follow-up of respiratory involvement. The assessment of global motor strength by the MRC scale was shown to be better for the follow-up of LOPD progression than the measurement of palmar grip strength. Periods of ERT interruptions, especially if prolonged, compromised the response to treatment, with partial or total functional recovery after resumption of treatment. The maximum respiratory pressures did not vary correspondingly to the changes in FVC nor the parameters measured in the 6-minute walk test, which were possibly less useful for evaluating the ERTresponse than the FVC measured in the sitting and lying positions. The measurement of the difference in PEF in the sitting and lying positions correlates with the corresponding measure for FVC, and maybe object of study in future studies.