Transplante hepático em paciente portadora de doença de Niemann-Pick com envolvimento pulmonar

Abstract

Niemann-Pick disease (NPD) is a rare lysosomal storage disorder that is generalized and severe, as well as being characterized by intracellular sphingomyelin accumulation caused by deficiency of sphingomyelinase activity.(1)From a respiratory standpoint, the various types of NPD, including type B, can cause progressive loss of pulmonary function, with suggestive radiological findings. We report the case of a 27-year-old female patient with type B NPD. The patient was initially referred for outpatient treatment in 2003, presenting with a history of hepatosplenomegaly and delayed psychomotor development since childhood. The diagnosis of NPD was confirmed by measuring peripheral leukocyte sphingomyelinase activity, which was found to be decreased (0.009 nmol • h −1• mg −1 of protein; reference value, 0.745of protein). Serology for HIV, hepatitis B, and hepatitis C was negative, as was serology for syphilis (venereal disease research laboratory test). In addition, ANF was negative. Gaucher's disease was ruled out because beta-glucosidase levels were normal. The patient developed ascites and complained of mild dyspnea, being referred to the pulmonology clinic. She underwent a six-minute walk test (six-minute walk distance [6MWD] = 396 m; predicted 6MWD = 724 m), showing intense dyspnea at the end of the test (modified Borg scale score = 9) but no oxygen desaturation (SpO 2 = 97%). Spirometry results were suggestive of restrictive lung disease (FEV 1 = 1.77 L [61% of predicted]; FVC = 2.07 L [57% of predicted]; and FEV 1 /FVC ratio = 85%). A chest X-ray revealed no pulmonary changes. An HRCT scan revealed interlobular septal thickening in the bases and apices, together with right pleural effusion (Figures 1a and 1b). A rare entity, NPD is an autosomal recessive disorder characterized by abnormal accumulation of sphingomyelin in the reticuloendothelial system. Type B NPD has heterogeneous clinical manifestations and is mainly characterized by hepatosplenomegaly and progressive hypersplenism. Neurological involvement is rare; when it does occur, it is mild. The diagnosis is made by careful history taking and physical examination, as well as by determination of sphingomyelinase activity (which is decreased in peripheral leukocytes), together with fibroblast cell culture or analysis of bone marrow biopsy specimens revealing characteristic sea-blue histiocytes. There can be respiratory impairment secondary to macrophage and sphingomyelin accumulation in the distal airways and the alveoli, which leads to gradual deterioration of pulmonary function, reducing exercise tolerance. The clinical manifestations are heterogeneous, ranging from absence of symptoms to respiratory failure, and lung disease can progress to hypoxemia requiring oxygen therapy. (2,3)

Niemann-Pick disease type B: HRCT assessment of pulmonary involvement

“…The most commonly reported HRCT findings in the literature are smooth interlobular septal thickening and intralobular lines, predominantly in the lower lobes of the lungs, and focal or diffuse ground-glass opacities, also predominantly in the lower lung zones. 2 , 4 , 8 , 13 , 16 A crazy-paving pattern has also been reported. 3 , 4 In the literature, the changes seen on CT most commonly affect the lower lobes, bilaterally.…”

“… 3 , 4 , 7 Although a presumptive diagnosis can be made on the basis of clinical history and radiological findings, laboratory studies-measurement of sphingomyelinase activity in peripheral leukocytes together with fibroblast cell culture or analysis of bone marrow biopsy specimens revealing accumulation of lipid-filled macrophages (sea-blue histiocytes)-are definitive for the diagnosis. 8 In the present study, we analyzed HRCT scans from 13 patients with NPD type B, all of whom had histopathological confirmation. The objectives of the present study were to describe the most common HRCT findings and the major clinical and epidemiological characteristics observed in these patients.…”

Assistência Odontológica Ambulatorial De Pacientes Com Doença De Niemann-Pick Tipo B: Relato De Caso / Ambulatorial Dental Care for Patients With Niemann-Pick Type B Disease: Case Report

“…O diagnóstico é realizado por meio da anamnese bem detalha, aliada a exames complementares tais como: a realização da dosagem da atividade esfingomielinase, o teste de Filipin, que permite observar o acúmulo intracelular de colesterol; a aspiração da medula óssea, que revela o histiócito "azul-marinho" (MENDES et al, 2012;SANTOS et al, 2017). A DNP não possui cura.…”