Severe tracheal and bronchial collapse in adults with type II mucopolysaccharidosis

Abstract

BackgroundMucopolysaccharidosis type II (MPSII) patients frequently suffer from dyspnoea caused by restrictive airway disease due to skeletal abnormalities as well as glycosaminoglycans (GAG) accumulation at different levels of the airway, including the trachea. In this study we describe the extent of the tracheal and bronchial narrowing, the changes in airway diameter during respiration and the effects of these obstructions on respiratory function in adult MPSII patients.MethodsFive adult MPSII patients (mean age 40 years) were included. Pulmonary function tests and in- and expiratory chest CT scans were obtained. Cross-sectional areas of trachea and main bronchi were measured at end-inspiration and -expiration and percentage collapse was calculated.ResultsThere was diffuse narrowing of the entire intra-thoracic trachea and main bronchi and severe expiratory collapse of the trachea in all patients. At 1 cm above the aortic arch the median % collapse of the trachea was 68 (range 60 to 77 %), at the level of the aortic arch 64 (range 21–93 %), for the main bronchi this was 58 (range 26–66 %) on the left and 44 (range 9–76 %) on the right side. The pulmonary function tests showed that this airway collapse results in obstructive airway disease in all patients, which was severe (forced expiratory volume <50 % of predicted) in four out of five patients.ConclusionIn adult MPS II patients, central airways diameters are strikingly reduced and upon expiration there is extensive collapse of the trachea and main bronchi. This central airways obstruction explains the severe respiratory symptoms in MPSII patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0425-z) contains supplementary material, which is available to authorized users.

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…AHI and OSAs, when evaluated, seem to be reduced by ERT, but it is clear that macroglossia and adeno-tonsils hypertrophy are not modified during long-term treatment [36,45,46,49,50,[61][62][63][64]. Although only few cases are reported, it appears that ERTs do not act on deformities of trachea, bronchi and vessels [65][66][67][68][81][82][83][84]. In the first years after ERT availability it seemed that it could have a "stabilization" role on hearing loss and corneal clouding but unfortunately the different articles do not agree on this point and the final impression is that hearing and eyes are among the difficult-to-reach targets for ERT [42,47,59,60,[85][86][87][88][89][90].…”

“…Tracheobronchomalacia is a frequent finding in MPSs, mainly in MPS II and IVA [65,[136][137][138][139], substantially contributing to an increased risk while undergoing anesthesiological procedures. It is due both to an intrinsically malacic trachea and to external compression by mediastinal deposition of GAGs or a tortuous brachiocephalic artery [65][66][67][68]136,137,139], in the context of disproportionate growth of the thoracic cage. During the years of observation of ERT-treated MPS patients, it has become clear that ERT is not effective neither on tracheal cartilage deformities nor in clearing the extrinsic mediastinal storage [65][66][67][68].…”

“…It is due both to an intrinsically malacic trachea and to external compression by mediastinal deposition of GAGs or a tortuous brachiocephalic artery [65][66][67][68]136,137,139], in the context of disproportionate growth of the thoracic cage. During the years of observation of ERT-treated MPS patients, it has become clear that ERT is not effective neither on tracheal cartilage deformities nor in clearing the extrinsic mediastinal storage [65][66][67][68]. Nevertheless, improvements were seen in spirometric evaluations (FEV1, FVC and MVV) according to most of the long-term studies [36][37][38]43,49,[69][70][71][72].…”

Genotype–phenotype relationship in mucopolysaccharidosis II: predictive power of IDS variants for the neuronopathic phenotype

“…The IDS gene encodes a lysosomal enzyme, and deficiency causes accumulation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate in multiple organs. Clinical characteristics include abnormalities in the respiratory tract, central nervous system (CNS), cardiac valves, and the size of the liver and spleen . There are two major phenotypes with respect to CNS involvement.…”

“…Clinical characteristics include abnormalities in the respiratory tract, central nervous system (CNS), cardiac valves, and the size of the liver and spleen. 1,2 There are two major phenotypes with respect to CNS involvement. In the neuronopathic form, patients develop a progressive intellectual disability that becomes apparent at the age of 3 to 5 years.…”