Pulmonary involvement in Fabry disease: Overview and perspectives

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of alphagalactosidase A, which leads to storage of sphingolipids in virtually all human cells and consequently to organ dysfunction. Pulmonary involvement is still debated. But, obstructive lung disease is up to ten times more prevalent in patients with FD compared to general public. Also, an accelerated decline in forced expiratory volume in one second (FEV1) over time was observed in these patients. Lysosomal storage of glycosphingolipids is considered leading to small airway disease via hyperplasia of the bronchiolar smooth muscle cells. Larger airways may become involved with ongoing disease process. There is no evidence for involvement of the lung interstitium in FD. The effect of enzyme replacement therapy on respiratory involvement remains to be determined in large, prospective controlled trials. AbstractFabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of alpha-

Sleep Disturbance, Obstructive Sleep Apnoea and Abnormal Periodic Leg Movements: Very Common Problems in Fabry Disease

“…Symptoms include dyspnoea in up to 69% of men and 65% of women (Mehta et al 2004), cough, wheeze, reduced exercise tolerance (Lobo et al 2008;Germain 2010) and fatigue (Lobo et al 2008;Franzen et al 2013). Obstructive airway disease has been reported in up to 26% of women and 61% of men (Rosenberg et al 1980;Germain 2010;Franzen et al 2013).…”

“…In men, a significant decrease in all spirometric variables, including a reduced diffusion capacity, has been observed compared with unaffected controls (Magage et al 2007), while women have decreased percent fixed vital capacity. The primary mechanism is likely to be Gb3 accumulation within the endothelial and bronchial smooth muscle cells resulting in hyperplasia of the pulmonary small airways combined with impaired smooth muscle relaxation (Magage et al 2007;Raiman and Clarke 2010;Franzen et al 2013).…”

“…Furthermore, 2.7% of the population meet criteria for clinically significant restless leg syndrome (Winkelman et al 2013). Enzyme replacement therapy in Fabry disease has been shown to stabilise or alleviate bronchial obstruction and sleep apnoea (Franzen et al 2013;Wang et al 2008;Kim et al 2007) and reduce neuropathic pain (Dominguez et al 2007).…”

Lungenbeteiligung bei erwachsenen Patienten mit angeborenen Stoffwechselerkrankungen

“…Typische Symptome der Betroffenen sind Dyspnoe, Giemen und trockener Husten ohne gleichzeitige schwere kardiale Probleme [39,42]. In einer kürzlich veröffentlichten Übersichtsarbeit untersuchten Franzen et al [43] [45]. Der Schweregrad der Bronchialobstruktion ist abhängig vom Alter und männlichen Geschlecht.…”

“…Manche Frauen scheinen jedoch genauso schwer betroffen zu sein wie männliche Patienten -lediglich zehn Jahre später, was der Beteiligung anderer Organe bei heterozygoten Patienten entspricht. Die Datenlage zur Schwere der Atemwegsobstruktion und Raucheranamnese ist uneinheitlich [39,43]. Zugrunde liegender Pathomechanismus der Erkrankung der kleinen bis mittleren Atemwege bei M. Fabry ist wahrscheinlich eine Hyperplasie der glatten Muskelzellen innerhalb der Bronchien und Bronchiolen.…”