Lung involvement and enzyme replacement therapy in Gaucher's disease

Abstract

Symptomatic lung involvement in Gaucher's disease is relatively rare, being restricted to patients with other severe manifestations. We describe our experience in eight of 411 patients in our referral clinic, who presented with prominent pulmonary signs or symptoms. There were four adults and four children; all have been successfully treated with enzyme replacement therapy. Routine means of monitoring pulmonary status including clinical assessment, chest X-ray, pulmonary function tests, and high-resolution CT (HRCT) were used. Enzyme treatment resulted in decreased hepatosplenomegaly, improved haematological parameters, and increased well-being; There was decreased clubbing and decreased dyspnoea in some of the patients, although on radiology, lung pathology had not normalized. All four children showed improved respiratory compliance, with significant improvement of the radiological findings in one and unchanged disease in the others. Two adults showed improvement in oxygen saturation but worsening of pulmonary hypertension. On chest X-ray, both had increased interstitial markings; one had gradual progression of pulmonary artery accentuation and fine interstitial stable pattern on HRCT. The other two adults had no change in lung function or on chest X-ray, but on HRCT there was apparent improvement in one patient. There is great heterogeneity in presentation and response to enzyme therapy in patients with Gaucher's disease and symptomatic lung involvement. Clinically, some benefited significantly from enzyme therapy, but in contrast to the dramatic reduction in organomegaly, there was no normalization in pulmonary function or lung architecture.

Pulmonary Involvement in Adult Patients with Inborn Errors of Metabolism

“…Type 1 GD patients respond well to ERT [30] with improvement of hepatosplenomegaly and hematological parameters as well as increased well-being [31] . Nevertheless, there is a wide heterogeneity in the response of pulmonary manifestations to ERT [30] . Schiffmann et al [32] reported that miglustat in combination with ERT may have positive effects by improving pulmonary function.…”

Lungenbeteiligung bei erwachsenen Patienten mit angeborenen Stoffwechselerkrankungen

“…Zwei therapeutische Ansätze stehen zur Verfügung: 1. eine ERT mit rekombinanter humaner Glucocerebrosidase oder 2. die Substratreduktionstherapie mit Miglustat. Patienten mit M. Gaucher Typ 1 sprechen gut auf eine ERT [30] an und zeigen eine Besserung der Hepatosplenomegalie, der hämatologischen Parameter und des Wohlbefindens [31]. Die pulmonalen Manifestationen sprechen allerdings sehr unterschiedlich auf eine ERT an [30].…”

“…Patienten mit M. Gaucher Typ 1 sprechen gut auf eine ERT [30] an und zeigen eine Besserung der Hepatosplenomegalie, der hämatologischen Parameter und des Wohlbefindens [31]. Die pulmonalen Manifestationen sprechen allerdings sehr unterschiedlich auf eine ERT an [30]. Schiffmann et al [32] berichteten, dass die Kombinationstherapie von Miglustat und ERT positive Effekte haben kann, da sie die Lungenfunktion verbessert.…”

Hampered Vitamin B12 Metabolism in Gaucher Disease?

“…GBA1 mutations may alter GCase stability and/or impair its catalytic function. 37,38 The identification of disease-causing mutations in GBA1 may be challenging due to the GBAP. The most accurate method for mutation analysis in GD is full-gene sequencing of GBA1.…”