To estimate the ICER/ICUR of ultra-orphan drugs marketed for LSDs (alglucosidase alfa [Myozyme®], agalsidase alfa [Replagal®], algasidase beta [Fabrazyme®], alglucerase, imiglucerase, velaglucerase alfa and mercaptamine [Procysbi®]) and for paroxysmal nocturnal haemoglobinuria (eculizumab [Soliris®]), these drugs have been compared to standard medical care, while ultra-orphan drugs for PAH (sildenafil [Revatio®], iloprost [Ventavis®], bosentan [Tracleer®] and ambrisentan [Volibris®]) have been compared with each other. This evidence concerns the gene GLA and pulmonary arterial hypertension.