Cholesteryl ester storage disease : Fatal outcome without causal therapy in a female patient with the preventable sequelae of progressive liver disease after many years of mild symptoms

Patient: Female, 13 Final Diagnosis: Multiorgan failure as a sequelae of advanced liver disease Symptoms: A lysosomal enzyme defect • abnormal bilirubin level • abnormal lipid profile • cardiovascular complications • Child-Pugh A/B • cholestasis and/or gallbladder dysfunction • chronic and florid fibroplastic cholecystitis • frequent diarrhoea • greatly elevated hepatic content of cholesteryl esters • hepatic fibrosis • hepatomegaly • hepatosplenomegaly with thrombocytopenia • increasing jaundice • increasing transaminases • Lab-MELD 14 cirrhosis • malabsorption • oesophageal varices (Grade III) • orange-yellow liver • pressure in the right epigastrium • steatorrhoea • symptomatic gallstones • Vitamin D deficiency Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Cholesteryl ester storage disease (CESD), also known as lysosomal acid lipase deficiency (LAL-D), is a rare autosomal-recessive inheritable lysosomal storage disease. Since 2015, a causal treatment with sebelipase alfa, which replaces the missing LAL enzyme, has been approved. We report a fatal course of LAL-D in a female patient. Case Report: In 1979, CESD was first diagnosed in a 13-year-old female with marked hepatomegaly. At that time, no specific treatment for CESD was available and the spontaneous course of the disease had to be awaited. In 2013, a laparoscopic cholecystectomy for symptomatic gallstones was performed. The patient’s CESD had caused a Child-Pugh A/B and Lab-MELD 14 cirrhosis with esophageal varices (grade III), a solitary fundal varix, as well as hepatosplenomegaly with thrombocytopenia. In 2016, the patient was admitted with compensated cirrhosis and splenomegaly for a ligature of esophageal varices which was complicated by vomiting of blood followed by severe coagulopathy and hemorrhagic shock. The dried blood test showed reduced acid lipase (0.03 nmol/spot*3 hours; reference range 0.2–2) and beta-galactosidase (0.08 nmol/spot*21 hours; reference range 0.5–3.2). Then 15 days after the esophageal varices bleed, the patient died due to multiorgan failure as a sequelae of advanced liver disease. Conclusions: LAL-D should be included in the differential diagnosis of lipid metabolism disorder, hepatomegaly, and non-alcoholic fatty liver disease with fibrosis or cirrhosis. Causal treatment with sebelipase alfa should be introduced even in patients who have LAL-D and many years of clinically mild symptoms of this disease to prevent the serious sequelae of cirrhosis or cardiovascular complications.