Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesteryl ester storage disease (CESD, OMIM #278000) and Wolman disease (OMIM #278000) are autosomal recessive lysosomal storage disorders caused by a deficient activity of lysosomal acid lipase (cholesteryl ester hydrolase, LAL). Human lysosomal acid lipase is essential for the metabolism of cholesteryl esters and triglycerides. In Wolman disease, LAL activity is usually absent, whereas CESD usually presents some residual LAL activity. In infants, poor weight gain, massive hepatosplenomegaly, calcified adrenal glands (present about 2/3 of the time), vomiting, diarrhea and failure to thrive are indicative of Wolman disease. The clinical picture is more variable in CESD. Hepatomegaly and/or elevation of liver transaminases are almost always present. Hepatic steatosis often leads to fibrosis and cirrhosis. Other signs often include splenomegaly, high total cholesterol and LDL-cholesterol, elevated triglycerides, and low HDL-cholesterol. The diagnosis of LAL deficiency requires clinical experience and specialized laboratory tests. The diagnosis is based on finding deficient activity of acid lipase and/or molecular tests. Pilot screening projects using dried blood spot testing in 1) children with atypical fatty liver disease in the absence of overweight, 2) patients with dyslipidaemia and presence of hepatomegaly and/or elevated transaminases, 3) newborns/neonates with hepatomegaly and abdominal distension/failure to thrive/elevated transaminases are currently underway. Early diagnosis is particularly important for the enzyme replacement therapy. Human trials with recombinant LAL are currently ongoing, raising the prospect for specific correction of LAL deficiency in this progressive and often debilitating disorder.
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PMID:Lysosomal acid lipase deficiency: wolman disease and cholesteryl ester storage disease. 2479

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.
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PMID: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. 2977 83

Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease that may present from infancy to late adulthood depending on residual enzyme activity. While the severe form manifests as a rapidly progressive disease with near universal mortality within the first 6 months of life, milder forms frequently go undiagnosed for prolonged periods and typically present with progressive fatty liver disease, enlarged spleen, atherogenic dyslipidemia and premature atherosclerosis. The adult variant of LAL-D is typically diagnosed late or even overlooked due to the unspecific nature of the presenting symptoms, which are similar to common changes observed in the context of the metabolic syndrome. This review is aimed at delineating clinically useful scenarios in which pediatric or adult medicine clinicians should be aware of LAL-D as a differential diagnosis for selected patients. This is particularly relevant as a potentially life-saving enzyme replacement therapy has become available and the diagnosis can easily be ruled out or confirmed using a dried blood spot test.
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PMID:Lysosomal acid lipase deficiency - early diagnosis is the key. 3121 32