Research Article Details
| Article ID: | A27083 |
| PMID: | 19214773 |
| Source: | J Inherit Metab Dis |
| Title: | Combined hyperlipidaemia as a presenting sign of cholesteryl ester storage disease. |
| Abstract: | Lysosomal acid lipase (LAL) deficiency results in Wolman disease and cholesteryl ester storage disease (CESD), a more benign form. CESD is a recessive disorder characterized by hypercholesterolaemia, hypertriglyceridaemia, low blood HDL and variable phenotype, while hepatomegaly is usually evident during childhood or adolescence. An 11-year-old girl was referred to our department for combined hyperlipidaemia (total cholesterol 323, triglycerides 259 mg/dl). All family members had normal lipid profile and liver function tests. At 8 years she was admitted for acute Epstein-Barr virus infection, with hepatosplenomegaly and elevation of liver enzymes. Liver-spleen enlargement resolved, but serum alanine aminotransferase and aspartate aminotransferase were persistently twice the upper limits, with other liver function tests within the normal range. Ultrasonography showed normal liver and spleen size and minimal hepatic steatosis. Infectious, autoimmune and metabolic causes of elevated liver enzymes were ruled out, including glycogen storage disease. Dysbetalipoproteinaemia was also ruled out (ApoE phenotype: E3E3). In the following 2 years the girl was symptom-free, BMI was at the 50th-75th centile for age and lipid profile was unchanged despite a low-fat diet. At 13 years of age, low acid lipase activity was demonstrated in leukocytes (10 nmol/h/ per mg protein, normal 140-380) and cultured skin fibroblasts (181 nmol/h per mg protein, normal 1100-2400), leading to diagnosis of CESD. CESD usually progresses to hepatic fibrosis, with high risk of premature atherosclerosis. CESD prevalence may be underestimated in the general population. The diagnosis may be considered in all subjects with atypical combined hyperlipidaemia (usually dominant in transmission or related to metabolic syndrome) and atypical 'fatty liver disease', in the absence of overweight. |
| DOI: | 10.1007/s10545-008-1027-2 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |