| Domain | CESD / later-onset LAL-D core fact | Evidence |
|---|---|---|
| Preferred disease name | Cholesteryl ester storage disease (historical term); currently considered the later-onset form of lysosomal acid lipase deficiency (LAL-D) | (pqac-00000010, pqac-00000012) |
| Synonyms / alternative names | CESD; cholesteryl-ester storage disease; later-onset LAL-D; childhood/adult-onset LAL-D | (pqac-00000010, pqac-00000012, pqac-00000016) |
| MONDO ID | MONDO:0019149 | (pqac-00000000) |
| OMIM | LAL-D / shared disease entry: OMIM 278000 | (pqac-00000010, pqac-00000012) |
| Causal gene | **LIPA** (lipase A, lysosomal acid type); OMIM gene entry noted as *LIPA* MIM *613497* | (pqac-00000010, pqac-00000011) |
| Inheritance | Autosomal recessive; caused by biallelic pathogenic variants in **LIPA** | (pqac-00000010, pqac-00000011, pqac-00000016) |
| Enzyme defect / residual activity | Deficiency of lysosomal acid lipase (LAL); later-onset disease typically retains about **1%–12%** of normal LAL activity, with older review language noting up to **~10%** residual activity | (pqac-00000011, pqac-00000012, pqac-00000013) |
| Key pathobiology | Impaired intralysosomal hydrolysis of cholesteryl esters and triglycerides from LDL causes lipid accumulation, especially in liver and mononuclear phagocyte system, with downstream dyslipidemia and chronic liver injury | (pqac-00000011, pqac-00000012) |
| Key diagnostic test | Dried blood spot (DBS) LAL enzyme assay is described as the quickest, most reliable, and gold-standard screening/confirmatory approach in suspected disease | (pqac-00000010, pqac-00000013, pqac-00000016) |
| Diagnostic thresholds | DBS **<5%** mean normal LAL activity: diagnostic for LAL-D; **5%–10%**: repeat testing plus molecular sequencing; **>10%**: reported as not affected | (pqac-00000013) |
| Genetic confirmation | Diagnosis can also be confirmed by identification of biallelic pathogenic **LIPA** variants | (pqac-00000011) |
| Epidemiology estimates | Later-onset prevalence reported around **1 per 300,000** individuals; older overall LAL-D estimates ranged from **1:40,000 to 1:300,000**; predicted prevalence may exceed diagnosed prevalence because of underdiagnosis/misdiagnosis | (pqac-00000011, pqac-00000013, pqac-00000017) |
| Common variant | **c.894G>A** exon 8 splice junction mutation (**E8SJM**) is the most common reported variant | (pqac-00000013) |
| Common variant contribution | E8SJM accounts for about **50% of reported cases** and is associated with residual activity (~**2%–4%**), explaining its association with later-onset disease | (pqac-00000013) |
| Variant population frequency / inferred prevalence | E8SJM allele frequency is approximately **1:300** in Caucasian and Hispanic populations, corresponding to a predicted later-onset prevalence of about **1:130,000** in those groups | (pqac-00000013) |
| Primary organs / systems affected | Liver, spleen, intestine/gastrointestinal tract, adrenal glands, lymph nodes, bone marrow, macrophages; clinical burden is dominated by chronic liver injury and dyslipidemia in later-onset disease | (pqac-00000013, pqac-00000016) |
| Common clinical clues in later-onset disease | Elevated aminotransferases, dyslipidemia with low HDL, hepatosplenomegaly, occasional GI disturbances; may progress to fibrosis/cirrhosis and premature cardiovascular disease | (pqac-00000011, pqac-00000013, pqac-00000017) |
| Approved disease-specific therapy | **Sebelipase alfa** enzyme replacement therapy (ERT); authorized in the EU since 2015 and described as the only established/approved specific therapy in gathered evidence | (pqac-00000012, pqac-00000015, pqac-00000016) |
| Pivotal sebelipase alfa trials | Adult CESD phase 1/2 clinical-effect study: **Hepatology 2013** (Deegan/Balwani et al.); phase 3 **ARISE**, **N Engl J Med 2015**; 52-week study **J Hepatol 2014**; long-term extension **Liver Int 2020**; final ARISE results **J Hepatol 2022** | (pqac-00000008, pqac-00000015) |


*Table: This table summarizes identifiers, genetics, diagnostics, epidemiology, major organs involved, and pivotal therapy evidence for cholesteryl ester storage disease (later-onset LAL-D). It is designed as a compact reference artifact for knowledge-base population and citation tracking.*