| Topic | Key facts | Ontology/identifier suggestions | Key citations |
|---|---|---|---|
| Disease definition | Rare autosomal recessive neutral lipid storage disorder with ichthyosis; characterized by intracellular triacylglycerol accumulation in multiple tissues and non-bullous congenital ichthyosiform erythroderma/ichthyosis. Common alternate names: Chanarin–Dorfman syndrome (CDS), Dorfman–Chanarin syndrome, neutral lipid storage disease with ichthyosis (NLSDI). (pqac-00000009, pqac-00000011, pqac-00000016) | OMIM/MIM: **275630**; ICD-10: **E75.5**; MONDO: not found in retrieved evidence; MeSH: not found in retrieved evidence; Orphanet: placeholder only in retrieved evidence | Demerjian 2006 DOI:10.1038/sj.jid.5700332 URL:https://doi.org/10.1038/sj.jid.5700332; Redaelli 2010 DOI:10.1186/1750-1172-5-33 URL:https://doi.org/10.1186/1750-1172-5-33; Fischer 2023 DOI:10.1515/medgen-2023-2006 URL:https://doi.org/10.1515/medgen-2023-2006 (pqac-00000009, pqac-00000011, pqac-00000016) |
| Causal gene and inheritance | Caused by biallelic **ABHD5** variants; ABHD5 encodes **CGI-58**, a co-activator of **ATGL/PNPLA2**. Loss of ABHD5 impairs triglyceride hydrolysis, causing lipid-droplet accumulation. Autosomal recessive inheritance is consistently reported. ABHD5 gene MIM **604780** noted in retrieved evidence. (pqac-00000003, pqac-00000011, pqac-00000016, pqac-00000022) | Gene: **ABHD5/CGI-58**; OMIM gene: **604780**; Disease OMIM: **275630** | Elsayed 2023 DOI:10.1016/j.gendis.2022.08.005 URL:https://doi.org/10.1016/j.gendis.2022.08.005; Redaelli 2010 DOI:10.1186/1750-1172-5-33 URL:https://doi.org/10.1186/1750-1172-5-33; Schratter 2022 DOI:10.3390/metabo12111015 URL:https://doi.org/10.3390/metabo12111015 (pqac-00000003, pqac-00000011, pqac-00000022) |
| Epidemiology and reported case counts | Extremely rare. Reported counts have increased over time in the literature surveyed: ~**55 cases** by 2010; **128 reported patients** with **85 molecularly confirmed** by 2021 in one review; **151 reported patients worldwide** by 2021; fewer than **120 cases** stated in one 2023 case report/review, reflecting source-to-source update differences. Largest single-country cohort in retrieved evidence: **40 Turkish cases**. (pqac-00000011, pqac-00000008, pqac-00000010, pqac-00000007) | Rare disease; prevalence not provided in retrieved evidence | Redaelli 2010 DOI:10.1186/1750-1172-5-33 URL:https://doi.org/10.1186/1750-1172-5-33; Waheed 2021 DOI:10.1186/s43042-021-00189-2 URL:https://doi.org/10.1186/s43042-021-00189-2; Tavian 2021 DOI:10.4081/ejtm.2021.9796 URL:https://doi.org/10.4081/ejtm.2021.9796; Mangukiya 2023 DOI:10.7759/cureus.43889 URL:https://doi.org/10.7759/cureus.43889 (pqac-00000011, pqac-00000008, pqac-00000010, pqac-00000007) |
| Core clinical phenotype | Skin involvement is the dominant and often universal feature: congenital ichthyosis/NCIE; some patients are born as collodion babies; pruritus may be intense. Multisystem features include hepatomegaly/steatosis, myopathy or muscle weakness, hearing loss, cataracts/other ocular findings, CNS involvement, and occasional cardiomyopathy. (pqac-00000016, pqac-00000007, pqac-00000003, pqac-00000001) | Suggested phenotype labels: congenital ichthyosis; hepatomegaly; hepatic steatosis; myopathy; cataract; sensorineural hearing loss | Fischer 2023 DOI:10.1515/medgen-2023-2006 URL:https://doi.org/10.1515/medgen-2023-2006; Mangukiya 2023 DOI:10.7759/cureus.43889 URL:https://doi.org/10.7759/cureus.43889; Elsayed 2023 DOI:10.1016/j.gendis.2022.08.005 URL:https://doi.org/10.1016/j.gendis.2022.08.005; El-Ammari 2024 DOI:10.7241/ourd.20244.22 URL:https://doi.org/10.7241/ourd.20244.22 (pqac-00000016, pqac-00000007, pqac-00000003, pqac-00000001) |
| Phenotype frequencies/statistics | Retrieved reviews/case summaries report: **hepatomegaly 60%**, **myopathy 59%**, **ectropion 29%**, **cataract 22%**, **deafness 17%**, **splenomegaly 13%**; liver involvement reported in **>80%** in one 2023 paper and about **85%** in a 2021 cohort review; neurological symptoms in **~30%**; muscle involvement **40%** in one series. In genotype-stratified data, severe/truncating ABHD5 variants were associated with **36% myopathy** and **67.5% CK elevation** vs **15%** and **30%** for missense variants. (pqac-00000000, pqac-00000003, pqac-00000014) | Frequency data from aggregated literature, not formal registry prevalence | Mangukiya 2023 DOI:10.7759/cureus.43889 URL:https://doi.org/10.7759/cureus.43889; Elsayed 2023 DOI:10.1016/j.gendis.2022.08.005 URL:https://doi.org/10.1016/j.gendis.2022.08.005; Tavian 2021 DOI:10.4081/ejtm.2021.9796 URL:https://doi.org/10.4081/ejtm.2021.9796 (pqac-00000000, pqac-00000003, pqac-00000014) |
| Diagnostic hallmark | **Jordans’ anomaly**—lipid vacuoles in granulocytes/leukocytes on peripheral blood smear—is the classic, simple diagnostic hallmark; reported as demonstrable by May–Grünwald–Giemsa/peripheral smear and considered characteristic/pathognomonic in multiple sources. Tissue biopsies can show neutral lipid droplets in skin, liver, muscle, kidney tubular epithelium, and other cells. (pqac-00000000, pqac-00000008, pqac-00000016, pqac-00000005) | Suggested diagnostic label: Jordans’ anomaly; peripheral smear for lipid vacuoles | Waheed 2021 DOI:10.1186/s43042-021-00189-2 URL:https://doi.org/10.1186/s43042-021-00189-2; Mangukiya 2023 DOI:10.7759/cureus.43889 URL:https://doi.org/10.7759/cureus.43889; Fischer 2023 DOI:10.1515/medgen-2023-2006 URL:https://doi.org/10.1515/medgen-2023-2006; Agrebi 2023 DOI:10.4103/ijn.ijn_203_22 URL:https://doi.org/10.4103/ijn.ijn_203_22 (pqac-00000000, pqac-00000008, pqac-00000016, pqac-00000005) |
| Laboratory, imaging, pathology | Serum lipids may be normal, but liver enzymes and CK/CPK are often elevated; muscle enzymes elevated in **>50%** in one 2024 report. Imaging/pathology may show fatty liver, hepatomegaly, fibrosis/cirrhosis; kidney biopsy can reveal mesangial proliferative glomerulonephritis with extensive tubular lipid vacuoles in rare renal involvement. Skin barrier studies showed abnormal basal TEWL and SC integrity with lipid micro-inclusions in lamellar bodies. (pqac-00000011, pqac-00000001, pqac-00000005, pqac-00000009) | Suggested workup: AST/ALT/GGT, CK/CPK, liver ultrasound/FibroScan, biopsy if indicated | Redaelli 2010 DOI:10.1186/1750-1172-5-33 URL:https://doi.org/10.1186/1750-1172-5-33; El-Ammari 2024 DOI:10.7241/ourd.20244.22 URL:https://doi.org/10.7241/ourd.20244.22; Agrebi 2023 DOI:10.4103/ijn.ijn_203_22 URL:https://doi.org/10.4103/ijn.ijn_203_22; Demerjian 2006 DOI:10.1038/sj.jid.5700332 URL:https://doi.org/10.1038/sj.jid.5700332 (pqac-00000011, pqac-00000001, pqac-00000005, pqac-00000009) |
| Variant spectrum | Retrieved evidence notes substantial allelic heterogeneity. Counts vary by publication date: **45 different ABHD5 mutations** reported in one 2023 paper; **at least 78 mutations** in a 2023 review/case report; many mutation classes reported, including nonsense, missense, frameshift, splice-site, large deletions, and promoter/complex rearrangements. **77%** of variants were truncating in one 2023 source. Recurrent **N209\*** is especially common, accounting for **52% (21/40)** of Turkish cases and **16% (24/151)** of all reported cases in one 2021 review. (pqac-00000003, pqac-00000000, pqac-00000010, pqac-00000011) | Variant classes: truncating, missense, frameshift, splice-site, large deletion | Elsayed 2023 DOI:10.1016/j.gendis.2022.08.005 URL:https://doi.org/10.1016/j.gendis.2022.08.005; Mangukiya 2023 DOI:10.7759/cureus.43889 URL:https://doi.org/10.7759/cureus.43889; Tavian 2021 DOI:10.4081/ejtm.2021.9796 URL:https://doi.org/10.4081/ejtm.2021.9796; Redaelli 2010 DOI:10.1186/1750-1172-5-33 URL:https://doi.org/10.1186/1750-1172-5-33 (pqac-00000003, pqac-00000000, pqac-00000010, pqac-00000011) |
| Mechanism / pathophysiology | ABHD5/CGI-58 normally activates ATGL-mediated lipolysis and also interfaces with epidermal lipid metabolism; deficiency causes TAG accumulation in cytoplasmic lipid droplets across tissues and contributes to skin-barrier dysfunction. J Invest Dermatol data linked epidermal disease to lamellar-body lipid micro-inclusions, non-lamellar extracellular lipid phases, abnormal barrier function, and increased transepidermal water loss. (pqac-00000009, pqac-00000016, pqac-00000022) | Mechanistic axis: ABHD5/CGI-58 → ATGL/PNPLA2 activation → triglyceride hydrolysis | Demerjian 2006 DOI:10.1038/sj.jid.5700332 URL:https://doi.org/10.1038/sj.jid.5700332; Fischer 2023 DOI:10.1515/medgen-2023-2006 URL:https://doi.org/10.1515/medgen-2023-2006; Schratter 2022 DOI:10.3390/metabo12111015 URL:https://doi.org/10.3390/metabo12111015 (pqac-00000009, pqac-00000016, pqac-00000022) |
| Notable atypical/less common manifestations | Rare or less common manifestations in retrieved evidence include renal involvement/nephrotic syndrome, thyroid dysfunction in adults from a founder-mutation series, possible cardiomyopathy, cerebellar/white-matter abnormalities, developmental delay, and severe CNS malformations in isolated case reports. (pqac-00000005, pqac-00000006) | Multisystem disease; no separate identifier in retrieved evidence | Agrebi 2023 DOI:10.4103/ijn.ijn_203_22 URL:https://doi.org/10.4103/ijn.ijn_203_22; Elsayed 2023 DOI:10.1016/j.gendis.2022.08.005 URL:https://doi.org/10.1016/j.gendis.2022.08.005 (pqac-00000005, pqac-00000006) |
| Current management | No disease-specific approved therapy was identified in retrieved evidence. Management is supportive/multidisciplinary: low-fat or low-long-chain-fat diet, **medium-chain triglyceride (MCT) oil** supplementation, vitamin E, ursodeoxycholic acid, topical emollients, and selective use of **acitretin** for ichthyosis with monitoring. One case summary reported normalization of enzymes/loss of inclusions and **50% liver-size reduction after 1 year** on dietary/supportive therapy. Expert reviews emphasize early diagnosis for management of metabolic/cardiac complications and genetic counseling. (pqac-00000000, pqac-00000001, pqac-00000008, pqac-00000019, pqac-00000016) | Supportive care; dietary therapy; dermatologic treatment | Mangukiya 2023 DOI:10.7759/cureus.43889 URL:https://doi.org/10.7759/cureus.43889; El-Ammari 2024 DOI:10.7241/ourd.20244.22 URL:https://doi.org/10.7241/ourd.20244.22; Waheed 2021 DOI:10.1186/s43042-021-00189-2 URL:https://doi.org/10.1186/s43042-021-00189-2; Tavian 2021 DOI:10.4081/ejtm.2021.9796 URL:https://doi.org/10.4081/ejtm.2021.9796; Fischer 2023 DOI:10.1515/medgen-2023-2006 URL:https://doi.org/10.1515/medgen-2023-2006 (pqac-00000000, pqac-00000001, pqac-00000008, pqac-00000019, pqac-00000016) |
| Real-world implementations / research infrastructure | An international observational registry for **NLSD/TGCV and related diseases** is recruiting (**NCT02918032**, target enrollment ~**120**), capturing NLSDI/CDS and NLSDM with longitudinal outcomes including survival, CK, liver tests, thyroid tests, imaging, function, and biopsy data. Interventional studies retrieved are focused mainly on **NLSDM/PNPLA2** rather than ABHD5-NLSDI: **bezafibrate** Phase 4 (**NCT01527318**) and **CNT-02 medium-chain fatty acid capsules** (**NCT02830763**, terminated). (pqac-00000020, pqac-00000021, pqac-00000023, pqac-00000024, pqac-00000025) | ClinicalTrials.gov: **NCT02918032**, **NCT01527318**, **NCT02830763** | ClinicalTrials.gov NCT02918032 URL:https://clinicaltrials.gov/study/NCT02918032; NCT01527318 URL:https://clinicaltrials.gov/study/NCT01527318; NCT02830763 URL:https://clinicaltrials.gov/study/NCT02830763 (pqac-00000020, pqac-00000021, pqac-00000023, pqac-00000024, pqac-00000025) |


*Table: This table compiles the core identifiers, genetics, phenotypes, diagnostics, pathophysiology, management, and registry/trial landscape for Dorfman–Chanarin disease/Chanarin–Dorfman syndrome (NLSDI) using only the retrieved evidence. It is designed as a compact reference for building a disease knowledge base entry.*