Skip to content
How It Works
Explore
Ask a Question Resources Pricing
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Sign Up
PubMed This is a summary of 22 peer-reviewed journal articles Updated
Dermatology

The Biology and Diagnosis of NLSDI/Chanarin-Dorfman Syndrome

At a Glance

NLSDI (Chanarin-Dorfman syndrome) is a rare inherited disorder caused by disease-causing changes in both copies of the ABHD5 gene. Fat droplets in white blood cells can support the diagnosis, but genetic testing confirms it; liver, muscle, eye, and hearing problems may also occur.

The journey to a diagnosis of Neutral Lipid Storage Disease with Ichthyosis (NLSDI) often involves peeling back layers of complex biology. While the skin symptoms are the most visible, they are the outward sign of a unique metabolic process occurring deep within your cells. Understanding the biology of NLSDI can help you and your medical team move from treating symptoms to managing the condition’s underlying cause.

The Biology of Lipid Storage

Inside almost every cell in your body, fats are stored in tiny, round compartments called lipid droplets [1]. In a healthy body, these droplets are regularly broken down to provide energy or build new structures. This process requires a specific “key” to unlock the droplets.

  • The Key (ABHD5): NLSDI is caused by mutations in the ABHD5 gene (also known as CGI-58). This gene produces a protein that acts as a co-activator—essentially a “helper”—for an enzyme called ATGL [2][3].
  • The Breakdown: When the ABHD5 protein is working correctly, it activates ATGL, which then breaks down triacylglycerols (a type of fat) into fuel for the cell [1].
  • The Accumulation: In NLSDI, the ABHD5 helper protein is missing or broken. Because the “key” doesn’t work effectively, the cell’s ability to break down stored fats is severely impaired. As a result, these fats build up and form large, abnormal droplets inside cells throughout the body [3].

Why the Skin is Affected

You may wonder why a fat-storage problem causes a skin condition like ichthyosis (dry, scaly skin). Research has found that ABHD5 has a second, crucial job specifically in the skin.

In the outer layer of the skin (the epidermis), ABHD5 helps another enzyme produce omega-O-acylceramides [4][5]. These specialized fats are the “mortar” that holds your skin cells together to form a waterproof barrier [6]. When ABHD5 function is disrupted, the skin cannot produce this protective seal, leading to the redness and fine white scales of congenital nonbullous ichthyosiform erythroderma [7][8].

Recognizing the Full Spectrum of Symptoms

While the skin is involved from birth, NLSDI is a multisystem condition. The severity of these symptoms can vary widely between individuals [9]:

  • Liver Involvement: Fat buildup in the liver (steatosis) is common. Over time, this can lead to an enlarged liver (hepatomegaly) or even more serious scarring known as cirrhosis [10][11].
  • Muscles: Some patients experience myopathy (muscle weakness) or elevated levels of creatine kinase, an enzyme that indicates muscle stress [9][12].
  • Senses: Fat accumulation can also affect the eyes, leading to cataracts, and the ears, causing sensorineural hearing loss [13][14].
  • Heart: While significant cardiac involvement (cardiomyopathy) is much less characteristic in NLSDI than in related disorders, it has been reported in rare cases and may warrant symptom-driven assessment by a cardiologist.

Differentiating NLSDI from NLSDM

It is important to distinguish this condition from Neutral Lipid Storage Disease with Myopathy (NLSDM). While they sound similar, they are caused by different genetic mutations. NLSDM involves the PNPLA2 gene and characteristically does not include the skin scaling seen in NLSDI [15]. NLSDM also carries a much higher risk of severe heart issues (cardiomyopathy), which is less frequent in NLSDI [16].

The Path to Diagnosis

Because NLSDI is so rare, it is frequently misdiagnosed as other skin conditions, such as pityriasis rubra pilaris [8][17]. Doctors use two primary tools to evaluate and confirm a diagnosis:

  1. Jordan’s Anomaly: This is often the first “clue.” When a technician looks at a drop of your blood under a microscope (a peripheral blood smear), they look for Jordan’s bodies—small, clear bubbles of fat trapped inside white blood cells called granulocytes [18][19]. Finding these “lipid vacuoles” is a supportive hallmark sign of a neutral lipid storage disorder, though it may not be present in every single patient or may require expert interpretation [20].
  2. Genetic Testing: The definitive confirmation requires molecular testing of the ABHD5 gene [21]. Specifically, the laboratory must find biallelic pathogenic or likely pathogenic variants (meaning a disease-causing mutation was inherited from both parents). A “variant of uncertain significance” does not establish the diagnosis on its own, and a clinical correlation by a geneticist is necessary [22].

Common questions in this guide

What causes NLSDI or Chanarin-Dorfman syndrome?
NLSDI results from disease-causing changes in both copies of the ABHD5 gene, usually inherited one from each parent. Without working ABHD5, cells have trouble breaking down stored fat, so fat droplets accumulate and the skin barrier is also affected.
What is Jordan's anomaly, and what does it mean?
Jordan's anomaly means that fat-filled spaces are seen inside certain white blood cells on a peripheral blood smear. It is a helpful clue for a neutral lipid storage disorder, but it may be absent or require an experienced laboratory reviewer, so it does not replace genetic testing.
What genetic test confirms NLSDI?
Confirmation generally requires genetic testing that finds pathogenic or likely pathogenic changes in both copies of ABHD5. A variant of uncertain significance alone does not establish the diagnosis, so results should be interpreted alongside symptoms and a geneticist's assessment.
Which organs can NLSDI affect besides the skin?
NLSDI can cause fat buildup in the liver and may be associated with an enlarged liver or scarring, as well as muscle weakness or elevated muscle enzymes. Cataracts and sensorineural hearing loss can occur, while heart muscle disease is uncommon but has been reported.
How is NLSDI different from NLSDM?
NLSDI is linked to ABHD5 changes and includes congenital ichthyosis, or dry, scaly skin. NLSDM is linked to PNPLA2 changes, usually lacks the skin scaling, and has a higher risk of serious heart muscle disease.
What follow-up tests might be useful after an NLSDI diagnosis?
Clinicians may follow liver enzymes and creatine kinase and use liver imaging, such as ultrasound or elastography, to assess organ involvement. Hearing and vision checks may help detect hearing loss or cataracts, and heart testing is guided by symptoms and clinical findings.
Why is NLSDI sometimes mistaken for another skin condition?
Because the skin changes can resemble other disorders, NLSDI may initially be labeled as pityriasis rubra pilaris or another ichthyosis. The combination of multisystem findings, blood-smear findings, and ABHD5 genetic testing can help clarify the diagnosis.

Get notified when new evidence is published on Neutral lipid storage disease with ichthyosis.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References

References (22)
  1. 1

    Structure of a CGI-58 motif provides the molecular basis of lipid droplet anchoring.

    Boeszoermenyi A, Nagy HM, Arthanari H, et al.

    The Journal of biological chemistry 2015; (290(44)):26361-72 doi:10.1074/jbc.M115.682203.

    PMID: 26350461
  2. 2

    Critical roles for α/β hydrolase domain 5 (ABHD5)/comparative gene identification-58 (CGI-58) at the lipid droplet interface and beyond.

    Brown AL, Mark Brown J

    Biochimica et biophysica acta. Molecular and cell biology of lipids 2017; (1862(10 Pt B)):1233-1241 doi:10.1016/j.bbalip.2017.07.016.

    PMID: 28827091
  3. 3

    CGI-58: Versatile Regulator of Intracellular Lipid Droplet Homeostasis.

    Yu L, Li Y, Grisé A, Wang H

    Advances in experimental medicine and biology 2020; (1276()):197-222 doi:10.1007/978-981-15-6082-8_13.

    PMID: 32705602
  4. 4

    ABHD5 stimulates PNPLA1-mediated ω-O-acylceramide biosynthesis essential for a functional skin permeability barrier.

    Kien B, Grond S, Haemmerle G, et al.

    Journal of lipid research 2018; (59(12)):2360-2367 doi:10.1194/jlr.M089771.

    PMID: 30361410
  5. 5

    Defective targeting of PNPLA1 to lipid droplets causes ichthyosis in ABHD5-syndromic epidermal differentiation disorder.

    Schratter M, Holubek D, Koeffler L, et al.

    Journal of lipid research 2025; (66(9)):100875 doi:10.1016/j.jlr.2025.100875.

    PMID: 40818613
  6. 6

    PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis.

    Hirabayashi T, Anjo T, Kaneko A, et al.

    Nature communications 2017; (8()):14609 doi:10.1038/ncomms14609.

    PMID: 28248300
  7. 7

    Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation.

    Grond S, Radner FPW, Eichmann TO, et al.

    The Journal of investigative dermatology 2017; (137(2)):403-413 doi:10.1016/j.jid.2016.09.025.

    PMID: 27725204
  8. 8

    A novel mutation of ABHD5 gene in a Chanarin Dorfman patient with unusual dermatological findings.

    Eskiocak AH, Missaglia S, Moro L, et al.

    Lipids in health and disease 2019; (18(1)):232 doi:10.1186/s12944-019-1181-6.

    PMID: 31883530
  9. 9

    Recurrent N209* ABHD5 mutation in two unreported families with Chanarin Dorfman Syndrome.

    Tavian D, Durdu M, Angelini C, et al.

    European journal of translational myology 2021; (31(2)) doi:10.4081/ejtm.2021.9796.

    PMID: 33985321
  10. 10

    Chanarin-Dorfman Syndrome: A comprehensive review.

    Cakmak E, Bagci G

    Liver international : official journal of the International Association for the Study of the Liver 2021; (41(5)):905-914 doi:10.1111/liv.14794.

    PMID: 33455044
  11. 11

    Dorfman-Chanarin Syndrome: A Rare Cause of Metabolic Associated Fatty Liver Disease Related to Homozygosity of the Nonsense Mutation c.934C>T (p.R312*).

    Quelhas da Costa R, Laranjeira F, Duarte Ribeiro I, et al.

    GE Portuguese journal of gastroenterology 2022; (29(4)):284-290 doi:10.1159/000517103.

    PMID: 35979251
  12. 12

    Long-term neuromuscular, cardiac and liver outcomes in an adult man affected with Chanarin-Dorfman syndrome.

    Noman K, Tridimas A, Lilleker JB, et al.

    Molecular genetics and metabolism reports 2025; (45()):101265 doi:10.1016/j.ymgmr.2025.101265.

    PMID: 41127218
  13. 13

    Thyroid involvement in Chanarin-Dorfman syndrome in adults in the largest series of patients carrying the same founder mutation in ABHD5 gene.

    Louhichi N, Bahloul E, Marrakchi S, et al.

    Orphanet journal of rare diseases 2019; (14(1)):112 doi:10.1186/s13023-019-1095-4.

    PMID: 31118107
  14. 14

    Chanarin-Dorfman syndrome.

    Kalyon S, Gökden Y, Demirel N, et al.

    The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 2019; (30(1)):105-108 doi:10.5152/tjg.2018.18014.

    PMID: 30457558
  15. 15

    Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function.

    Missaglia S, Coleman RA, Mordente A, Tavian D

    Cells 2019; (8(2)) doi:10.3390/cells8020187.

    PMID: 30795549
  16. 16

    Dilated cardiomyopathy caused by mutation of the PNPLA2 gene: a case report and literature review.

    Wang S, Wu S, Peng D

    Frontiers in genetics 2024; (15()):1415156 doi:10.3389/fgene.2024.1415156.

    PMID: 39119584
  17. 17

    Chanarin-Dorfman syndrome: A case report and review of the literature.

    Mogahed EA, El-Hennawy A, El-Sayed R, El-Karaksy H

    Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology 2015; (16(3-4)):142-4.

    PMID: 26520282
  18. 18

    Chanarin-Dorfman syndrome: a novel mutation in a Turkish girl.

    Ünlüsoy-Aksu A, Sarı S, Eğritaş-Gürkan Ö, Dalgıç B

    The Turkish journal of pediatrics 2015; (57(3)):300-3.

    PMID: 26701953
  19. 19

    Jordans' Anomaly as a Red Flag for Neutral Lipid Storage Diseases.

    Safavi M, Vasei M, Motamed F

    Fetal and pediatric pathology 2022; (41(3)):526-528 doi:10.1080/15513815.2020.1831663.

    PMID: 33966594
  20. 20

    Jordans' anomaly in Chanarin-Dorfman syndrome.

    Sánchez-Cortés J, Gabaldó-Barrios X

    Advances in laboratory medicine 2025; (6(1)):118-121 doi:10.1515/almed-2024-0159.

    PMID: 40160390
  21. 21

    [Analysis of genetic variant and phenotype of a child with Chanarin-Dorfman syndrome].

    Zhang M, Zheng K, Shen K, et al.

    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2025; (42(12)):1477-1481 doi:10.3760/cma.j.cn511374-20250731-00470.

    PMID: 41811046
  22. 22

    Two novel heterozygous exonic deletions lead to Chanarin-Dorfman syndrome in a patient with congenital ichthyosis, sensorineural hearing loss, and liver dysfunction.

    Zoullas S, Morel D, Zafeer F, et al.

    American journal of medical genetics. Part A 2024; (194(4)):e63481 doi:10.1002/ajmg.a.63481.

    PMID: 37984424

This page is for informational purposes only and does not constitute medical advice. A dermatologist, geneticist, or other healthcare professional should interpret your ABHD5 results and decide which monitoring is appropriate for you.

Guide contents Neutral lipid storage disease with ichthyosis
Research & Literature
01 Starting Your Journey with Chanarin-Dorfman Syndrome 03 Treatment and Daily Management of Chanarin-Dorfman Syndrome