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PubMed This is a summary of 13 peer-reviewed journal articles Updated
Medical Genetics

Understanding the Two Forms of LAL-D

At a Glance

Lysosomal Acid Lipase Deficiency (LAL-D) is a progressive disease that occurs on a spectrum. The severe infantile-onset form (formerly Wolman disease) appears rapidly in babies, while the later-onset form (formerly CESD) can present at any age with progressive liver damage and high cholesterol.

Lysosomal Acid Lipase Deficiency (LAL-D) is a single disease that exists on a continuous spectrum of severity [1][2]. While doctors previously used two separate names (Wolman disease and CESD), modern medicine now views these as the same condition, categorized by when symptoms first appear: Infantile-onset LAL-D and Later-onset LAL-D [3][4].

The severity of the disease is generally tied to how much residual enzyme activity a person has—essentially, how much “working” enzyme the body is still producing [1].

Infantile-Onset LAL-D (Wolman Disease)

This is the most severe form of the disease, typically occurring in infants with less than 1% of normal enzyme activity [1]. Symptoms appear rapidly within the first weeks or months of life [3].

  • Failure to Thrive: This is often the first sign, where an infant cannot gain weight or grow as expected [3][5].
  • Severe Malabsorption: Because fats cannot be processed, they build up in the intestines, causing chronic diarrhea and oily stools [3].
  • Organ Enlargement: The liver and spleen often become significantly enlarged (hepatosplenomegaly), leading to a swollen or distended abdomen [6][5].
  • Adrenal Calcification: A unique hallmark of this form is bilateral adrenal calcification [6]. In the vast majority (often over 80%) of these infants, calcium deposits form in the adrenal glands, which can be seen on an X-ray or CT scan [6]. This can lead to adrenal insufficiency, where the body cannot produce enough vital hormones [6].

Later-Onset LAL-D (CESD)

Later-onset LAL-D (Cholesteryl Ester Storage Disease) can be diagnosed at any age—from early childhood through adulthood [3]. These individuals usually have a small amount of working enzyme, which slows the progression of the disease [1].

Because the symptoms are often “silent” or mimic more common conditions, many people are misdiagnosed with NAFLD (non-alcoholic fatty liver disease) or general high cholesterol [3][7].

  • Liver Progression: If untreated, the liver continuously stores fat, leading to inflammation and fibrosis (scarring) [1][8]. Over time, this can progress to cirrhosis (advanced scarring) or liver failure [9][10].
  • Abnormal Lipid Profile: Patients typically show a characteristic pattern: very high LDL (“bad” cholesterol) and triglycerides, combined with very low HDL (“good” cholesterol) [3][11].
  • Cardiovascular Risk: Because these abnormal fat levels begin at such a young age, patients are at a high risk for premature atherosclerosis (hardening of the arteries), which can lead to early heart attacks or strokes [11][12].

A Progressive Spectrum

Regardless of the age of onset, LAL-D is a progressive condition. This means that without targeted treatment, the buildup of fats continues to damage organs over time [1][13]. The shift in nomenclature to “Infantile” and “Later-onset” emphasizes that while the timing may differ, the underlying cause—and the need for specialized care—remains the same [2][4].

Common questions in this guide

What is the difference between Wolman disease and CESD?
Wolman disease and CESD are now recognized as two forms of the exact same underlying condition, known as LAL-D. Wolman disease refers to the severe infantile-onset form, while CESD refers to the later-onset form that can appear in childhood or adulthood.
What are the early signs of infantile-onset LAL-D?
Early signs usually appear within the first weeks or months of life. They include an inability to gain weight (failure to thrive), severe chronic diarrhea with oily stools, and significant enlargement of the liver and spleen.
Why is later-onset LAL-D often misdiagnosed?
The symptoms of later-onset LAL-D are often silent or mimic more common health issues. Because of this, many patients are incorrectly diagnosed with non-alcoholic fatty liver disease (NAFLD) or general high cholesterol before receiving an accurate LAL-D diagnosis.
How does LAL-D affect the liver over time?
Because the body cannot process fats properly, fat continuously builds up in the liver. Without treatment, this leads to ongoing inflammation, scarring (fibrosis), and can eventually progress to advanced cirrhosis or liver failure.
What happens to cholesterol levels in later-onset LAL-D?
Patients typically develop a very specific abnormal lipid profile from a young age. This includes very high levels of LDL (bad cholesterol) and triglycerides, combined with very low levels of HDL (good cholesterol), which increases the risk of premature heart disease.
What does adrenal calcification mean for infants with LAL-D?
A unique hallmark of infantile-onset LAL-D is bilateral adrenal calcification. Calcium deposits form in the adrenal glands, which can lead to adrenal insufficiency where the body cannot produce enough vital hormones.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on the genetic results, where on the LAL-D spectrum does my diagnosis (or my child's) fall?
  2. 2.If I have the infantile form, have my child's adrenal glands been checked for calcification or insufficiency?
  3. 3.For later-onset LAL-D, what is the current stage of my liver health (fibrosis or scarring)?
  4. 4.What is my current risk for early cardiovascular disease based on my lipid levels?
  5. 5.Should we be monitoring for malabsorption or nutritional deficiencies?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (13)
  1. 1

    A rare cause of hepatomegaly in the childhood: Lysosomal acid lipase deficiency.

    Haznedar P, Kuloğlu Z, Kansu A, Eminoğlu FT

    The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 2018; (29(4)):518-519 doi:10.5152/tjg.2018.17492.

    PMID: 30249571
  2. 2

    Lysosomal acid lipase deficiency in Brazilian children: a case series.

    Benevides GN, Miura IK, Person NC, et al.

    Jornal de pediatria 2019; (95(5)):552-558 doi:10.1016/j.jped.2018.05.016.

    PMID: 31340901
  3. 3

    The Emerging Battle: Lysosomal Acid Lipase Deficiency vs Familial Hypercholesterolemia in Children.

    Saad M, Syed S

    ACG case reports journal 2021; (8(1)):e00516 doi:10.14309/crj.0000000000000516.

    PMID: 33457437
  4. 4

    Diagnostic and therapeutic management of children with lysosomal acid lipase deficiency (LAL-D). Review of the literature and own experience.

    Wierzbicka-Rucińska A, Jańczyk W, Ługowska A, et al.

    Developmental period medicine 2016; (20(3)):212-215.

    PMID: 27941191
  5. 5

    Wolman Disease: A Mimic of Infant Leukemia.

    Gopakumar KG, Thankamony P, Nampoothiri S, et al.

    Journal of pediatric hematology/oncology 2017; (39(8)):e489-e492 doi:10.1097/MPH.0000000000000861.

    PMID: 28538091
  6. 6

    CT features of Wolman disease (lysosomal acid lipase enzyme deficiency) - A case report.

    Foladi N, Aien MT

    Radiology case reports 2021; (16(10)):2857-2861 doi:10.1016/j.radcr.2021.06.084.

    PMID: 34401013
  7. 7

    Managing Cardiovascular Risk in Lysosomal Acid Lipase Deficiency.

    Maciejko JJ

    American journal of cardiovascular drugs : drugs, devices, and other interventions 2017; (17(3)):217-231 doi:10.1007/s40256-017-0216-5.

    PMID: 28197978
  8. 8

    Progression of liver disease in children and adults with lysosomal acid lipase deficiency.

    Burton BK, Silliman N, Marulkar S

    Current medical research and opinion 2017; (33(7)):1211-1214 doi:10.1080/03007995.2017.1309371.

    PMID: 28320214
  9. 9

    Lysosomal acid lipase deficiency: a form of non-obese fatty liver disease (NOFLD).

    A-Kader HH

    Expert review of gastroenterology & hepatology 2017; (11(10)):911-924 doi:10.1080/17474124.2017.1343144.

    PMID: 28612634
  10. 10

    A Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant.

    Anushiravani A, Jafari Khamirani H, Mohamadkhani A, et al.

    Archives of Iranian medicine 2023; (26(2)):86-91 doi:10.34172/aim.2023.14.

    PMID: 37543928
  11. 11

    Cholesterol trafficking-related serum lipoprotein functions in children with cholesteryl ester storage disease.

    Zimetti F, Favari E, Cagliero P, et al.

    Atherosclerosis 2015; (242(2)):443-9.

    PMID: 26291497
  12. 12

    Benefit of Treatment With Sebelipase-Alfa in a 63-Year-Old Patient With Advanced Liver and Atherosclerotic Disease Due to Lysosomal Acid Lipase Deficiency (LAL-D).

    Aigner E, Feldman A, Neureiter D, et al.

    The American journal of gastroenterology 2018; (113(3)):443-445 doi:10.1038/ajg.2017.486.

    PMID: 29535442
  13. 13

    Survival, growth, and safety findings in patients with rapidly progressive, infantile-onset LAL-D: Results from the international LAL-D registry.

    Vijay S, Evans J, Lacaille F, et al.

    Molecular genetics and metabolism 2025; (146(4)):109290 doi:10.1016/j.ymgme.2025.109290.

    PMID: 41270440

This page is for informational purposes only and does not replace professional medical advice. Always consult your hepatologist, pediatrician, or medical geneticist about your specific LAL-D diagnosis and monitoring needs.

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