What Are the Signs and Symptoms of ASMD?

ASMD types A/B and B: Manifestations progress less rapidly than in type A and may include any combination of the following¹

Hepatomegaly is seen in>70% of patients^1,2*
Symptoms of hepatomegaly include enlarged abdomen and abdominal pain^1,3

	LIVER Hepatomegaly Fibrosis and cirrhosis Dyslipidemia
	SPLEEN Splenomegaly (can be up to 30 times normal size) Pain, pressure, and early satiety due to enlarged spleen
	LUNGS Interstitial lung disease (ILD) Respiratory infections, including pneumonia Shortness of breath and chronic fatigue
	HEMATOLOGIC Thrombocytopenia Excessive bleeding and easy bruising Anemia Leukopenia

	NEUROLOGIC Severe abnormalities (cognitive impairment, loss of motor function, etc) Hypotonia/hyporeflexia
	CARDIAC Coronary artery or heart valve disease
	SKELETAL Back, limb, and/or joint pain Pathologic fractures Osteopenia Osteoporosis in adults
	GROWTH AND DEVELOPMENT Growth delay and puberty delay in adolescents, withadult heights in the low-normal range Excessive bleeding and easy bruising Delays in reaching developmental milestones in children Learning disabilities, changes in behavior,and/or loss of mobility and coordination

^*Symptom prevalence data for hepatomegaly is only for patients with ASMD type B.

References

McGovern MM, et al. Orphanet J Rare Dis. 2017;12(1):41. doi:10.1186/s13023-017-0572-x
Cox GF, et al. JIMD Rep. 2018;41:119-129.
National Organization for Rare Disorders. Acid sphingomyelinase deficiency. Accessed February 3, 2023. https://rarediseases.org/rare-diseases/acid-sphingomyelinase-deficiency/?filter=Signs%2B%26%2BSymptomsa.

Potential Hepatic Manifestations of ASMD Often Overlap With Hepatic Disorders and Other Lysosomal Storage Diseases¹

Potential hepatic symptoms of ASMD	ASMD¹	Chronic hepatitis B^1-3	Nonalcoholic fatty liver disease^4,5	Cryptogenic cirrhosis^1,6,7	Niemann-Pick disease type C^1,8,9	Lysosomal acid lipase deficiency^1,10,11	Gaucher disease^1,12,13
Hepatomegaly
Elevated hepatic enzymes
Fibrosis/cirrhosis
Hepatic failure
Portal hypertension

^*Aminotransferase levels, such as AST and ALT, are typically only mildly elevated or normal in those with cryptogenic cirrhosis.⁶
^†Development of end-stage liver disease is rare with Gaucher disease and tends to include the associated complications of hepatic decompensation.¹²
ALT=alanine aminotransferase; ASMD=acid sphingomyelinase deficiency; AST=aspartate aminotransferase.

References

McGovern MM, et al. Genet Med. 2017;19(9):967-974.
Hepatitis B Foundation. Other Tests. Accessed February 3, 2023. https://www.hepb.org/prevention-and-diagnosis/diagnosis/other-tests/#:~:text=If%20a%20person%20is%20infected,risk%20of%20potential% 20liver%20damage
Terrault NA, et al. Hepatology. 2018;67(4):1560-1599.
Chalasani N, et al. Hepatology. 2018;67(1):328-357.
Miao L, et al. Port Hypertens Cirrhos. 2022;1:57-65.
Patel N, et al. Cryptogenic cirrhosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 12, 2022.
Mercado-Irizarry A, et al. Clin Liver Dis (Hoboken). 2016;7(4):69-72.
Rodriguez-Gil JL, et al. Am J Med Genet A. 2021;185(10):3111-3117.
Twarling A, et al. J Diagn Med Sonogr. 2004;20(4):198-201.
Hoffman EP, et al. Lysosomal Acid Lipase Deficiency. In: Adam MP, et al, eds. GeneReviews^®. University of Washington, Seattle; 2015. Initial posting July 30, 2015; last update September 1, 2016. Accessed January 30, 2023. https://www.ncbi.nlm.nih.gov/books/NBK305870/.
Strebinger G, et al. Hepat Med. 2019;11:79-88.
Adar T, et al. Blood Cells Mol Dis. 2018;68:66-73.
Starosta RT, et al. Mol Genet Metab Rep. 2020;22:100564. doi:10.1016/j.ymgmr.2019.100564.