Signs & Symptoms

ASMD symptoms can be multisystemic and life‑threatening1

Suspect ASMD if a patient presents with a combination of these signs and symptoms.1,2

Percentage of patients who experience hallmark signs and symptoms of ASMD*:

>90% of patients with ASMD Type B have splenomegaly
Splenomegaly>90%
>70% of patients with ASMD Type B have hepatomegaly
Hepatomegaly>70%
>80% of patients with ASMD Type B have interstitial lung disease
Interstitial lung disease>80%
>50% of patients with ASMD Type B have thrombocytopenia
Thrombocytopenia>50%
>75% of patients with ASMD have gastrointestinal issues
Gastrointestinal issues>75%

*Symptom prevalence data for splenomegaly, interstitial lung disease, hepatomegaly, and thrombocytopenia are only for patients with ASMD type B. Gastrointestinal issues symptom prevalence is for all ASMD types.1,2

ASMD may be presenting in your practice, know the symptoms

  • Pulmonary symptoms of ASMD include respiratory infections (i.e., pneumonia), interstitial lung disease, chronic fatigue, shortness of breath, and pulmonary hypertension
    • Respiratory infections
      (ie, pneumonia)
    • Interstitial lung disease
    • Shortness of breath
    • Chronic fatigue
    • Pulmonary hypertension
  • Hepatic symptoms of ASMD include hepatomegaly, fibrosis and cirrhosis, elevated transaminases, and dyslipidemia
    • Hepatomegaly
    • Fibrosis and cirrhosis
    • Elevated transaminases
    • Dyslipidemia
  • Splenic symptoms of ASMD include splenomegaly, abdominal pain, pressure, and early satiety due to splenomegaly
    • Splenomegaly
    • Abdominal pain, pressure, and early satiety due to splenomegaly
  • Hematologic symptoms of ASMD include anemia, thrombocytopenia (excessive bleeding and easy bruising)
    • Anemia
    • Thrombocytopenia (excessive bleeding and easy bruising)
  • Gastrointestinal symptoms of ASMD include abdominal pain and diarrhea
    • Abdominal pain
    • Diarrhea
  • Neurological symptoms of ASMD with Types A and A/B include hypotonia, ataxia, developmental delay, and peripheral neuropathy
    • Mainly types A and A/B
    • Hypotonia
    • Ataxia
    • Developmental delay
    • Peripheral neuropathy
  • Ophthalmologic symptoms of ASMD mainly in Types A and A/B include cherry red maculae
    • Mainly types A and A/B
    • Cherry red maculae
  • Cardiac symptoms of ASMD mainly in Types A/B and B include coronary artery disease and EKG abnormalities
    • Mainly types A/B and B
    • Coronary artery disease
    • EKG abnormalities
  • Skeletal symptoms of ASMD include back, limb, and/or joint pain, pathologic fractures, osteopenia/osteoporosis, and growth delay
    • Back, limb, and/or joint pain
    • Pathologic fractures
    • Osteopenia/Osteoporosis
    • Growth delay

ASMD signs and symptoms commonly mimic other conditions3

Symptoms of ASMD often overlap those of other lysosomal storage disorders, hematologic malignancies, and diseases of the heart and lungs. As a result, misdiagnosis and diagnostic delays are common.3

Conditions that share the hallmark signs and symptoms of ASMD include Gaucher disease type 1, acute lymphoblastic leukemia, non-Hodgkin lymphoma, chronic hepatitis B, cystic fibrosis, and congestive heart failure.3

Gaucher disease – another rare lysosomal storage disorder – shares significant phenotypic overlap with ASMD. Similar to ASMD, Gaucher disease is characterized by multisystemic and progressive symptoms that vary in onset and clinical presentation.3,7

ASMD and Gaucher disease often present with symptoms similar to more commonly seen conditions1,3,7-20

 ASMD  Gaucher
disease
Acute
lymphoblastic
leukemia
Non-
Hodgkin
lymphoma
Chronic
hepatitis B
Congestive
heart failure
Cystic
fybrosis
Hepatomegaly/
Splenomegaly
· · · · · · ·
Anemia · · · · ·
Thrombocytopenia · · · · · ·
Fatigue · · · · · · ·
Bone pain · · · ·
Abdominal pain · · · · · · ·
Growth delay · ·
Liver fibrosis* · · ·
Interstitial lung disease* ·
Dyslipidemia* ·
Elevated transaminases · · ·

The dots in the table above represent the most commonly presenting symptoms in each of the respective diseases.

*This symptom is not seen as commonly in Gaucher disease type 1.

Include ASMD and Gaucher disease in your differential diagnosis, along with other, more commonly seen and considered conditions. Your differential diagnosis can help patients find the answer to their progressive symptoms.
Prevent diagnosis delays
Prevent Diagnosis Delays
Understand the disease burden on patients
Understand the Disease Burden on Patients
References:
  1. McGovern MM, Avetisyan R, Sanson BJ, Lidove O. Orphanet J Rare Dis. 2017;12(1):41.
  2. Cox GF, Clarke LA, Giugliani R. JIMD Rep. 2018;41:119-129.
  3. McGovern MM, Dionisi-Vici C, Giugliani R, et al. Genet Med. 2017;19(9):967-974.
  4. McGovern MM, Aron A, Brodie SE, Desnick RJ, Wasserstein MP. Neurology. 2006;66(2):228-232.
  5. McGovern MM, Wasserstein MP, Giugliani R, et al. Pediatrics. 2008;122(2):e341-e349.
  6. Cassiman D, Packman S, Bembi B, et al. Mol Genet Metab. 2016;118(3):200-213.
  7. Kaplan P, Baris H, de Meirleir L, et al. Eur J Pediatr. 2013;172:447-458.
  8. Mistry PK, Capellini MD, Lukina E, et al. Am J Hematol. 2011;86(1):110-115.
  9. Grabowski GA, Petsko GA, Kolodny EH. http://ommbid.mhmedical.com/content.aspx?bookid=474§ionid=45374148. Accessed April 8, 2020.
  10. Stirnemann J, Belmatoug N, Camou F, et al. Int J Mol Sci. 2017;18(2):441.
  11. De Fost M, Langeveld M, Franssen R, et al. Atherosclerosis. 2009;204(1):267-272.
  12. Leukemia & Lymphoma Society. https://www.lls.org/leukemia/acute-lymphoblastic-leukemia/signs-and-symptoms. Accessed April 8, 2020.
  13. Larson RA, Anastasi J. Hematologic Malignancies: Acute Leukemias. 2008.
  14. Leukemia & Lymphoma Society. https://www.lls.org/lymphoma/non-hodgkin-lymphoma/signs-and-symptoms. Accessed April 8, 2020.
  15. American Cancer Society. https://www.cancer.org/cancer/non-hodgkin-lymphoma/treating/palliative-care.html. Accessed April 8, 2020.
  16. Shankland KR, Armitage JO, Hancock BW. Lancet. 2012;380(9844):848-857.
  17. National Cancer Institute, National Institutes of Health. https://www.cancer.gov/types/lymphoma/patient/adultnhl-treatment-pdq. Accessed April 8, 2020.
  18. Liang TJ. Hepatology. 2009;49(5 suppl):S13-S21.
  19. Watson RDS, Gibbs CR, Lip GYH. BMJ. 2000;320(7229):236-239.
  20. Kobelska-Dubiel N, Klincewicz B, Cichy W. Prz Gastroenterol. 2014;9(3):136-141.