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Test ID HSMWB Hepatosplenomegaly Panel, Blood

Ordering Guidance

This test should not be used for monitoring patients with confirmed diagnoses. If the testing requested is for monitoring purposes, see:

-CTXWB / Cerebrotendinous Xanthomatosis, Blood

-GPSYW / Glucopsychosine, Blood

-OXYWB / Oxysterols, Blood


This test's clinical sensitivity and specificity for the identification of Niemann-Pick type C (NPC) is 75% and 89%, respectively. If NPC is strongly suspected, the recommended test is HSMP / Hepatosplenomegaly Panel, Plasma.

Specimen Required

Collection Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Green top (sodium heparin, lithium heparin), yellow top (ACD B)

Specimen Volume: 1 mL

Collection Instructions: Send whole blood specimen in original vial. Do not aliquot.

Useful For

As a component of the initial evaluation of a patient presenting with hepatosplenomegaly


This test is not useful for the identification of carriers.


This test should not be used as a monitoring for patients with confirmed diagnoses.

Method Name

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Reporting Name

Hepatosplenomegaly Panel, B

Specimen Type

Whole blood

Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole blood Refrigerated (preferred) 72 hours
  Ambient  48 hours

Reject Due To

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Clinical Information

Hepatosplenomegaly is a presenting or accompanying feature for many different inborn errors of metabolism. It typically is a consequence of chronic hepatic dysfunction or abnormal storage of lipids, sugars, or other improperly metabolized analytes due to a particular enzymatic deficiency. The diagnosis can occasionally be narrowed down by consideration of clinical symptoms; however, clinical diagnosis can be difficult due to similarity of clinical features across disorders as well as phenotypic variability. Therefore, screening tests can play an important role in the workup of a patient presenting with hepatosplenomegaly who may have a lysosomal or lipid storage disorder.


The conditions detected in this assay are cerebrotendinous xanthomatosis, Gaucher disease, and Niemann-Pick (NP) disease types A, B (also known as acid sphingomyelinase deficiency), and, with a lower sensitivity and specificity, NPC.


Patients with abnormal results should have follow-up enzymatic or molecular testing for confirmation of diagnosis.


Table. Conditions Identifiable by Method



Analyte detected



Cerebrotendinous xanthomatosis (CTX) 

Infancy - adulthood

7-Alpha-hydroxy-4-cholesten-3-one (7aC4)

7-Alpha,12-aplha-dihydroxycholest-4-en-3-one (12aC4)


1 in 50,000

As high as 1 in 400 in Druze population.

Phenotype: Early onset diarrhea, cataracts, tendon/cerebral xanthomas, osteoporosis, neuropsychological manifestations, liver disease/hepatosplenomegaly.

Gaucher disease

Type I: childhood/adult

Types II/III: neonatal-early childhood

Glucopsychosine (GPSY)


Type I:

1 in 30,000 to 1 in 100,000

Types II/III:

1 in 100,000

Phenotype: All types exhibit hepatosplenomegaly and hematological abnormalities.

Type I: Organomegaly, thrombocytopenia, and bone pain. Absence of neurologic symptoms.

Types II/III: Primary neurologic disease, developmental delay/regression, hepatosplenomegaly, lung disease. Patients with type II typically die by 2 to 4 years of age. Patients with type III may have a less progressive phenotype and may survive into adulthood.

Niemann-Pick type


NPA: neonatal

NPB: birth-adulthood

Lyso-sphingomyelin (LSM)

LSM 509


Combined incidence

1 in 250,000


NPA: Feeding difficulties, jaundice, hepatosplenomegaly, neurologic deterioration, lung disease, hearing and vision impairment, cherry red macula, death usually by 3 years of age.

NPB: Mainly limited to visceral symptoms; hepatosplenomegaly, stable liver dysfunction, pulmonary compromise, osteopenia.

Niemann-Pick type C (NPC)



Cholestane-3 beta, 5 alpha, 6 beta-triol (COT)

LSM 509

NPC1 or NPC2

1 in 120,000 to 1 in 150,000

Phenotype: Variable clinical presentation; ataxia, vertical supranuclear gaze palsy, dystonia, progressive speech deterioration, seizures, ± hepatosplenomegaly.


Patients with Fabry disease may also be identified by this assay. The glycosphingolipid, globotriaosylsphingosine (LGb3), may be elevated in symptomatic patients and supports a diagnosis of Fabry disease. Normal values of LGb3 do not rule out Fabry disease. Patients with Fabry disease do not have hepatosplenomegaly as an accompanying feature.

Reference Values


Cutoff: ≤0.800 nmol/mL



Cutoff: ≤0.100 nmol/mL



Cutoff: ≤0.040 nmol/mL



Cutoff: ≤0.750 nmol/mL



Cutoff: ≤0.250 nmol/mL



Cutoff: ≤0.034 nmol/mL


An elevation of 7-alpha-hydroxy-4-cholesten-3-one (7aC4) and 7-alpha,12-alpha-dihydroxycholest-4-en-3-one (12aC4) is strongly suggestive of cerebrotendinous xanthomatosis.


An elevation of lyso-sphingomyelin (LSM) and LSM 509 is highly suggestive of Niemann-Pick type A or B disease.


An elevation of cholestane-3 beta, 5 alpha, 6 beta-triol and LSM 509 is highly suggestive of Niemann-Pick disease type C.


An elevation of glucopsychosine is indicative of Gaucher disease.


Patients with Wolman disease or cholestatic biliary atresia may have a profile similar to Niemann-Pick disease type C.


Patients with bile acid malabsorption or ileal resection may have elevations of 7-alpha-hydroxy-4-cholesten-3-one (7aC4).


This test does not identify all causes of hepatosplenomegaly.


A positive test result is strongly suggestive of a diagnosis but needs follow-up by stand-alone biochemical or molecular assay.

Clinical Reference

1. DeBarber AE, Luo J, Star-Weinstock M, et al: A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns. J Lipid Res. 2014;55:146-154

2. Federico A, Dotti MT, Gallus GN: Cerebrotendinous xanthomatosis. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated April 14, 2016. Accessed December 14, 2022. Available at

3. Grabowski GA, Petsko GA, Kolodny EH: Gaucher disease. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed December 14, 2022. Available at

4. Murugeasan V, Chuan WL, Liu J, et al: Glucosylsphingosine is a key biomarker of Gaucher disease. Am J Hematol. 2016;91(11):1082-1089

5. Wasserstein MP, Schuchman EH. Acid sphingomyelinase deficiency. In: Adam MP, Everman DB, Mirzaa GM, et al., eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated February 25, 2021. Accessed December 14, 2022. Available at

6. Wasserstein M, Dionisi-Vici C, Giugliani R, Hwu WL, Lidove O, Lukacs Z, Mengel E, Mistry PK, Schuchman EH, McGovern M. Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD). Mol Genet Metab. 2019 Feb;126(2):98-105

7. Patterson M: Niemann-Pick disease type C. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated December 10, 2020. Accessed December 14, 2022. Available at

8. Geberhiwot T, Moro A, Dardis A, et al; International Niemann-Pick Disease Registry (INPDR): Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis. 2018 Apr 6;13(1):50. doi: 10.1186/s13023-018-0785-7

Method Description

Whole blood is spotted on filter paper and dried overnight. A 3-mm dried blood spot is extracted with internal standard. The extract is subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The MS/MS is operated in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for each analyte and internal standard. The ratio of the extracted peak areas to internal standard determined by the LC-MS/MS is used to calculate the concentration of in the sample.(Unpublished Mayo method)

Day(s) Performed


Report Available

3 to 9 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
HSMWB Hepatosplenomegaly Panel, B 92744-2


Result ID Test Result Name Result LOINC Value
601534 Interpretation (HSMWB) 59462-2
601528 Cholestane-3beta,5alpha,6beta-triol 92756-6
601529 Lyso-sphingomyelin 92748-3
601530 Glucopsychosine 92751-7
601531 7a-hydroxy-4-cholesten-3-one 92762-4
601532 7a,12a-dihydroxycholest-4-en-3-one 92759-0
601533 Globotriaosylsphingosine 92753-3
601535 Reviewed By 18771-6


This is a screening test for a select number of lysosomal and lipid storage disorders, including cerebrotendinous xanthomatosis, Gaucher disease, and Niemann-Pick disease types A, B (also known as acid sphingomyelinase deficiency), and C.


The above conditions may all have hepatosplenomegaly as a presenting sign, making this test a helpful component of a patient's initial evaluation.


Although Fabry disease does not have hepatosplenomegaly as a clinical symptom, it can be identified by this assay as the compound, globotriaosylsphingosine, is detected.