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HelpTest ID: HSMBS Hepatosplenomegaly Panel, Blood Spot
Ordering Guidance
This test should not be used for monitoring of patients with confirmed diagnoses. If a physician is requesting testing for monitoring purposes, see:
-CTXBS / Cerebrotendinous Xanthomatosis, Blood Spot
-GPSY / Glucopsychosine, Blood Spot
-OXYBS / Oxysterols, Blood Spot
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
Supplies:
-Card-Blood Spot Collection (Filter Paper) (T493)
-Card-Postmortem Screening (Filter Paper) (T525)
Container/Tube:
Preferred: Blood Spot Collection card (Filter Paper)
Acceptable: Whatman Protein Saver 903 filter paper, PerkinElmer 226 filter paper, Munktell filter paper, Postmortem Screening Card, or collected with EDTA, sodium heparin, lithium heparin, or ACD B-containing devices
Specimen Volume: 2 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.
2. Let blood completely dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. At least 1 spot should be complete (ie, unpunched).
4. Do not expose specimen to heat or direct sunlight.
5. Do not stack wet specimens.
6. Keep specimen dry
Additional Information:
1. For collection instructions, see Blood Spot Collection Instructions.
2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777).
3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800).
Forms
1. Biochemical Genetics Patient Information (T602)
2. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Useful For
As a component of the initial evaluation of a patient presenting with hepatosplenomegaly, using dried blood spot specimens
This test is not useful for the identification of carriers.
This test should not be used as a monitoring tool for patients with confirmed diagnoses.
Method Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name
Hepatosplenomegaly Panel, BSSpecimen Type
Whole bloodSpecimen Minimum Volume
1 Blood spot
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole blood | Refrigerated (preferred) | 10 days | FILTER PAPER |
| Frozen | 59 days | FILTER PAPER | |
| Ambient | 10 days | FILTER PAPER |
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
|
Disorder |
Onset |
Analyte detected |
Gene |
Incidence |
|
Cerebrotendinous xanthomatosis (CTX) |
Infancy-adulthood |
7-Alpha-hydroxy-4-cholesten-3-one (7a-C4) 7-Alpha,12-alpha-dihydroxycholest-4-en-3-one (7a12aC4) |
CYP27A1 |
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) |
GBA |
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 A/B (NPA/NPB) |
NPA: neonatal NPB: birth-adulthood |
Lyso-sphingomyelin (LSM) LSM 509 |
SMPD1 |
Combined incidence 1 in 250,000 |
|
Phenotype: 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) |
Variable (perinatal-adulthood) |
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. |
||||
Reference Values
Cholestane-3-beta, 5-alpha, 6-beta-triol
Cutoff: ≤0.800 nmol/mL
Lyso-Sphingomyelin
Cutoff: ≤0.100 nmol/mL
Glucopsychosine
Cutoff: ≤0.040 nmol/mL
7-Alpha-hydroxy-4-cholesten-3-one (7a-C4)
Cutoff: ≤0.750 nmol/mL
7-Alpha,12-alpha-dihydroxycholest-4-en-3-one (7a12aC4)
Cutoff: ≤0.250 nmol/mL
Interpretation
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 particularly of lyso-sphingomyelin (LSM) is highly suggestive of Niemann-Pick type A or B (NPA or NPB) disease.
An elevation of cholestane-3-beta, 5-alpha, 6-beta-triol is highly suggestive of Niemann-Pick disease type C.
An elevation of glucopsychosine is indicative of Gaucher disease.
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(1):146-154
2. Federico A, Dotti MT, Gallus GN. Cerebrotendinous xanthomatosis. In: Adam MP, Feldman J, Mirzaa GM,, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated March 17, 2022. Accessed November 5, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1409/
3. Grabowski GA, Petsko GA, Phil D, 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 November 5, 2024. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225546056&bookid=2709
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, Feldman J, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated April 27, 2023. Accessed November 5, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1370/.
6. Wasserstein M, Dionisi-Vici C, Giugliani R, et al. Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD). Mol Genet Metab. 2019;126(2):98-105
7. Patterson M. Niemann-Pick disease type C. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated December 10, 2020. Accessed November 5, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1296/
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;13(1):50. doi:10.1186/s13023-018-0785-7
Day(s) Performed
Tuesday
Report Available
3 to 9 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
82542
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| HSMBS | Hepatosplenomegaly Panel, BS | 92745-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 601526 | Interpretation (HSMBS) | 59462-2 |
| 601520 | Cholestane-3beta,5alpha,6beta-triol | 92757-4 |
| 601521 | Lyso-sphingomyelin | 92749-1 |
| 601522 | Glucopsychosine | 92752-5 |
| 601523 | 7a-hydroxy-4-cholesten-3-one | 92763-2 |
| 601524 | 7a,12a-dihydroxycholest-4-en-3-one | 92760-8 |
| 601527 | Reviewed By | 18771-6 |
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