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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. Let blood dry completely on filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
2. At least 1 spot should be complete (ie, unpunched).
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. 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. |
||||
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
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
GLOBOTRIAOSYLSPHINGOSINE
Cutoff: ≤0.034 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 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.
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 Jan;55(1):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 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 December 14, 2022 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 Nov;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 www.ncbi.nlm.nih.gov/books/NBK1370/.
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 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 Apr 6;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 |
| 601525 | Globotriaosylsphingosine | 92754-1 |
| 601527 | Reviewed By | 18771-6 |
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