Test Id : HSMBS
Hepatosplenomegaly Panel, Blood Spot
Useful For
Suggests clinical disorders or settings where the test may be helpful
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.
Highlights
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.
Method Name
A short description of the method used to perform the test
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
ASM Deficiency
Niemann-Pick type A
Niemann-Pick type B
Niemann-Pick type C
Cerebral cholesterinosis
Cerebrotendinous cholesterosis
Van Bogaert-Scherer-Epstein syndrome
Sterol 27-hydrolase deficiency
Ketosterols
Beta glucosidase deficiency
ASMD
Acid Sphingomyelinase Deficiency
Specimen Type
Describes the specimen type validated for testing
Whole blood
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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
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).
Special Instructions
Library of PDFs including pertinent information and forms related to the test
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.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
1 Blood spot
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Shows serum rings Insufficient specimen Layering Multiple applications | Reject |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole blood | Refrigerated (preferred) | 10 days | FILTER PAPER |
| Ambient | 10 days | FILTER PAPER | |
| Frozen | 59 days | FILTER PAPER |
Useful For
Suggests clinical disorders or settings where the test may be helpful
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.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Cholestane-3-beta, 5-alpha, 6-beta-triol
Cutoff: < or =0.800 nmol/mL
Lyso-Sphingomyelin
Cutoff: < or =0.100 nmol/mL
Glucopsychosine
Cutoff: < or =0.040 nmol/mL
7-Alpha-hydroxy-4-cholesten-3-one (7a-C4)
Cutoff: < or =0.750 nmol/mL
7-Alpha,12-alpha-dihydroxycholest-4-en-3-one (7a12aC4)
Cutoff: < or =0.250 nmol/mL
Interpretation
Provides information to assist in interpretation of the test results
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.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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
Recommendations for in-depth reading of a clinical nature
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
Method Description
Describes how the test is performed and provides a method-specific reference
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)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Tuesday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
82542
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| HSMBS | Hepatosplenomegaly Panel, BS | 92745-9 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 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 |