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Test 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, HSMP / Hepatosplenomegaly Panel, Plasma is recommended.



Specimen Required


Supplies:

-Card-Blood Spot Collection (Filter Paper) (T493)

-Card-Postmortem Screening (Filter Paper) (T525)

Container/Tube:

Preferred: Blood Spot Collection card

Acceptable: Ahlstrom 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 in Special Instructions.

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.


Forms

1. Biochemical Genetics Patient Information (T602) in Special Instructions.

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 suitable 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, BS

Specimen Type

Whole blood

Specimen 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 disease types A, B, and with a lower sensitivity and specificity C.

 

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

 

Conditions Identifiable By Method

Disorder

Onset

Analyte detected

Gene

Incidence

Cerebrotendinous xanthomatosis (CTX)

 

 

 

Infancy-adulthood

7-aApha-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 age 2 to 4. Patients with Type 3 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)

lyso-sphingomyelin 509 (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 age 3.

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)

lyso-sphingomyelin 509 (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 (7a-C4) and 7-alpha,12-alpha-dihydroxycholest-4-en-3-one (7a12aC4) is strongly suggestive of cerebrotendinous xanthomatosis (CTX).

 

An elevation of lyso-sphingomyelin (LSM) and lyso-sphingomyelin 509 (LSM 509) 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 (COT) lyso-sphingomyelin 509 (LSM 509) is highly suggestive of Niemann-Pick disease type C (NPC).

 

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, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated April 14, 2016. Accessed November 20, 2020. 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 February 4, 2021. 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. Patterson M: Niemann-Pick disease type C. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated August 29, 2019. Accessed February 4, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1296/

Day(s) Performed

Tuesday

Report Available

2 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

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
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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