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Test Code 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

Disorder

Onset

Analyte detected

Gene

Incidence

Cerebrotendinous xanthomatosis (CTX) 

Infancy - adulthood

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

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

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 (7aC4)

Cutoff: ≤0.750 nmol/mL

 

7-ALPHA,12-ALPAH-DIHYDROXYCHOLEST-4-en-3-ONE (12aC4)

Cutoff: ≤0.250 nmol/mL

 

GLOBOTRIAOSYLSPHINGOSINE

Cutoff: ≤0.034 nmol/mL

Day(s) Performed

Tuesday

Report Available

3 to 9 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test 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