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Test ID: HSAN1 Hereditary Sensory and Autonomic Neuropathy, Type I, Serum


Necessary Information


The following information is required for interpretation of results:

1. Patient's age

2. Reason for testing

3. Diabetic diagnosis



Specimen Required


Patient Preparation: Fasting 8 hours

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL


Useful For

Diagnosis of patients with clinical features suggestive of hereditary sensory and autonomic neuropathy, type I caused by variants in SPTLC1 and SPTLC2

 

Monitoring of patients with hereditary sensory and autonomic neuropathy, type I caused by variants in SPTLC1 and SPTLC2

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Reporting Name

Hereditary Sensory Neuropathy I, S

Specimen Type

Serum

Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 90 days
  Refrigerated  24 hours

Clinical Information

Sphingolipids, a class of lipids derived from sphingosine, are essential components of plasma membranes and lipoproteins. They are synthesized from L-serine and palmitoyl-CoA by the enzyme serine palmitoyltransferase. Deoxysphingolipids (dSL) are atypical sphingolipids derived from the amino acids alanine or glycine instead of L-serine and cannot be degraded by normal catabolic pathways. Pathologically elevated dSL have been identified as potential biomarkers in a variety of conditions such as hereditary sensory and autonomic neuropathy type 1 (HSAN1), type 2 diabetes mellitus, metabolic syndrome, mitochondrial disease, glycogen storage disease type 1, and possibly disorders of serine biosynthesis.

 

Hereditary sensory and autonomic neuropathies are a group of clinically and genetically heterogeneous peripheral neuropathies. HSAN1 is inherited in an autosomal dominant fashion and is typically characterized by a later onset loss of pain and temperature sensation in the hands and feet, which can be accompanied by shooting pain attacks, lancinating pain, and skin ulcers predominantly affecting the lower limbs.

 

While variants in 5 different genes (SPTLC1, SPTLC2, ATL1, RAB7A and DNMT1) have been linked to HSAN1, the majority of variants are in SPTLC1 and SPTLC2, which encode 2 of 3 subunits of the serine palmitoyltransferase (SPT) enzyme. Variants in these 2 genes lead to a shift in SPT substrate specificity from L-serine to L-alanine, which ultimately produces 2 neurotoxic deoxysphingolipids, 1-deoxymethylsphinganine and 1-deoxysphinganine. The accumulation of these metabolites in the cells and serum of affected patients is thought to cause the clinical features associated with HSAN1. A recent clinical trial found that L-serine supplementation safely reduced levels of 1-deoxysphingolipids in humans and suggested that supplementation may offer a clinical benefit.(1)

Reference Values

Sphinganine: ≤18.0 ng/mL

1-deoxysphinganine: ≤0.25 ng/mL

1-deoxymethylsphinganine: ≤0.04 ng/mL

Sphingosine: ≤80.0 ng/mL

1-deoxysphingosine: ≤0.05 ng/mL

1-deoxymethylsphingosine: ≤0.09 ng/mL

Interpretation

Elevation of deoxysphingolipids may indicate hereditary sensory and autonomic neuropathy, type I caused by variants in SPTLC1 and SPTLC2.

 

Deoxysphingolipids may also be elevated in patients with other conditions such as type 2 diabetes mellitus, metabolic syndrome, mitochondrial disorders, glycogen storage disease type 1, and possibly disorders of serine biosynthesis.

Clinical Reference

1. Fridman V, Suriyanarayanan S, Novak P, et al: Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. Neurology. 2019 Jan 22;92(4):e359-e370. doi: 10.1212/WNL.0000000000006811

2. Astudillo L, Sabourdy F, Therville N, et al: Human genetic disorders of sphingolipid biosynthesis. J Inherit Metab Dis. 2015 Jan;38(1):65-76

3. Gable K, Gupta SD, Han G, Niranjanakumari S, Harmon JM, Dunn TM: A disease-causing mutation in the active site of serine palmitoyltransferase causes catalytic promiscuity. J Biol Chem. 2010 Jul 23;285(30):22846-22852

4. Penno AK, Reilly MM, Houlden H, et al: Hereditary sensory neuropathy type I is caused by the accumulation of two neurotoxic sphingolipids. J Biol Chem. 2010 Apr 9;285(15):11178-11187

5. Lone MA, Santos T, Alecu I, Silva LC, Hornemann T: 1-Deoxysphingolipids. 2019 Apr;1864(4):512-521. doi: 10.1016/j.bbalip.2018.12.013

6. Ferreira CR, Goorden SMI, Soldatos A, et al: Deoxysphingolipid precursors indicate abnormal sphingolipid metabolism in individuals with primary and secondary disturbances of serine availability. Mol Genet Metab. 2018 Jul;124(3):204-209. doi: 10.1016/j.ymgme.2018.05.001

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
HSAN1 Hereditary Sensory Neuropathy I, S In Process

 

Result ID Test Result Name Result LOINC Value
BG718 Reason for Referral 42349-1
BG719 Diabetic diagnosis In Process
605993 1-deoxysphinganine In Process
605996 1-deoxysphingosine In Process
605994 1-deoxymethylsphinganine In Process
605997 1-deoxymethylsphingosine In Process
605992 Sphinganine In Process
605995 Sphingosine In Process
605998 Interpretation (HSAN1) 59462-2
605991 Reviewed By 18771-6

Report Available

8 to 15 days

Day(s) Performed

Thursday

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical