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Metachromatic Leukodystrophy via the PSAP Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
PSAP 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7169PSAP81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

Metachromatic leukodystrophy (MLD, OMIM 250100) is a lysosomal storage disorder due to the abnormal degradation of sulfatide and its subsequent accumulation, mainly in the nervous system. The lysosomal degradation of sulfatide requires both the enzyme arylsulfatase A (ARSA) and the sphingolipid-activator protein 1 (SAP-1). While most patients with MLD have deficiency in the ARSA enzyme, some patients have deficiency in SAP-1. MLD is a progressive neurodegenerative disease. Three clinical subtypes are distinguished on the basis of the age of onset:

1) Late infantile MLD is characterized by onset before the age of two years and death by the age of five. Symptoms begin with a decline of physical and mental abilities after a few months of normal development and progress to blindness, deafness, paralysis, and difficulty in swallowing (Masters et al. Arch Dis Child 39:345-355, 1964).

2) Juvenile MLD is characterized by onset between five and ten years of age and death by the age of twenty. Symptoms include slow deterioration of speech, gait and posture, spasticity, and dystonia (Schutta et al. J Med Genet 3:86-91, 1966).

3) Adult MLD is characterized by onset after the age of sixteen, unsteady gait, and slow neurological progression with cognitive loss (Müller et al. J Neurol Sci 9:567-584, 1969).


All forms of MLD are inherited with an autosomal recessive manner; they are caused by variants in the ARSA gene (Gieselmann et al. Proc Natl Acad Sci USA 86:9436-9440, 1989) or the PSAP gene (Kretz et al. Proc Natl Acad Sci USA 87:2541-2544, 1990). To date, 17 PSAP variants have been reported. They are distributed along the entire coding region of the gene and occurred in patients from various ethnic groups. Variants include missense, nonsense, splicing, and small insertions. In addition to MLD, variants in the PSAP gene were reported in patients with Gaucher disease (Schnabel et al. FEBS Lett 284:57-59, 1991; Diaz-Font et al. Hum Genet 117:275-277, 2005), patients with Krabbe disease (Spiegel et al. Mol Genet Metab 84:160-166, 2005) and patients with combined saposin deficiency (Schnabel et al. J Biol Chem 267:3312-3315, 1992). The PSAP gene encodes the sphingolipid activator protein 1 (SAP-1).

Clinical Sensitivity - Sequencing with CNV PG-Select

Currently not known.

Testing Strategy

This test provides full coverage of all coding exons of the PSAP gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with MLD and no variants in the ARSA gene (Test #620) and also patients with atypical forms of Gaucher disease (OMIM 610539), Krabbe disease (OMIM 611722), and combined saposin deficiency (OMIM 611721). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PSAP.


Official Gene Symbol OMIM ID
PSAP 176801
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Metachromatic Leukodystrophy Panel


  • Diaz-Font, A., et.al. (2005). "A mutation within the saposin D domain in a Gaucher disease patient with normal glucocerebrosidase activity." Hum Genet 117(2-3): 275-7. PubMed ID: 15856305
  • Gieselmann, V., et.al. (1989). "Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N-glycosylation site." Proc Natl Acad Sci U S A 86(23): 9436-40. PubMed ID: 2574462
  • Kretz, K. A., et.al. (1990). "Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect." Proc Natl Acad Sci U S A 87(7): 2541-4. PubMed ID: 2320574
  • Masters, P. L., et.al. (1964). "Familial Leucodystrophy." Arch Dis Child 39: 345-55. PubMed ID: 14206875
  • Muller, D., et.al. (1969). "Studies on adult metachromatic leukodystrophy. 1. Clinical, morphological and histochemical observations in two cases." J Neurol Sci 9(3): 567-84. PubMed ID: 4189441
  • Schnabel, D., et.al. (1991). "Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease." FEBS Lett 284(1): 57-9. PubMed ID: 2060627
  • Schnabel, D., et.al. (1992). "Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene." J Biol Chem 267(5): 3312-5. PubMed ID: 1371116
  • Schutta, H. S., et.al. (1966). "A family study of the late infantile and juvenile forms of metachromatic leucodystrophy." J Med Genet 3(2): 86-91. PubMed ID: 5963214
  • Spiegel, R., et.al. (2005). "A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans." Mol Genet Metab 84(2): 160-6. PubMed ID: 15773042


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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