Metachromatic Leukodystrophy via the PSAP Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits


Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
511 PSAP$840.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
Currently not known.

See More

See Less

Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 PSAP$690.00 81479 Add to Order
Pricing Comment

# of Genes Ordered

Total Price













Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 28 days.

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 mutations 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 mutations have been reported. They are distributed along the entire coding region of the gene, and occurred in patients from various ethnic groups. Mutations include missense, nonsense, splicing and small insertions. In addition to MLD, mutations 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).
Testing Strategy
This test involves bidirectional DNA sequencing of all 14 coding exons and splice sites of the PSAP gene. The full coding sequence of each exon plus ~ 20 bp of flanking DNA on either side are sequenced. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.
Indications for Test
Candidates for this test are patients with MLD and no mutations 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).


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

Related Test

Metachromatic Leukodystrophy Sequencing Panel


Genetic Counselors
  • Diaz-Font, A., (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., (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., (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., (1964). "Familial Leucodystrophy." Arch Dis Child 39: 345-55. PubMed ID: 14206875
  • Muller, D., (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., (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., (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., (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., (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
Order Kits

Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
loading Loading... ×