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Hypophosphatasia via the ALPL 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
ALPL 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7573ALPL81479 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


  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Hypophosphatasia (HPP) is characterized by defective mineralization of bone or teeth in the presence of low activity of serum and bone alkaline phosphatase. Clinical features range from stillbirth without mineralized bone at the severe end to pathologic fractures of the lower extremities in later adulthood at the mild end. At least six clinical forms are currently recognized based on age at diagnosis and severity of features, including: (1) perinatal lethal HPP characterized by respiratory insufficiency and hypercalcemia; (2) perinatal benign HPP with prenatal skeletal manifestations that slowly resolve into the milder childhood or adult form; (3) infantile HPP (OMIM#241500) with onset between birth and six months characterized by rickets without elevated serum alkaline phosphatase activity; (4) childhood HPP (OMIM#241510) that ranges from low bone mineral density for age with unexplained fractures to rickets; (5) adult HPP (OMIM#146300) characterized by early loss of adult dentition and stress fractures and pseudofractures of the lower extremities in middle age; and (6) odontohypophosphatasia characterized by premature exfoliation of primary teeth or severe dental caries as an isolated finding or as part of the above forms of HPP (Mornet & Nunes. GeneReviews. 2010).


ALPL is the only gene known to be associated with HPP. ALPL encodes alkaline phosphatase, tissue-nonspecific isozyme (TNSALP), which is present in liver, kidney, and bone. Perinatal and infantile HPP are inherited in an autosomal recessive manner. The milder forms, especially adult and odontohypophosphatasia, may be inherited in an autosomal recessive or dominant manner depending on the effect that the variant has on TNSALP activity. In recessive HPP, heterozygotes either are asymptomatic, manifesting biochemical but not clinical abnormality, or may manifest milder symptoms depending on the variant. A good correlation exists between the severity of the phenotype and the residual enzymatic activity (Zurutuza et al. Hum Mol Genet 8:1039–1046, 1999; Orimo et al. J Bone Miner Res 16:2313–2319, 2001). A variety of variants in ALPL have been reported with the majority being missense changes.

Clinical Sensitivity - Sequencing with CNV PG-Select

Sequencing of ALPL is predicted to detect disease variants in 95% of cases with severe perinatal and infantile HPP. In milder forms, variant detection rate is difficult to estimate. Overall, ~50% of cases with a clinical diagnosis of HPP have two ALPL variants and ~40%-45% have one variant. The milder the disease, the higher the proportion in which only one ALPL variant is detected (Mornet & Nunes GeneReviews 2010).

Testing Strategy

This test provides full coverage of all coding exons of the ALPL 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 clinical features consistent with HPP or biochemical abnormality showing reduced activity of serum alkaline phosphatase (ALP) or elevated urine phosphoethanolamine (PEA) and family members of patients who have known ALPL variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ALPL.


Official Gene Symbol OMIM ID
ALPL 171760
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Etienne Mornet (2010). "Hypophosphatasia."
  • Orimo, H., et.al. (2001). "Mutational analysis and functional correlation with phenotype in German patients with childhood-type hypophosphatasia." J Bone Miner Res 16(12): 2313-9. PubMed ID: 11760847
  • Zurutuza, L., et.al. (1999). "Correlations of genotype and phenotype in hypophosphatasia." Hum Mol Genet 8(6): 1039-46. PubMed ID: 10332035


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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View Ordering Instructions

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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