Hypoparathyroidism Sponsored Testing Program

Program Overview

In partnership with Calcilytix Therapeutics (a BridgeBio Company), this Hypoparathyroidism Genetic Testing program provides US physicians with access to no-cost genetic testing for patients, who have a clinical diagnosis of non-surgical hypoparathyroidism or hypocalcemia suspected to be of genetic cause, or meet other eligibility criteria for testing. This program was created to learn more about the genetic causes of hypoparathyroidism and support clinical management so that individuals and their providers can make more informed decisions about their health.

Clinical Features

Hypoparathyroidism occurs when the parathyroid glands produce inadequate amounts of parathyroid hormone (PTH) to maintain normal blood calcium levels and may be characterized by hypocalcemia, hyperphosphatemia, and hypomagnesemia (Clarke et al. 2016). Patients with hypoparathyroidism may present with fatigue, muscle spasms, pain, paresthesias, cognitive symptoms such as "brain fog" and inability to concentrate, emotional difficulties including depression and/or anxiety, which suggest impaired quality of life. Patients with hypoparathyroidism have an increased risk of hypocalcemic seizures and calcification of the basal ganglia (Shoback et al. 2016). Hypoparathyroidism is most frequently caused by damage or removal of the parathyroid glands from a surgical procedure and the remaining cases, due to genetic, autoimmune, and other rare etiologies (Mannstadt et al. 2022). A positive family history of non-surgical hypoparathyroidism can be a strong indicator of a genetic disorder, however, pathogenic variants can occur de novo or spontaneously.

Genetics

Genetic forms of hypoparathyroidism include disorders of parathyroid gland formation, parathyroid hormone secretion, and parathyroid gland damage (Mannstadt et al. 2022). Disorders of parathyroid gland formation can be inherited in an autosomal dominant (TBX1, NEBL, SEMAE3, CHD7, GATA3, FAM111A, GCM2), autosomal recessive (TBCE, HADHA, HADHB, ACADM, DHCR7, GCM2), or X-linked manner (SOX3). Disorders of parathyroid hormone secretion can be inherited in an autosomal dominant (CASR, GNA11, PTH, FXYD2, CNNM2, ATP1A1, KCNA1) or autosomal recessive manner (PTH, TRPM6, CLDN16, EGF, CLDN19, CNNM2, SLC12A3). Disorders consisting of parathyroid gland damage can be inherited in an autosomal dominant or autosomal recessive manner.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary. This panel provides 99.6% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Criteria For Test

The patient must reside in the US and meet any one of the following criteria:

  • Has a diagnosis of non-surgical hypoparathyroidism
  • Has a diagnosis of idiopathic hypoparathyroidism
  • Has a diagnosis of hypocalcemia suspected to be of genetic cause
  • Has a relative with a diagnosis of genetic hypoparathyroidism

Ordering

  1. Determine if the individual meets eligibility criteria and discuss the test.
  2. Order the test using the test requisition form.
  3. Collect a specimen in the collection tube. For information on ordering specimen kits, see Specimen Collection and Shipping section.
  4. The genetic test will be processed at PreventionGenetics and the results will be sent to the ordering healthcare provider about 18 days after the lab receives the specimens and all appropriately completed paperwork. The ordering healthcare provider will discuss the results with the patient and/or caregiver.

Genetic Counseling

Individuals tested through this program are eligible for post-test genetic counseling to help them understand their test results. This service is provided through GeneMatters, a third-party genetic counseling service, and is made available by Calcilytix at no-charge as part of the program.

Patients can access genetic counseling by having their healthcare provider:

  • Request pre- and/or post-test genetic counseling from GeneMatters by completing and faxing the Genetic Counseling Referral Form.
  • Or by completing the post-test genetic counseling section of the PreventionGenetics test requisition form.

Patients will be contacted via phone by GeneMatters to schedule an appointment, generally within 24-48 hours of receipt of the faxed referral form.

Specimen Collection and Shipping

SPECIMEN REQUIREMENTS

Whole Blood

Collect 3 ml - 5 ml of whole blood in EDTA (purple top tube) or ACD (yellow top tube), minimum 1 ml for small infants. Heparin (green top tube) is strongly discouraged.

Saliva

Oragene™ or GeneFiX™ Saliva Collection kit used according to manufacturer instructions. DNA from saliva specimens is invariably contaminated with microbial and food DNA, which can impact specimen quality and may result in delayed testing and/or the need for a second specimen.

OCD-100 Buccal Swab

OCD-100 Buccal Swab used according to manufacturer instructions.

Buccal

Specimens may be shipped at room temperature.

Specimen collection kits: Buccal specimen collection kits, which contain the TRF and the shipping label, may be requested through the kit order form or via the online order form.

SHIPPING AND HANDLING INSTRUCTIONS

Label all specimen containers with the patient's name, date of birth, and/or ID number. At least two identifiers should be listed on specimen containers. Specimen deliveries are accepted Monday-Saturday for all specimen types. Holiday schedules will be posted on our website at least one week prior to major holidays.