ADH1 Diagnosis and the Importance of Genetic Testing
For effective disease management, it is important to differentiate ADH1 from other forms of hypoparathyroidism.1 Biochemical findings and family history can help establish a diagnosis of ADH1.2-4 Additionally, ADH1 can be confirmed through genetic testing for gain-of-function variants in the CASR gene.1,3
Biochemical Findings
Patients with ADH1 often present with varying degrees of the following1,5:
- Hypocalcemia
- Hypomagnesemia
- Hypercalciuria
- Hyperphosphatemia
- Low PTH levels
While the biochemical profile of patients with ADH1 resembles that of other forms of hypoparathyroidism, patients with ADH1 experience more pronounced hypercalciuria when treated with conventional therapies (activated vitamin D and Ca2+ supplements).1 This is due to the combined effects of low PTH and overly sensitive CaSR in the kidneys, leading to reduced Ca2+ reabsorption from the kidneys and associated complications, such as nephrocalcinosis, nephrolithiasis, and kidney impairment.1,3,6
Family History
ADH1 is primarily inherited in an autosomal-dominant manner. A child has a 50% chance of having ADH1 if they have an affected parent.3 However, approximately 20% of ADH1 cases occur spontaneously (without a family history), so ADH1 should still be considered for patients with a medical history that is consistent with the biochemical features of ADH1.1,4
Confirmatory Genetic Testing
Genetic testing of the CASR gene can help to establish an accurate diagnosis of ADH1.1,3,4 Recent guidelines recommend genetic testing for all nonsurgical patients with hypoparathyroidism who present with at least 1 of the following: younger than 40 years old, family history of nonsurgical hypoparathyroidism, or exhibit syndromic features.3
An accurate diagnosis affects how the disease is managed. Management strategies include tailoring the treatment to each individual, providing appropriate patient support through genetic counseling, family planning, and resources such as patient advocacy organizations, and identifying potential eligibility for participation in clinical trials.1,2,4,7
ICD-10 for ADH1
The International Classification of Diseases, Tenth Revision (ICD-10)
code for ADH1 is E20.810.8
BridgeBio provides this information for your convenience only. It does not constitute legal advice or a recommendation regarding clinical practice. Information provided is gathered from third-party sources and is subject to change without notice due to frequently changing laws, rules, and regulations. The provider has the responsibility to determine medical necessity and to submit appropriate codes and charges for care provided. BridgeBio makes no guarantee that the use of this information will prevent differences of opinion or disputes with Medicare or other payers as to the correct form of billing or the amount that will be paid to providers of services. Please contact your Medicare contractor, other payers, reimbursement specialists and/or legal counsel for interpretation of coding, coverage, and payment policies.
No-Charge Testing Program
BridgeBio is committed to leading the way toward improved diagnosis of ADH1.9
BridgeBio sponsors no-charge genetic testing and counseling programs in the United States for eligible patients and family members suspected of having genetic forms of hypoparathyroidism. Through the partnership between PreventionGenetics and BridgeBio, the DetectHypopara™ program offers healthcare professionals genetic test kits at no charge for eligible patients and their family members.10
For a patient to be eligible, they must reside in the United States or Canada and have 1 of the following diagnoses:
Nonsurgical
hypoparathyroidism
Idiopathic
hypoparathyroidism
Hypocalcemia
suspected to be of
genetic cause
Genetic
hypoparathyroidism
in a relative
This genetic testing program leverages a whole-exome backbone using next-generation sequencing and includes 26 genes known to cause hypoparathyroidism, including CASR, with options to collect whole blood, saliva, or buccal specimens.10
The program also partners with Genome Medical to offer no-charge genetic counseling to support healthcare professionals in helping their patients understand their genetic test results and identifying family members who may also be affected.
How to Order a Test Kit
To order a test kit, please use the link provided below.
Kits are provided at no charge and include prepaid return postage.11
Kits may take up to 1 week for delivery.11
References
1. Roszko KL, Stapleton Smith LM, Sridhar AV, et al. Autosomal dominant hypocalcemia type 1: a systematic review. J Bone Miner Res. 2022;37(10):1926-1935. doi:10.1002/jbmr.4659
2. Khan AA, Bilezikian JP, Brandi ML, et al. Evaluation and management of hypoparathyroidism summary statement and guidelines from the Second International Workshop.
J Bone Miner Res. 2022;37(12):2568-2585. doi:10.1002/jbmr.4691
3. Mannstadt M, Cianferotti L, Gafni RI, et al. Hypoparathyroidism: genetics and
diagnosis. J Bone Miner Res. 2022;37(12):2615-2629. doi:10.1002/jbmr.4667
4. Bilezikian JP, Khan A, Potts JT Jr, et al. Hypoparathyroidism in
the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research.
J Bone Miner Res. 2011;26(10):2317-2337. doi:10.1002/jbmr.483
5. Pearce SH, Williamson C, Kifor O, et al. A familial syndrome of
hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor. N Engl J Med. 1996;335(15):1115-1122.
doi:10.1056/NEJM199610103351505
6. Roszko KL, Bi RD, Mannstadt M. Autosomal dominant hypocalcemia (hypoparathyroidism)
types 1 and 2. Front Physiol. 2016;7:458. doi:10.3389/fphys.2016.00458
7. Bollerslev J, Rejnmark L, Marcocci C, et al. European Society of
Endocrinology clinical guideline: treatment of chronic hypoparathyroidism in adults. Eur J Endocrinol. 2015;173(2):G1-G20. doi:10.1530/EJE-15-0628
8. Centers for Disease Control
and Prevention (CDC). Hypocalcemia. National Center for Health Statistics - ICD-10-CM. Updated April 1, 2024. Accessed July 25, 2024. https://icd10cmtool.cdc.gov/?fy=FY2024&query=ADH1
9. BridgeBio.
What is autosomal dominant hypocalcemia type 1. Accessed July 25, 2024. https://bridgebio.com/what-is-adh1 #:~:text=ICD-10%20code%20for%20autosomal%20dominant%20hypocalcemia%E2%80%8B%20Code%20E20.8,autosomal%20dominant%20hypocalcemia%20type%201%20or%20type%202
10. Prevention Genetics. Calcilytix DetectHypopara. Accessed October 9, 2024. https://www.preventiongenetics.com/sponsoredTesting/Calcilytix_DetectHypopara
11. Prevention Genetics. Calcilytix. Detect Hypopara kit ordering form. Accessed August 8, 2024. https://www.preventiongenetics.com/calcilytix_detecthypopara