Diagnostic Delay

Patients with ADH1 can be difficult to identify based on symptoms alone and often face a prolonged delay in achieving a complete diagnosis.¹ Some people with ADH1 may receive an incomplete diagnosis (eg, idiopathic hypoparathyroidism or hypocalcemia) or a misdiagnosis (eg, seizure-, respiratory- or cardiovascular-related disorders), or never learn of the underlying genetic cause of their condition.¹ While symptoms may start in infancy, patients with ADH1 may not receive an accurate diagnosis until they are adults.² Although the median age of diagnosis of a hypocalcemia-related disorder is 4, according to a systematic literature review, the median age for a genetically confirmed diagnosis of ADH1 is 25 years.¹

Accurate diagnosis of ADH1 is necessary to optimize disease management and monitoring, as treatment-emergent complications occur in 75% of patients.¹ Genetic testing is required to confirm an ADH1 diagnosis.^2,3 Early detection has the potential to improve disease management for both short- and long-term consequences of the disease.^1,4,5

Disease Manifestation and
Impact on Patients

Most patients with ADH1 experience hypocalcemia, which can result in muscle cramps and spasms and, in some cases, seizures, laryngospasms, and heart rhythm disorders.¹

As a result of prolonged conventional treatment with calcium supplements and vitamin D analogues, kidney calcification (nephrocalcinosis), kidney stones (nephrolithiasis), and kidney failure have been noted in some patients.^1,6

In addition to physical symptoms, patients with hypoparathyroidism, including ADH1, often experience fatigue, depression, cognitive impairment, and anxiety, which can significantly impact their psychological well-being and everyday life.^4,5 It can be challenging for patients with hypoparathyroidism, including ADH1, to conduct their daily routines and maintain personal and work relationships.⁴

Current Disease Management
and Unmet Needs

Currently, the main goal in managing ADH1 with conventional therapy is to keep blood calcium levels close to, or slightly below, the lower limit of normal.^1,6,7 Keeping overall calcium levels low is required to avoid hypercalciuria and associated renal complications.^1,6,7

Currently, there are no medications specifically indicated to treat ADH1.¹ Conventional therapies including calcium supplements and activated vitamin D may provide symptomatic relief and may worsen hypercalciuria, which increases the risk of long-term renal complications, such as kidney stones, calcification, and impairment.^1,8 There remains a substantial unmet need for tailored, efficacious, and well-tolerated therapies that address the underlying molecular mechanism of ADH1.^1,7