Treatment of Rickets with Arterial or Cardiac Calcification in Autosomal-Recessive Hypophosphatemic Rickets Type 2 (Biallelic ENPP1 Mutations)
Autosomal-recessive hypophosphatemic rickets type 2 (ARHR2) caused by biallelic ENPP1 mutations presents a distinct and clinically demanding variant of hypophosphatemic rickets. When arterial or cardiac calcification is also present, the management approach differs substantially from other forms of the condition.
Clinical Scenario
This protocol applies to patients with confirmed ARHR2 due to biallelic ENPP1 mutations who have evidence of arterial or cardiac calcification. The presence of vascular or cardiac calcification is a critical comorbidity that directly constrains which therapeutic agents can be used safely, requiring a tailored treatment strategy.
Treatment Approach (Partial Overview)
Management centres on phosphate supplementation as the primary intervention. Critically, the presence of arterial or cardiac calcification precludes the use of active vitamin D — a cornerstone of many other hypophosphatemic rickets regimens — making phosphate salts the mainstay of this specific protocol.
Specific dosing, sequencing, and the complete structured regimen are available via the full protocol below.
References
DOI: 10.1007/s00467-022-05505-5
- The latter phenotypes preclude treatment with active vitamin D.
- The presence of calcifications precludes treatment with active vitamin D.
- In a small series including 6 ARHR2 patients, the reported dosages of phosphate salts (based on elemental phosphate) and calcitriol amounted to 40 mg/kg day and 15 ng/kg per day, respectively.