Context: Type 1A pseudohypoparathyroidism (PHP-1A) is characterized by target organ resistance to PTH and Albrights hereditary osteodystrophy (AHO). Basal ganglia calcifications and subcutaneous ossifications can be seen in PHP-1A. Acetazolamide, a carbonic anhydrase inhibitor, causes metabolic acidosis by increasing bicarbonate excretion from the proximal renal tubule thereby diminish precipitation of calcium and phosphorus. Acetazolamide had been used for soft tissue calcifications in tumoral calcinosis cases, however not used in PHP-1A and vascular calcification previously. Here, we report the beneficial effect of acetazolamide treatment in a PHP-1A patient with the subcutaneous and intravascular calcifications.
Case Description: A female patient presented with short stature, fatigue and exercise-induced carpopedal spasms at the age of 117/12 years. Diagnosis of PHP-1A was made based on hypocalcemia, hyperphosphatemia, elevated serum PTH and AHO features (Round face, short stature, short metacarpal bones) and calcifications in the basal ganglia). Her height was 127.6 cm (-3.37 SDS), weight was 30 kg (-1.81 SDS). The patient was treated with IV and oral calcium and calcitriol. During intravenous calcium therapy, extravasation of calcium occurred in left forearm and a small hematoma developed in the right antecubital area after phlebotomy. Three weeks later on follow-up examination, a palpable rigidity was detected along the extravasated vascular path on the left arm and a 2x1 cm solid nodule was palpable in the location of hematoma in the right antecubital area. X-ray of the arms demonstrated calcification in these areas. Venous doppler ultrasound examination was consistent with thrombophlebitis and intravascular calcifications in both arms. The patient was treated with antibiotics and low molecular weight heparin (LMWH) for thrombophlebitis. Acetazolamide (25 mg/kg/day) was started for calcifications which created mild metabolic acidosis (pH: 7.30-7.35). LMWH was discontinued on 6 months and acetazolamide treatment was discontinued at 8 months of treatment when calcifications in both arms disappeared completely. No adverse effects were observed during treatment. Maternally inherited p.Arg999Thrfs*47 heterozygous mutation was detected in the GNAS gene.
Conclusions: This case represents the first successful use of Acetazolamide for soft tissue and vascular calcifications in PHP and provides new insight for treatment of ectopic calcifications in PHP.
22 Sep 2021 - 26 Sep 2021