Introduction: Propionic Acidaemia (PA), an organic acidaemia, is characterized by episodes of decompensation with severe metabolic acidosis and hyperammonaemia. PA is associated with low bone mineral density and osteoporosis. Hypocalcaemia is known to occur in 35-65% of decompensations, however the underlying pathophysiology remains unclear. PTH resistance has previously only been described in one case of hypocalcaemia in PA and we report the first use of alfacalcidol in the management of this complication.
Case: A term female infant presented on day 3 with grunting, acidosis and hyperammonaemia, with subsequent diagnosis of PA. She was hypocalcaemic (1.32mmol/L) with a profile suggestive of PTH resistance: normal phosphate 1.8mmol/L and magnesium 0.78mmol/L, low alkaline phosphatase (ALP),77IU/L, and high parathyroid hormone (PTH) 115ng/L. Vitamin D was low 29nmol/L, but disproportional to the degree of hypocalcaemia. Serum calcium normalized with intravenous calcium and oral cholecalciferol.
At 2.5 months, she decompensated secondary to an infection with vomiting, lethargy and jitteriness. Bloods showed acidosis, hyperammonaemia, and hypocalcaemia (1.56mmol/L) with associated PTH resistance: normal vitamin D 91nmol/L, phosphate 1.6mmol/L, magnesium 0.68mmol/L, and ALP 227IU/L, elevated PTH 297ng/L and urine calcium:creatinine ratio 2.75, and low urinary phosphate <1.1mmol/L.
She was managed on intravenous fluids and ammonia scavenger drugs with feeds restarted on day 2. Calcium normalised after treatment with oral calcium (1.25mmol/kg/day), cholecalciferol (3000 units/day) and a magnesium infusion.
Alfacalcidol was started (30ng/kg/day), and oral calcium and cholecalciferol was reduced. Calcium fell (2.5 to 2.01mmol/L) after cessation of calcium supplements, but normalized rapidly (2.56mmol/L) after alfacalcidol was increased to 60ng/kg/day.
Discussion: PTH resistance appears to be the mechanism for hypocalcaemia during episodes of PA decompensation. Acute management of PTH resistance includes active vitamin D (calcitriol or alfacalcidol) and adequate calcium supplementation.
A retrospective chart review of our unit showed that 4 of 6 children had hypocalcaemic episodes (range 1.19-2.01mmol/L) associated with PA decompensation. Out of a total of 25 episodes of decompensation, 9 were associated with hypocalcaemia with normal/slightly low phosphate and ALP. No hypocalcaemia was recorded when patients were well, however routine monitoring was not undertaken. Only in our case was PTH measured and treated with alfacalcidol.
We propose that intermittent PTH resistance may contribute to bone demineralisation in PA. Further studies assessing the mechanism of this and potential utility of ongoing treatment with alfacalcidol would be valuable in guiding long-term management of bone health in PA.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology