IMPE Abstracts

We present a 9 years old girl, L.B, referred to Pediatric Endocrinology due to progressive deformity in lower limbs since 7 years of age. This is a previously healthy child, no neonatal complications and adequate neuromotor development. At 2 years old, a thin hair appearance was noticed. She had a poor daily calcium intajke of 400mg/day and adequate sun exposure. At physical examination, it was noted severe short stature (-3.8 SDS), genus valgus, widening of wrists and ankles, and rachitic rosary. Laboratory profile showed a 46 XX karyotype, normal thyroid and renal function. Regarding to osteometabolic profile, she presented hypophosphataemia with hyperphosphaturia, nocmocalcemia, normagnesemia, hypoparathyroidism, and hyperphosphatasemia. She also had normal 25OH vitamin D and an elevated FGF23. Radiological findings showed diffuse bone rarefaction, cupping, widening and fraying of metaphyseal regions of long bones. Next-generation sequencing analysis was performed, and we found, in heterozygosity, a pathogenic variant in the BCS1L gene (OMIM*603647).

Discussion: Rickets is characterized by a deficiency in the mineralization of the growth plate, leading to its architectural rupture. Hypophosphatemic rickets with hyperphosphaturia can be caused by excess of phosphatonin FGF23. The most common cause of excess FGF23 is a loss-of-function mutation in the PHEX gene. The mutation in the BCS1L gene associated with excess serum FGF23 has not been previously described in the literature. In the literature review, the mutation was described in association with tubulopathy/fanconi syndrome, resulting in rickets. A turkish paper presented individuals with such nephropathies, associated with other manifestations, such as: transient metabolic acidosis in the neonatal period, deafness, microcephaly and mental retardation, not present in our patient. This mutation has also been reported leading to Gracile syndrome and Leigh-like syndrome, which are also inconsistent with the clinical signs of our patient. Thus, we emphasize the importance of molecular investigation of hypophosphatemic rickets cases, in order to better understand the causal relationship between the BCS1L gene mutation and the osteometabolic consequences, still poorly elucidated.