ESPE Abstracts (2019) 92 P3-30

ENPP1 Hypophosphatemic Rickets in a 3.6 Years Old Italian Child

Daniele Tessaris, Enrica Abrigo, Gerdi Tuli, Patrizia Matarazzo, Luisa de Sanctis


Pediatric Endocrinology, University of Torino, Torino, Italy


Introduction: Although vitamin D deficit is the most common cause of rickets there are many rare genetically transmitted forms as hypophosphatemic rickets, a family of hereditary diseases characterized by low phosphorous plasma levels and resistance to 25OH-vitamin D replacement.

Case report: This is the case of a 3.6 year-old Italian child sent from the General Pediatrician, for rickets suspicion. Silent personal history and familiar anamnesis, no history of consanguinity.

The baby was breast-fed until she was 11 month-old and she was regularly supplemented with 25OH-vitamin D for 12 months after birth. Examination: 94.3 cm (25° centile, -1.25 SDS) ; 14.5 kg (25° centile, -0.69 SDS); TH 172 cm (75° centile, ). Presence of rachitic rosary, bracelet and femoral bowing. Biochemical data at presentation: calcium 1.18 mmol / l (n.v. 2-2.6), phosphate 0.84 mmol/ l (n.v 1.1-1.94), alkaline phosphatase 527 U / l (n.v. 150-380), PTH 52.7 pg / ml (n.v 9-65), 25-hydroxyvitamin D 16.7 ng / ml (n.v. >30), RTP 82% (n.v. 80-90). X ray lower limbs: bowing of femur with enlargement and structural irregularities of distal metaphyseal epiphyseal regions; similar features also present at the tibia level. Normocalcemia and normal levels of 25(OH)D (after three months of 25OH-vitamin D supplementation), combined with normal PTH values in presence of hypophosphatemia, suggested vitamin D resistant hypophosphatemic rickets. Although molecular analysis of PHEX gene didn't found any mutations, further genetic investigations have allowed to find two variants in heterozygous in the ENPP1 locus: the translocation c.715+2T>g in exon's 6 splicing site and the deletion c.1437+3_1437+6del4 in intron 14 (ARHR2), responsible for another rare autosomal-recessive form of the disease. The same mutations have been confirmed respectively in mother and father who are healthy genetic carriers.

The child has started treatment with the active vitamin D metabolite, 1,25(OH)2D pills 250 ng: 17.2 ng/kg/day, associated with inorganic phosphorous salts pills 195.6 mg: initial dose 26.9 ng/kg/day divided in 2-3 doses day. During the follow-up, a 2/6 systolic pulse has appeared, associated to a pathological echocardiogram showing calcification at the aortic valve. Moreover she has developed bilateral transmitting hypoacusia, lower limbs pain, fatigue and dental enamel disturbances.

Discussion: With current therapy based on supplementation of phosphate and 1,25(OH)2D complete healing of the osteomalacia and correction of the biochemical abnormalities are generally incomplete. Patients affected by hypophosphatemic rickets need to start a multidisciplinary follow-up including endocrinologist, orthopaedic, odontoiatric and cardiologist specialists.

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