ESPE Abstracts

Background: Hypophosphatasia (HPP) is inherited in an autosomal recessive fashion, although symptoms in heterozygous carriers are described. Age at symptom onset determines six clinical forms with different severity and prognosis, but showing phenotypic overlapping.

Objective: We aimed to show this genetic and clinical variability by analyzing two cases.

Case 1: Male, born at 38+5 weeks with 2250 g (−2.22 SDS) and 45 cm (−2.60 SDS), without familial bone disease background. Started rachitic chest deformity at 4 months, left coronal craniosynostosis at 10 months. At 17 months (73.9 cm (−2.65 SDS); 8.4 kg (−2.43 SDS); head circumference: 49 cm (+2 SDS height-adjusted)), he added axial hypotonia (not standing), dolychocephaly, delayed tooth eruption and distal metaphyseal widening in the forearms, with radiological flaring. Repeatedly minimal alkalyne phosphatase (ALP) serum activity (23–31 U/l), with high serum pirydoxal phosphate (PLP >300 mcg/l) and urine phosphoethanolamine (PEA 1395 mmol/mol Creat) were the only abnormal analytical findings. He showed compound heterozygosity (c.542C>T (p.S181L)/c.644T>C (p.I215T)) for ALPL (infantile HPP). At 4.5 years hypotonia, growth impairment (weight −3.00 SDS and height −3.80 SDS); chest deformity (involving functional impairment (forced-vital.capacity 54.2%)), skeletal and tooth impairment (precocious teeth decay, typically described in juvenile HPP) had worsened; determining a typical gait pattern (video and movement analysis study available to display), initiating treatment on recombinant ALP (phase-II clinical trial).

Case 2: A 9-month-old female, born full-term with suitable anthropometry, exclusively showing moderately low ALP serum activity (72–100 U/l) without bone deformities (lacking tooth eruption). Serum PLP was >300 μg/l, and she was heterozygous for the deletion c.217-219delCTC (p.L73del) in ALPL. Her mother (also carrying the deletion) complained from muscle fatigue and pain after long walk (typical symptom in adult HPP).

Conclusion: HPP shows a wide and overlapping clinical phenotype, with variable genotype-phenotype correlation. PLP serum level quantification upon reduced ALP activity allows for the suspicion of HPP in patients with suggestive symptoms.