Endocrine Abstracts

Hypophosphatasia (HPP) is a rare inherited disorder caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. HPP B is a multisystemic B disorder with a predominantly B skeletal phenotype, with a clinical spectrum ranging from high lethality in early onset (<6 months) HPP to mild late-onset presentations. HPP skeletal disease in utero was thought to predict a lethal outcome. However a benign prenatal form (PB HPP) with a mild postnatal course has been emphasized in several reports. We report the case of a girl born full term with absent parietal bones, severe deficits in temporal and occipital bones and widely separated frontal and lambdoid sutures. There was also absence of the nasal bone and severe hypoplasia of the clavicles. No respiratory support was required. The laboratory investigation revealed low levels of ALP (44 U/L- 77 U/L, ref. range 115–460 U/L) with normal levels of calcium and phosphorus in blood and urine, normal serum magnesium, PTH and 25(OH) D levels. The TNSALP gene was analyzed by PCR and direct sequencing. A heterozygous TNSALP variant c.542C>T was detected, which has been predicted as pathogenic and has been identified in compound heterozygosity in two cases of infantile HPP and in heterozygosity in a patient with adultHPP. On re-evaluation 6 months later, there is no improvement of her bone deficits, with persistently low alkaline phosphatase and calcium levels at the upper normal range. In light of this clinical course, Asfotase alfa has been considered as a possible treatment due to the persistence of extended skull deficits.