Hypophosphatasia may lead to bone fragility: don’t miss it

Abstract

Hypophosphatasia is an inheritable disorder characterised by defective bone mineralisation due to the impaired activity of tissue-non-specific alkaline phosphatase (AP). Clinical presentation ranges from stillbirth without mineralised bone to pathological fractures in late adulthood. During childhood, the main manifestations include rickets, growth delay and dental problems. Fractures and bone pain usually characterise the adult form. A 9-year-old girl was referred for repetitive fractures after minimal trauma. She had normal growth, normal sclerae, no rickets and minimal dental abnormalities. Her sister had also presented fractures. The proband, her sister and mother had low total and bone-specific AP levels and E435K mutation in exon 12 of the liver/bone/kidney AP gene. Low AP levels must lead to genetic analysis. Bone fragility and repetitive fractures may be symptoms of hypophosphatasia in childhood, which must not be neglected. Associated factors such as vitamin D or calcium deficiency must be prevented. In conclusion, hypophosphatasia must not be forgotten as an aetiological factor of repetitive fractures or bone pain in children and AP activity should be checked accurately.

Hypophosphatasia: an overview of the disease and its treatment

“…Her sister had also had fractures. Low total ALP and bone-specific ALP were thereafter discovered in both girls and their mother, and an ALPL gene mutation (E435K) was identified [67].…”

Clinical utility gene card for: Hypophosphatasia – update 2013

“…36 Especially, for children with persistent growth retardation, an aedequate nutrition with the support of a professional dietician is of major importance. 37 Supplementation with vitamin D can be recommended according to the guidelines for healthy children. Further, additional vitamin D therapy, as it is used in vitamin D-deficient rickets, should be avoided.…”

Hypophosphatasia: Review of Bone Mineral Metabolism, Pathophysiology, Clinical Presentation, Diagnosis, and Treatment

“…Radiography displays beading of the costochondral junction, bony defects projecting from growth plates to metaphyses termed Btongues^of radiolucency, metaphyseal flaring leading to joint enlargement, an elongated skull with a Bbeaten-copperâ ppearance due to closure of cranial sutures, and rarely bone marrow edema [1,35]. Children may also display scoliosis or recurrent fractures [74,81]. This form is not typically associated with pyridoxine-responsive seizures.…”