Hypophosphatasia: The Disease in Adults

Abstract

Hypophosphatasia is an inherited skeletal disorder due to mutations within the ALPL gene that encodes the “tissue-nonspecific isoenzyme of alkaline phosphatase”. This disease is characterized by a low serum alkaline phosphatase. If the severe paediatric forms are quite rare (<1/100,000 births), the prevalence of moderate form is theoretically estimated at 1/6,370, suggesting some unrecognized cases. This condition is inherited in an autosomal recessive manner for a majority of cases, but some moderate adult phenotypes and odonto-hypophosphatasia are autosomal dominant. In adult, the presentation is highly variable, being either manifestations of HPP diagnosed in paediatric age or adult-onset HPP. Adult HPP typically manifests during middle age, as variable osteoarticular pain and recurrent slowly healing fractures of metatarsal bone and proximal femur. The presence of chondrocalcinosis and ectopic calcifications around joints and tendon attachments to bone are also reported. Biochemically, this disease is characterized by an excessive urinary excretion of phosphoethanolamine and elevated serum pyridoxical 5’-phosphate. Elevated serum calcium and phosphorus may be found. The molecular diagnosis is today easily performed, by ALPL gene analysis. Adult patients have to be referred in consultation with a genetics professional, to discuss the related genetic counselling issues with the potential risks to offspring, and depending on the individual case, the possibility of prenatal diagnosis. There is no curative treatment, but symptomatic treatments such as non-steroidal anti-inflammatory agents and teriparatide may improve the symptoms. Enzyme replacement therapy is currently evaluated in phase II clinical trials in children and infants and will, hopefully, be soon discussed in some adults presenting with a significant and progressive disease.