Bone Abstracts

Background: Hyperphosphatasia may be seen in liver disorders or metabolic bone disease with the most common cause likely to be Vitamin D deficiency. However, we report the case of child who had high ALP levels from infancy along with intellectual retardation. Genetic testing revealed Mabry Syndrome.

Presenting problem: At birth, a micrognanthia and a cleft palate was apparent. She went to have developmental delay, impaired vision, and was wheelchair dependent. She had a working diagnosis of Pierre Robin Sequence. There was no bone pain, spinal tenderness or any fracture history. There was adequate calcium in her diet.

Results: The ALP was elevated from birth with levels persistently around 2000iu/L (100-400). The calcium and phosphate were always normal, the Vitamin D levels were often very low (<20 nmol/L), with a PTH level either in the normal or just above the normal range. She had regular treatment with Vitamin D, including an intramuscular injection. Bone specific ALP was markedly raised, but this test coincided with severe Vitamin D deficiency. A skeletal survey was taken at 8 years of age. Apart from a scoliosis, it did not show any skeletal dysplasia or features of juvenile Paget’s disease. She had a further opinion at 9 years of age and a diagnosis of Mabry syndrome was considered. Genetic Testing showed she was homozygous for the pathogenic PGAP3 mutation c182-2A>G which is known to cause hyperphosphatasia with mental retardation syndrome 4 (HPMRS4).

Discussion: Mabry syndrome is a rare autosomal recessive condition caused by an impairment of glycosylphophatidylinositol biosynthesis resulting in high ALP levels. It is characterized by elevated serum alkaline phosphatase, severe psychomotor developmental delay, seizures, and facial dysmorphism. Fractures, camptodactyly, truncal obesity, and hyperpigmented macules have been described. In patients with persistent unexplained hyperphosphatasia and mental retardation, genetic testing for Mabry syndrome should be considered.

Disclosure: The authors declared no competing interests.