Introduction: Hypophosphatasia is a very rare inherited condition due to ALPL variants and is associated with a variable presentation.
Case description: The index case initially presented at 7 months with bulging anterior fontanelle, failure to thrive and mild developmental delay. She was born at 34 weeks gestation and had amniotic bands causing digital anomalies. She was sitting at 8 months, crawling by 15 months and a hearing test was normal. An MRI head following her initial presentation revealed craniosynostosis and further investigations confirmed intracranial hypertension (ICH), which led to posterior cranial vault distraction at 10 months. Despite this, repeated intracranial pressure monitoring demonstrated persistence of ICH. Of note, preoperative respiratory testing was normal. At 13 months, she had premature loss of 2 deciduous teeth with intact roots and her mother, who is a dental healthcare worker, raised concerns about a bone disorder. Osteopenia and metaphyseal flaring were evident on a left foot and chest X-ray at 4 months and 17 months respectively. At first presentation to the endocrine service at 16 months, her parents also reported possible arm and wrist pain. Other features on examination included a pectus carinatum, prominent eyes, square face and mild rhizomelia. She was also noted to have a persistent pupillary membrane and distended optic nerve sheaths. A micronutrient screen and metabolic and urinary bone screen, including vitamin D and PTH, were normal. However, she had persistently low ALP levels in the range of 2967 U/l (>100). PLP was markedly raised at 1168 nmol/l (20140), PLP/PA ratio was 22.9 and pyridoxic acid result was 51 nmol/l (960), confirming the diagnosis of hypophosphatasia. Genetic testing of 9 craniosynostosis variants was negative and ALPL analysis results are awaited.
Discussion: This case highlights the difficulties in diagnosing infantile hypophosphatasia and the need for maintaining a high index of suspicion and low threshold for detailed investigations.