Bone Abstracts

Background: Hypophosphatasia is generally regarded as a disease of bone and teeth. Lack of Tissue Non-Specific Alkaline Phosphatase (TNAP) leads to an accumulation of inorganic pyrophosphate and the Vitamin B6 metabolite pyridoxal 5′-phosphate (PLP), a reduction in pyridoxic acid (PA) and increased PLP/PA ratio. Vitamin B6 deficiency in the brain impairs synthesis of neurotransmitters, and is a well-recognised cause of neonatal seizures. We have found no previous reports of ADEM as a feature of Hypophosphatasia beyond the neonatal period.

Presenting problem: A 12 year old girl with ADEM was noticed to have persistently low serum alkaline phosphatase activity. She had presented to her local hospital with a 1 week history of fever, drowsiness and difficultly walking. She developed increasing weakness, slurred speech and 2 days later respiratory failure requiring ventilation. Brain MRI and EEG showed signs of ADEM. She was born with a malformation of her left hand but never had dental or bone features of hypophosphatasia.

Clinical management: She was treated with intravenous antibiotics, antiviral therapy, steroids and plasmapheresis. It was later noticed that her serum Alkaline Phosphatase activity had been low since presentation (22–37 IU/l). Her plasma PLP was 302 nmol/l (range 20–140) with a PA of 39 nmol/l (9–60) giving a PLP/PA ratio of 8 (normal non-supplemented subjects <5.0) supporting the diagnosis of hypophosphatasia. Genetic analysis showed a pathogenic heterozygous mutation in exon 5 of ALPL: c.346G>A, p.Ala116Thr. Review of her neonatal record, and that of her twin sister, revealed that both girls had low alkaline phosphatase activity on routine blood test at 4 days of age (47 and 58 IU/L respectively). The twin has had no symptoms.

Discussion: TNAP is known to be expressed in the synapses of the cerebral cortex that are involved in neurotransmitter synthesis, synaptic stabilization, and myelin pattern formation. This case raises the possibility that that hypophosphatasia might be causally related to ADEM.

Disclosure: The authors declared no competing interests.