Background: Infantile Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low serum alkaline phosphatase activity caused by loss-of-function mutations within the ALPL-gene encoding the tissue nonspecific isoenzyme of ALP (TNSALP). TNSALP controls skeletal and dental mineralization by hydrolyzing inorganic pyrophosphate, a potent inhibitor of bone mineralization. Patients develop substantial skeletal disease, failure to thrive, and sometimes vitamin B6dependent seizures before 6 months of age. Without treatment, HPP results in 50100% mortality, typically from respiratory complications.
Presenting Problem: We present a 3 months old girl with infantile HPP caused by 2 heterozygous mutations in the ALPL gene. At the age of six weeks she presented with a lack of weight gain because of vomiting and respiratory insufficiency. Clinical investigations showed rhizomelia of the upper arms and femora, short stature, broad nose bridge, high forehead, a bulged fontanelle and muscular hypotension. A single cerebral seizure terminated spontaneously. Laboratory examinations revealed a very low serum ALP activity and a high urinary excretion of phosphoethanolamine. Radiographic findings include hypomineralization with cup-shaped distensions of the metaphysis and irregular zones of ossification.
Clinical Management: Starting enzyme replacement treatment 2 mg/kg s.c. every other day was associated by a supportive therapy with oxygen, enteral nutrition through nasogastric tube, physiotherapy and supplementation of calcium, pyridoxine and analgetics. As a result of therapy x-rays showed an increase of bone mineralization. Stabilization of the chest wall led to a normal breathing pattern without need of oxygen support after 8 weeks. After improvement of vomiting tube-feeding could be weaned after 4 weeks with good weight gain. Muscular strength and neurological function improved also.
Discussion: Infantile hypophosphatasia is extremely rare and may be life threatening.
Our case demonstrates that treatment with the recombinant enzyme therapy led to an improvement in muscular hypotonia, neurological problems and skeletal mineralization and therefore, respiratory function, growth and weight normalised.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology