Bone Abstracts

Background: Lysinuric Protein Intolerance (LPI) is a rare autosomal recessive metabolic disorder affecting amino acid transport. The condition typically presents at weaning, with recurrent diarrhoea and vomiting especially following protein rich meals. It may have a multisystem clinical presentation including growth and haematological abnormalities and rarely osteoporosis. The diagnosis is based on biochemical findings, including increased urine and reduced plasma concentrations of lysine, arginine and ornithine.

Presenting problem: A 7.7 year old girl born to consanguineous parents presented with poor growth; height −3.2 SDS, weight −2.7 SDS, BMI −0.8 SDS. Examination revealed abdominal obesity, thin limbs and a suggestion of mid-face hypoplasia. There was no scoliosis or other dysmorphic features, but a history of recurrent fractures. Investigations showed a 46XX karyotype and negative coeliac screen negative. Pituitary function testing revealed high basal GH of 6.5 μg/l, rising to 25.5 μg/l, but with undetectable IGF-1 (<3.2). An IGF-I generation test performed following 4 days of GH (0.035 mg/kg per day) displayed no increment in IGF-I. DNA analysis for a GHR mutation was negative. Metabolic investigations showed a pattern of amino acids consistent with LPI.

Clinical management: The patient was diagnosed with LPI and commenced on oral citrulline and a low protein diet. Due to the history of fractures and the association between LPI and osteoporosis, the bone health was further investigated. The bone density Z-scores were −5.0 and −3.1 SDS at the Lumbar Spine (Bone Mineral Apparent Density) and total body respectively. A spine X-ray revealed multiple vertebral crush fractures associated with spinal tenderness. Treatment with intravenous pamidronate improved the bone pain significantly. Despite compliance with treatment, our patient’s growth remained poor (height −4.0 SDS) and the IGF-I remained low. She was therefore commenced on recombinant IGF-1 therapy at 9.9 years of age.

Discussion: Although low GH levels have been reported in LPI, IGF-I deficiency with high GH has not been described. Furthermore, osteoporosis is a rare presentation of LPI. In the investigation of growth abnormalities or recurrent fractures in childhood, an index of suspicion should be maintained in the presence of prevailing clinical or biochemical findings and LPI should be considered.

Disclosure: The authors declared no competing interests.