A 7.7 year old girl born to consanguineous was assessed for poor growth; height −3.2 SDS, weight −2.7 SDS, BMI −0.8 SDS. Examination revealed chubby cheeks, abdominal obesity, relatively thin limbs and a suggestion of mid-face hypoplasia. There was no scoliosis or other dysmorphic features.
Investigations found a 46XX karyotype and negative coeliac screen. Pituitary function testing revealed high basal Growth Hormone (GH) of 6.5 ug/l, rising to 25.5 ug/l, but with undetectable IGF-1 (<3.2). An IGF-I generation test performed following 4 days of GH (0.035 mg/kg/day) displayed no increment in IGF-I. DNA analysis for a GHR mutation was negative. In tandem she was also investigated for a microcytic anaemia (Hb 113 g/l), neutropenia (1.4) and a raised LDH 1070 (160430) and ferritin 898 (10322). A bone marrow aspirate was normal. Metabolic investigations showed a pattern of amino acids consistent with lysinuric protein intolerance (LPI).
LPI is a rare autosomal recessive metabolic disorder affecting amino acid transport. The condition typically presents after an infant is weaned, with recurrent diarrhoea and vomiting especially following protein rich meals. It may have a multisystem clinical presentation including growth, haematological abnormalities and rarely osteoporosis. The diagnosis is based on biochemical findings, including increased urine concentrations of lysine, arginine and ornithine but with low concentrations in the plasma. Molecular testing identifies two SLC7A7 pathogenic variants in more than 95% of individuals. Treatment includes citrulline and a low protein diet.
As LPI may be associated with osteoporosis, the bone health was further investigated. The Bone density Z-scores were −5.0 & −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 tenderness on palpation. Treatment with intravenous bisphosphonatese improved the bone pain.
Although low GH levels have been reported in LPI, IGF-I deficiency with high GH has not been described. Furthermore, osteoporosis is 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.
23 - 25 Nov 2016
British Society for Paediatric Endocrinology and Diabetes