1.
Nutritional hypophosphatemic rickets secondary to Neocate® use.
Akhtar Ali, S, Mathalikunnel, A, Bhardwaj, V, Braskett, M, Pitukcheewanont, P
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(9):1887-1891
Abstract
Elemental formula is commonly used in children with feeding intolerance. We describe two, medically complex and feeding tube dependent, patients exclusively fed with Neocate® who subsequently developed hypophosphatemic rickets. Both patients had gross motor decline and pain with physical touch. They were found to have low serum phosphorus, normal calcium, and vitamin D studies, with elevated alkaline phosphatase suggestive of nutritional hypophosphatemia. Both courses were complicated by hypocalcemia following formula change and phosphorus supplementation, highlighting the need for careful management of phosphate repletion in affected individuals. Diligent serial electrolyte monitoring as well as attention to bone health is needed in conjunction with elemental nutrition. Formula change led to restoration of calcium and phosphorus homeostasis and radiographic improvement in these patients.
2.
Unexplained case of hypophosphataemic rickets.
Godden, B, Hilditch, C, Agrawal, R
Journal of paediatrics and child health. 2019;(7):851-853
3.
Triple therapy with pyridoxine, arginine supplementation and dietary lysine restriction in pyridoxine-dependent epilepsy: Neurodevelopmental outcome.
Coughlin, CR, van Karnebeek, CD, Al-Hertani, W, Shuen, AY, Jaggumantri, S, Jack, RM, Gaughan, S, Burns, C, Mirsky, DM, Gallagher, RC, et al
Molecular genetics and metabolism. 2015;(1-2):35-43
Abstract
Pyridoxine-dependent epilepsy (PDE) is an epileptic encephalopathy characterized by response to pharmacologic doses of pyridoxine. PDE is caused by deficiency of α-aminoadipic semialdehyde dehydrogenase resulting in impaired lysine degradation and subsequent accumulation of α-aminoadipic semialdehyde. Despite adequate seizure control with pyridoxine monotherapy, 75% of individuals with PDE have significant developmental delay and intellectual disability. We describe a new combined therapeutic approach to reduce putative toxic metabolites from impaired lysine metabolism. This approach utilizes pyridoxine, a lysine-restricted diet to limit the substrate that leads to neurotoxic metabolite accumulation and L-arginine to compete for brain lysine influx and liver mitochondrial import. We report the developmental and biochemical outcome of six subjects who were treated with this triple therapy. Triple therapy reduced CSF, plasma, and urine biomarkers associated with neurotoxicity in PDE. The addition of arginine supplementation to children already treated with dietary lysine restriction and pyridoxine further reduced toxic metabolites, and in some subjects appeared to improve neurodevelopmental outcome. Dietary lysine restriction was associated with improved seizure control in one subject, and the addition of arginine supplementation increased the objective motor outcome scale in two twin siblings, illustrating the contribution of each component of this treatment combination. Optimal results were noted in the individual treated with triple therapy early in the course of the disease. Residual disease symptoms could be related to early injury suggested by initial MR imaging prior to initiation of treatment or from severe epilepsy prior to diagnosis. This observational study reports the use of triple therapy, which combines three effective components in this rare condition, and suggests that early diagnosis and treatment with this new triple therapy may ameliorate the cognitive impairment in PDE.