Fibroblast growth factor-23 (FGF23) regulates phosphate reabsorption in the kidney and therefore plays an essential role in phosphate balance in humans. There is a host of defects that ultimately lead to excess FGF23 levels and thereby cause renal phosphate wasting and hypophosphatemic rickets. We describe the genetic, pathophysiologic, and clinical aspects of this group of disorders with a focus on X-linked hypophosphatemia (XLH), the best characterized of these abnormalities. We also discuss autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR) and tumor-induced osteomalacia (TIO) in addition to other rarer FGF23-mediated conditions. We contrast the FGF23-mediated disorders with FGF23-independent hypophosphatemia, specifically hypophosphatemic rickets with hypercalciuria (HHRH). Errant diagnosis of hypophosphatemic disorders is common. This review aims to enhance the recognition and appropriate diagnosis of hypophosphatemia and to guide appropriate treatment.

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Historically, delayed puberty was considered a common clinical feature of cystic fibrosis (CF). More recent reports have documented normal pubertal progression in the majority of individuals with CF. However, youth with more severe disease are still at risk for delayed puberty. Careful evaluation of pubertal development in children and adolescents with CF is important as pubertal timing impacts linear growth, bone mineral accrual, body image and psychosocial wellbeing, all of which can also be impacted directly by CF. This article reviews the physiology of puberty, timing of puberty in CF, evaluation of pubertal development, and the differential diagnosis, evaluation, and management of delayed and precocious puberty in people with CF.

A 2-year-old girl with a history of DiGeorge syndrome (interrupted aortic arch, atrial and ventricular septal defects status post repair, feeding difficulties, developmental delay, vocal cord paralysis, and hypoparathyroidism) presented to the emergency department after 2 days of decreased urine output, gait instability, and lethargy. Her parents reported feeding her a high-calorie diet, rich in butter and cheese, to promote weight gain. In the emergency department, physical examination showed nonreactive pupils, right eye deviation, and tonic upper extremities, consistent with seizure activity. She had bradycardia (pulse 70 bpm) and hypertension (164/125 mm Hg). Laboratory evaluation included a serum sodium concentration of 198 mmol/L, chloride of 167 mmol/L, potassium of 3.5 mmol/L, serum osmolality of 398 mOsm/kg, urine sodium of 235 mmol/L, and urine osmolality of 580 mOsm/kg. Serum calcium was normal.Magnetic resonance imaging of the brain, before treatment of hypernatremia, showed bilateral and symmetric edema with restricted diffusion of the external capsules (Figure, A and B, arrows), anterior limbs of the internal capsules, thalami, and subcortical white matter of the parietal, temporal, and occipital lobes, consistent with extrapontine myelinolysis. No abnormalities were noted in the pons or remainder of the brainstem. There was also focal restricted diffusion of the bilateral hippocampi (Figure, C, arrow heads), and uncinate fasciculi lateral to the amygdala. The hippocampal lesions were similar to those described in prior reports of children with severe hypernatremia and extrapontine myelinolysis. 1,2 The syndrome of osmotic demyelination is due to a process that can occur in the setting of rapid shifts in osmolality and occurs either within the pons (central pontine myelinolysis) or outside the pons (extrapontine myelinolysis). The etiology of this patient's hypernatremia was presumed to be due to salt intoxication, and the extrapontine myelinolysis occurred due to the rapid increase in serum sodium concentration. Hypernatremia was slowly corrected over 4 days, and she remained globally hypotonic and visually inattentive throughout her 2-week hospitalization. She was discharged to an acute rehabilitation facility and slowly improved to her baseline neurologic status. Given her clinical improvement, a convalescent magnetic resonance imaging was not performed. ■ A B C Figure. A, Fluid-attenuated inversion recovery image and B, diffusion-weighted image (DWI) at the same level showing corresponding hyperintensity of the external capsule. C, DWI showing hyperintensity of the hippocampi.