Table 3.

Summary of the recommendations for the follow-up of children and adults (both treated and untreated) with XLH

Examination	0–5 years	5 years to start of puberty (9–12 years)	Pubertya	Adults
Frequency of visits	Monthly to thrice monthly	3–6 months	3 months	6–12 months
Height, weight, IMD and ICD	✓	✓	✓	✓
Head circumference and skull shape	✓	NA	NA	NA
Presence of rickets, pain, stiffness and fatigue	✓	✓	✓	✓b
Neurological examination (consequences of craniosynostosis and spinal stenosis)	✓	✓	✓	✓
Musculoskeletal function, 6MWTc	Not feasible	Once a year	Once a year	Once a year
Orthopaedic examination	Once a year in the presence of significant leg bowing			Once a yeard
Dental examination	Twice yearly after tooth eruption	Twice yearly	Twice yearly	Twice yearly
Hearing test	Not feasible	From 8 years: hearing evaluation if symptoms of hearing difficulties
Serum levels of ALP (children), BAP (adults), calcium, phosphate, PTH and creatinine; eGFR	✓	✓	✓	✓
25(OH) vitamin D levels	Once a year	Once a year	Once a year	Once a year
Urine test: calcium:creatinine ratioe	Every 3 to 6 months on conventional treatment and burosumab treatment
Fasting serum phosphate levels and TmP/GFR	• On burosumab treatment: every 2 weeks during the first month, every 4 weeks during the following 2 months and thereafter as appropriate • Titration period: between injections, ideally 7–11 days after last injection to detect hyperphosphataemia • After achievement of a steady state (which can be assumed after 3 months of a stable dose): preferentially directly before injections (children) or during the last week before the next injection (adults) to detect underdosing • Also measured 4 weeks after dose adjustment
1,25(OH)2 vitamin D levels	Every 3 to 6 months in patients on burosumab treatment (analysed together with UCa)
Blood pressure	Twice yearly	Twice yearly	Twice yearly	Twice yearly
Renal ultrasonography	Every 1–2 years on conventional or burosumab treatment
Left wrist and/or lower limbs radiographs	• If leg bowing does not improve upon treatment (children) • If surgery is indicated • Focused on any area of localized persistent bone pain • In case of short stature (bone age assessment)		In adolescents with persistent lower limb deformities when they are transitioning to adult care	NA
Dental orthopantogram	Not feasible	Based on clinical needs	Based on clinical needs	Based on clinical needs
Fundoscopy and brain MRI	If aberrant shape of skull, headaches or neurological symptoms	If recurrent headaches, declining school/cognitive performances or neurological symptoms
Cardiac ultrasonographyf	In presence of persistent elevated blood pressure (>95th percentile)
QOLg	Not feasible	Every 2 years if available	Every 2 years if available	Every 2 years if available

6MWT, 6-minute walk test⁷⁷; ALP, alkaline phosphatase; BAP, bone alkaline phosphatase; eGFR, estimated glomerular filtration rate^195,196; ICD, intercondylar distance (reference values are given here⁷³); IMD, intermalleolar distance; NA, not applicable; PTH, parathyroid hormone; QOL, quality of life; TmP/GFR, maximum rate of renal tubular reabsorption of phosphate per glomerular filtration rate. ^aThese examinations should also be performed at the time of transition to adult care. ^bAlso search for osteomalacia, pseudofractures, osteoarthritis and enthesopathy. ^cIf available. ^dIn symptomatic patients. ^eUpper normal range (mol/mol): 2.2 (<1 years), 1.4 (1–3 years), 1.1 (3–5 years), 0.8 (5–7 years) and 0.7 (>7 years). ^fAccording to international guidelines. ^gUsing age-appropriate and disease-appropriate QOL scales.