What is the management approach for a 19-year-old male presenting with rickets?

Management of Rickets in a 19-Year-Old Male: Case Presentation Framework

History

For a 19-year-old male presenting with rickets, obtain a detailed history focusing on:

• Onset and duration of skeletal symptoms (leg bowing, bone pain, short stature) – symptoms developing after age 2 years suggest autosomal dominant hypophosphataemic rickets or tumor-induced osteomalacia rather than X-linked hypophosphataemia (XLH) 1
• Family history of rickets, short stature, or bone deformities – positive family history supports XLH diagnosis; male-to-male transmission excludes XLH 1
• Dietary history including calcium intake, vitamin D supplementation, and dairy product consumption – inadequate intake suggests nutritional rickets 2, 3
• Sun exposure history – limited sunlight exposure, especially in dark-skinned individuals or those living in apartments, increases risk of vitamin D deficiency 2, 3
• Dental history – recurrent dental abscesses and oral infections suggest impaired tooth mineralization seen in XLH 1
• Medication history – certain drugs can cause iatrogenic proximal tubulopathy 1
• Symptoms of renal disease – acidosis, glucosuria, aminoaciduria suggest Fanconi syndrome 1

General Physical Examination

Key findings to document:

• Height and growth velocity – disproportionate short stature is characteristic of XLH 1
• Weight and nutritional status – assess for malnutrition contributing to nutritional rickets 3
• Skin pigmentation – dark-skinned individuals have higher risk of vitamin D deficiency 3, 4
• Head shape and circumference – abnormal skull shape may indicate craniosynostosis (seen in XLH up to age 5 years, but relevant if symptoms began earlier) 1

Musculoskeletal/Bone Examination

Critical skeletal findings:

• Lower limb deformities – measure intercondylar distance (genu varum/bow legs) or intermalleolar distance (genu valgum/knock knees); windswept deformity (valgus in one knee, varus in the other) is characteristic of XLH 1
• Joint widening – particularly at wrists, knees, and ankles due to metaphyseal expansion 5
• Bone pain and tenderness – assess severity and distribution 1
• Limb length discrepancy – document any asymmetry 1
• Spinal examination – check for lordosis, kyphosis, or scoliosis 1
• Gait assessment – perform 6-minute walk test to quantify functional impairment 1
• Torsional profile of lower limbs – assess rotation deformities 1

Systemic Examination

Cardiovascular:

• Blood pressure measurement – elevated BP and left ventricular hypertrophy reported in some XLH patients 1

Dental:

• Oral examination – look for dental abscesses, poor dentition, and signs of impaired mineralization 1
• Consider dental orthopantomogram if oral manifestations present 1

Neurological:

• Assess for headache, vomiting – may indicate craniosynostosis, Chiari 1 malformation, or syringomyelia in XLH 1
• Hearing evaluation – auditory complications can occur in XLH 1

Renal:

• Signs of chronic kidney disease – relevant for secondary causes of rickets 1

Laboratory Investigations

Essential biochemical workup:

• Serum phosphate – low in phosphopenic rickets (XLH and hereditary forms); normal or low in nutritional rickets 6, 5
• Serum calcium – normal or low-normal in phosphopenic rickets; low in nutritional rickets 6, 5
• Alkaline phosphatase (ALP) – elevated in all active rickets types; reliable biomarker of disease activity 1, 6
• 25-hydroxyvitamin D [25(OH)D] – low in nutritional rickets; normal in phosphopenic rickets 6, 5
• 1,25-dihydroxyvitamin D – low or inappropriately normal in phosphopenic rickets; may be elevated in nutritional rickets after phosphate correction 6
• Parathyroid hormone (PTH) – normal or slightly elevated in phosphopenic rickets; elevated in nutritional rickets 6
• Urinary calcium – low in active rickets; increases as rickets heals 6
• Urinary phosphate and TmP/GFR calculation – confirms renal phosphate wasting in phosphopenic rickets 6
• FGF23 levels – elevated in XLH but should not be used for routine diagnosis or monitoring due to assay variability 6

Additional tests based on differential diagnosis:

• Renal function tests – creatinine, BUN to assess for renal disease 1
• Urinalysis – check for glucosuria, aminoaciduria, proteinuria suggesting Fanconi syndrome 1
• Genetic testing – PHEX gene analysis if XLH suspected; extended molecular genetic analysis for unclear cases 1

Imaging Studies

Radiographic evaluation:

• Wrist and knee X-rays – show fraying and irregularity of growth plates, metaphyseal widening, cupping, and loss of sharp metaphyseal margins 1, 5
• Lower extremity long films – document severity of leg bowing, assess limb alignment in coronal and sagittal planes 1
• Bone age assessment – X-ray of left wrist to determine growth potential 1
• Renal ultrasound – screen for nephrocalcinosis, especially if considering phosphate therapy 1
• Brain/spinal MRI – if symptomatic (headache, vomiting, abnormal skull shape) to exclude craniosynostosis, Chiari 1 malformation, or syringomyelia; use black bone sequence to avoid radiation 1

Note: DXA or peripheral quantitative CT have limited value in diagnosing osteomalacia in rickets 1

Diagnostic Algorithm

Step 1: Distinguish phosphopenic from calcipenic rickets

• Low phosphate + normal 25(OH)D + normal/low-normal calcium = phosphopenic rickets 6
• Low 25(OH)D + low calcium + elevated PTH = nutritional (calcipenic) rickets 6, 5

Step 2: If phosphopenic rickets, determine etiology

• Positive family history + elevated FGF23 + PHEX mutation = XLH 1
• Hypercalciuria before treatment = hereditary hypophosphataemic rickets with hypercalciuria (HHRH) 1
• Acidosis, glucosuria, aminoaciduria = Fanconi syndrome 1
• Symptoms after age 2 years = consider autosomal dominant hypophosphataemic rickets or tumor-induced osteomalacia 1

Management Approach

For Nutritional Rickets:

Treatment regimen:

• Vitamin D supplementation is the primary treatment – single dose of 300,000 units IM or oral equivalent 7
• Calcium supplementation (3g calcium lactate daily) enhances response, particularly when combined with vitamin D 7
• Best response achieved with combination therapy of vitamin D plus calcium compared to either alone 7
• Monitor weekly with serum calcium, phosphorus, and ALP until normalization 7
• Repeat X-rays at 2 and 4 weeks to assess healing 7

For X-Linked Hypophosphataemia (XLH):

Conventional therapy (if burosumab unavailable):

• Oral phosphate supplementation at 20-60 mg/kg/day (0.7-2.0 mmol/kg/day) based on phenotype severity 1
• Active vitamin D (calcitriol or alfacalcidol) must always accompany phosphate to prevent secondary hyperparathyroidism 1
• Adjust doses to maintain PTH, serum calcium, and urinary calcium within normal range 1
• Goal: Normalize ALP levels and achieve radiological healing of rickets 1

Burosumab therapy (preferred if available):

• Starting dose 0.5-1.0 mg/kg subcutaneously every 4 weeks to achieve serum phosphate >2.5 mg/dL 1
• Superior to conventional therapy for preventing progressive hyperparathyroidism 1
• Monitor serum phosphate and adjust dose accordingly; reduce by 50% if phosphate exceeds 5.0 mg/dL 1

Multidisciplinary management:

• Orthopedic consultation for substantial limb deformities requiring surgical correction 1
• Dental care with twice-yearly examinations after tooth eruption 1
• Physical therapy and rehabilitation for functional impairment 1
• Pain management consultation if persistent symptoms 1
• Regular follow-up with metabolic bone disease specialist 1

Critical Pitfalls to Avoid:

• Never give phosphate alone in XLH – always combine with active vitamin D to prevent hyperparathyroidism 1
• Do not rely on FGF23 levels for routine diagnosis or monitoring due to assay variability 6
• Serum phosphate may be normal in first 3-4 months of life even in XLH, potentially delaying diagnosis 6
• Radiographic features can be misinterpreted as fractures – ensure experienced radiologist review 3
• Vitamin D insufficiency is common but frank rickets is rare – distinguish between deficiency and disease 6
• Monitor for nephrocalcinosis with renal ultrasound when using phosphate therapy 1