Elevated Alkaline Phosphatase in Children
Initial Approach
In children with isolated elevated alkaline phosphatase, first determine if this represents normal physiological bone growth (especially during puberty) or benign transient hyperphosphatasemia (BTH), which requires only observation and repeat testing in 3-4 months, rather than extensive workup. 1, 2, 3
Diagnostic Algorithm
Step 1: Clinical Context Assessment
- Check for symptoms or signs of disease: Look specifically for bone pain, skeletal deformities (leg bowing, rachitic rosary), growth impairment, dental abnormalities, jaundice, hepatomegaly, or recent illness 1, 3
- Age matters: BTH occurs predominantly in children under 24 months (median 14 months), with 87% of cases in this age group 3
- Recent illness history: Many BTH cases follow fever, gastroenteritis, diarrhea, acute otitis media, or viral infections 3
Step 2: Initial Laboratory Workup
If the child is asymptomatic with isolated ALP elevation, obtain:
- Comprehensive metabolic panel: Serum calcium, phosphate, creatinine, liver transaminases (ALT/AST), bilirubin 1
- PTH and 25(OH) vitamin D levels to exclude metabolic bone disorders 1, 4
- Calculate TmP/GFR (tubular maximum reabsorption of phosphate per glomerular filtration rate) to assess for renal phosphate wasting 1
Step 3: Pattern Recognition
Benign Transient Hyperphosphatasemia (BTH):
- ALP often markedly elevated (>1000 U/L, range 1002-14,589 U/L) 3
- Normal calcium, phosphate, liver enzymes, and PTH 2, 3
- No clinical signs of bone or liver disease 2, 3
- Management: "Wait and see" approach—repeat ALP in 3-4 months to confirm spontaneous resolution 2, 3
- Avoid unnecessary imaging, biopsies, or subspecialty referrals 2, 3
Pathological Causes Requiring Treatment:
X-linked Hypophosphataemia (XLH):
- Low phosphate + elevated ALP + low TmP/GFR (opposite pattern from hypophosphatasia) 5, 4
- May have bone deformities, short stature, dental abscesses 5
- Treatment: Oral phosphate supplements (20-60 mg/kg/day elemental phosphorus divided 4-6 times daily) plus active vitamin D (calcitriol or alfacalcidol) 5
- Goal is normalization of ALP and radiological healing of rickets 5
Hepatobiliary Disease:
- Elevated transaminases, bilirubin, or GGT alongside ALP 5
- In autoimmune hepatitis/primary sclerosing cholangitis overlap, ALP remains elevated despite immunosuppression 5
- Consider MRCP if ALP doesn't normalize with treatment 5
Hypophosphatasia (HPP):
- Low ALP (not elevated—opposite problem) with premature tooth loss, bone pain 4
- This is the differential when ALP is inappropriately low, not high 4
Step 4: When to Pursue Further Workup
Proceed with additional testing if:
- Abnormal calcium, phosphate, or liver enzymes on initial labs 1
- Clinical signs of bone disease: Deformities, growth failure, bone pain 1
- ALP remains elevated beyond 4 months (excludes BTH) 2, 3
- Elevated ALP with low phosphate and low TmP/GFR (suggests XLH) 5, 1
Additional studies may include:
- ALP isoenzyme fractionation (bone vs. liver origin) 6, 7
- Skeletal radiographs if bone disease suspected 1
- Abdominal ultrasound if hepatobiliary disease suspected 2
Common Pitfalls to Avoid
- Don't reflexively order extensive imaging or subspecialty referrals for isolated ALP elevation in healthy young children—BTH is common and self-limited 2, 3
- Don't normalize phosphate levels as a treatment goal in XLH—fasting phosphate won't normalize with oral supplements 5
- Don't give phosphate supplements without active vitamin D—this causes secondary hyperparathyroidism and worsens renal phosphate wasting 5
- Don't administer phosphate with calcium-rich foods or supplements—they precipitate in the gut and reduce absorption 5
- Don't miss the seasonal pattern—BTH peaks in autumn/early winter, though this may reflect detection bias 3
Monitoring for Confirmed Pathological Causes
For children diagnosed with XLH or other metabolic bone diseases: