Why would a 6‑year‑old have elevated alkaline phosphatase (ALP) and aspartate aminotransferase (AST)?

Elevated Alkaline Phosphatase and AST in a 6-Year-Old

In a 6-year-old child, elevated alkaline phosphatase (ALP) is most commonly physiologic due to active bone growth, while concurrent AST elevation suggests either a transient benign condition (such as benign transient hyperphosphatasemia following a recent viral illness) or, less commonly, an underlying hepatobiliary or bone disorder that requires systematic exclusion.

Understanding Physiologic ALP Elevation in Children

• ALP levels are physiologically 2–3 times adult values in children due to active bone growth, making isolated ALP elevation extremely common and usually benign in this age group. 1
• The upper limit of normal for ALP in children is substantially higher than in adults, and this must be considered when interpreting laboratory results. 1
• Bone-derived ALP accounts for the majority of total ALP in healthy growing children, reflecting osteoblastic activity at growth plates. 1

Benign Transient Hyperphosphatasemia (Most Likely Diagnosis)

Benign transient hyperphosphatasemia (BTH) is the most common cause of markedly elevated ALP in otherwise healthy children aged 6 months to 5 years, characterized by ALP levels often exceeding 1000 U/L (sometimes reaching 2000–14,000 U/L) without clinical or laboratory evidence of bone or liver disease. 2, 3

Key Clinical Features of BTH:

• Peak incidence occurs between 10–24 months of age (median 14 months), though cases are reported up to age 14 years, making a 6-year-old within the possible range. 2
• Often preceded by recent viral illness, gastroenteritis, diarrhea, acute otitis media, or fever within the preceding 2–4 weeks. 2, 3
• The child appears clinically well with no signs of bone disease (no bone pain, fractures, or deformities) or liver disease (no jaundice, hepatomegaly, or abdominal pain). 2, 3
• ALP spontaneously normalizes within 2–4 months without intervention. 4, 2, 3
• Bone turnover markers (osteocalcin, CrossLaps) and parathyroid hormone remain normal, confirming that the ALP elevation does not reflect increased bone remodeling. 4

Why AST May Also Be Elevated:

• Mild AST elevation can accompany BTH, particularly if there was a recent viral infection, as AST is present in multiple tissues (liver, cardiac muscle, skeletal muscle, red blood cells). 5
• AST is significantly less liver-specific than ALT and can be transiently elevated from non-hepatic sources during acute illness. 5

Diagnostic Approach: Excluding Serious Pathology

Step 1: Confirm Hepatobiliary vs. Bone Origin of ALP

• Measure gamma-glutamyl transferase (GGT) concurrently: Elevated GGT confirms hepatobiliary origin; normal GGT strongly suggests bone origin. 1, 6
• If GGT is unavailable or equivocal, obtain ALP isoenzyme fractionation to quantify the percentage from liver versus bone. 1, 6

Step 2: Assess for Hepatobiliary Disease (If GGT Elevated)

• Obtain a complete liver panel: ALT, AST, alkaline phosphatase, total and direct bilirubin, albumin, and prothrombin time/INR. 5, 6
• Fractionate total bilirubin to determine the proportion of direct (conjugated) bilirubin; elevation suggests cholestasis. 1, 6
• Perform abdominal ultrasound as first-line imaging (sensitivity 84.8%, specificity 93.6% for hepatic pathology) to assess for biliary obstruction, hepatomegaly, infiltrative lesions, or structural abnormalities. 1, 5, 6
• If ultrasound is negative but ALP remains elevated, proceed to MRI with MRCP, which is superior for detecting intrahepatic biliary abnormalities and infiltrative disease. 1, 6

Step 3: Assess for Bone Disease (If GGT Normal)

• Check serum calcium, phosphate, parathyroid hormone (PTH), and 25-hydroxyvitamin D to screen for metabolic bone disease, rickets, or hyperparathyroidism. 1, 4
• Bone-specific ALP (B-ALP) can be measured if available, though it is less useful when total ALP is already known to be of bone origin. 1
• Inquire about bone pain, fractures, or skeletal deformities; their absence makes significant bone pathology unlikely. 1, 2

Step 4: Review Recent Illness History

• Document any recent viral infections, gastroenteritis, fever, or respiratory illness within the past 2–4 weeks, as these strongly support BTH. 2, 3
• BTH often follows a benign infectious trigger and requires no specific treatment. 2, 3

When to Adopt a "Wait and See" Approach

If the child is clinically well, has normal GGT (or predominantly bone-derived ALP on fractionation), normal calcium/phosphate/PTH/vitamin D, and a history of recent viral illness, the diagnosis is almost certainly benign transient hyperphosphatasemia. 2, 3

Recommended Monitoring:

• Repeat ALP measurement in 4–8 weeks to confirm downward trend. 2, 3
• Expect normalization within 2–4 months; persistent elevation beyond 4 months warrants further investigation. 4, 2, 3
• Avoid unnecessary imaging, bone scans, or vitamin D supplementation in the absence of clinical or biochemical evidence of bone or liver disease. 4, 2, 3

Red Flags Requiring Urgent Evaluation

• ALP >10× upper limit of normal (severe elevation) requires expedited workup for serious pathology such as biliary obstruction, infiltrative disease, or malignancy. 1, 6
• Elevated direct bilirubin (>2 mg/dL) suggests cholestatic liver disease and mandates immediate hepatobiliary evaluation. 1, 6
• Clinical signs of liver disease: jaundice, hepatomegaly, splenomegaly, ascites, or coagulopathy. 5, 6
• Clinical signs of bone disease: bone pain, pathologic fractures, skeletal deformities, or failure to thrive. 1, 2
• Persistent ALP elevation beyond 4 months without normalization. 4, 2, 3

Important Caveats

• Do not assume all ALP elevations in children are benign; systematic exclusion of hepatobiliary and bone disease is mandatory before diagnosing BTH. 2, 3
• In infants with parenteral nutrition-associated liver disease (PNALD), elevated ALP predominantly reflects bone disease (metabolic bone disease) rather than liver disease, even when direct bilirubin is elevated. 7
• Wilson disease presenting as acute liver failure can show a paradoxical pattern with modest transaminase elevations, markedly low ALP, and an ALP/total bilirubin ratio <2, though this is exceedingly rare in a 6-year-old. 8
• Primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease; if the child has chronic diarrhea or abdominal pain, consider PSC and obtain MRCP. 1, 6

Practical Algorithm for a 6-Year-Old with Elevated ALP and AST

1. Day 0: Obtain GGT, complete liver panel (ALT, AST, ALP, total/direct bilirubin, albumin, INR), calcium, phosphate, PTH, 25-hydroxyvitamin D. 1, 5, 6
2. If GGT is normal: Diagnosis is likely BTH; repeat ALP in 4–8 weeks and expect normalization within 2–4 months. 2, 3
3. If GGT is elevated: Perform abdominal ultrasound within 1 week to assess for biliary obstruction or infiltrative disease. 1, 6
4. If ultrasound is abnormal: Refer urgently to pediatric gastroenterology/hepatology. 5, 6
5. If ultrasound is normal but ALP remains elevated: Proceed to MRI with MRCP within 2–4 weeks. 1, 6
6. If all tests are normal and ALP normalizes within 4 months: Diagnosis confirmed as BTH; no further workup needed. 2, 3

The key is recognizing that isolated ALP elevation in a healthy 6-year-old following a recent viral illness is almost always benign transient hyperphosphatasemia, but systematic exclusion of serious pathology is essential before adopting a watchful waiting approach. 2, 3