Why order amino acid (amino acid) profiles in patients suspected of having conditions related to malnutrition, malabsorption, or inborn errors of metabolism, particularly in pediatric patients or those with a history of gastrointestinal disorders?

Why Order Amino Acid Profiles

Amino acid profiles should be ordered when you suspect inborn errors of metabolism (IEMs), particularly in neonates and infants presenting with unexplained metabolic encephalopathy, hyperammonemia, metabolic acidosis, or failure to thrive, as these tests are essential diagnostic tools that can identify life-threatening but treatable conditions. 1, 2

Primary Clinical Indications

Acute Metabolic Crisis in Neonates and Infants

• Order amino acid profiles immediately in any neonate or infant presenting with lethargy, poor feeding, apnea or tachypnea, and recurrent vomiting, as these symptoms characterize acute metabolic encephalopathy from urea cycle defects, organic acidemias, and amino acid metabolism disorders 2

• Amino acid profiling is critical when hyperammonemia is detected, as it helps differentiate primary urea cycle disorders (which show specific amino acid accumulation patterns) from secondary causes 3, 1

• In pediatric patients with unexplained metabolic acidosis, amino acid analysis combined with organic acid profiling can identify the specific enzymatic defect, as these two tests are complementary and essential for diagnosing most IEMs 1, 4

Severe Malnutrition and Protein Deficit

• Plasma amino acid profiles help characterize protein deficit in children with severe malnutrition, providing objective data about specific amino acid deficiencies that cannot be assessed through routine laboratory tests alone 5

• In children with long-term malnutrition or those receiving parenteral nutrition, amino acid profiling should be considered alongside trace element and vitamin assessment to comprehensively evaluate nutritional status 5

Diagnostic Algorithm for Ordering

When Metabolic Acidosis is Present

• If metabolic acidosis is detected (bicarbonate <22 mmol/L, pH <7.35), order both amino acid analysis and organic acid profiling together, as the pattern of abnormalities across both tests provides the diagnostic signature for specific IEMs 3, 1

• The lactate-pyruvate ratio should be measured concurrently with amino acid profiling, as an elevated L/P ratio combined with altered aminogram patterns and hyperammonemia strongly suggests IEM 4

When Hyperammonemia is Present

• In neonates with hyperammonemia (ammonia >150 μmol/L), amino acid analysis is mandatory to distinguish between different urea cycle enzyme deficiencies, as each shows characteristic amino acid accumulation patterns 3, 2

• Measure plasma amino acids urgently before initiating dialysis or exchange transfusion, as these interventions will alter the diagnostic pattern 6

Unexplained Neurological Symptoms

• Order amino acid profiles in infants with unexplained seizures, developmental delay, or altered mental status, even without metabolic acidosis or hyperammonemia, as conditions like nonketotic hyperglycinemia present with normal acid-base status 2

Interpretation Framework

Pattern Recognition is Critical

• Clinically meaningful interpretation requires evaluating the overall pattern of amino acid abnormalities rather than isolated elevations, as single amino acid elevations can occur from dietary intake, sample handling, or non-metabolic causes 3

• Interpretation should be performed by board-certified laboratory directors with expertise in biochemical genetics, as amino acid profiling is among the most complex metabolic tests 3

Timing and Sample Considerations

• Collect samples during acute metabolic decompensation when possible, as diagnostic sensitivity varies considerably between acute and asymptomatic states—some IEMs show normal amino acid profiles when the patient is clinically stable 3

• The excretion of diagnostic metabolites reflects residual enzyme activity, dietary precursor load, and the patient's anabolic/catabolic status, so clinical context is essential for interpretation 3

Integration with Other Metabolic Testing

Complementary Tests

• Amino acid analysis should be ordered alongside organic acid analysis (urine), as together they identify the majority of treatable IEMs affecting amino acid and organic acid metabolism 1, 4

• In children suspected of malnutrition, amino acid profiling complements routine tests (electrolytes, minerals, triglycerides, serum urea, hemoglobin, pre-albumin) by providing specific information about protein metabolism 5

When to Add Amino Acid Testing to Standard Workup

• Add amino acid profiling to the standard sepsis workup in full-term neonates with no specific risk factors who present with lethargy, poor feeding, and metabolic derangements, as IEMs can mimic sepsis but require entirely different management 2

• In children with chronic gastrointestinal disorders and suspected malabsorption, amino acid profiles can identify specific deficiencies that guide targeted supplementation 5

Common Clinical Pitfalls to Avoid

• Do not delay amino acid testing while waiting for genetic testing results—biochemical diagnosis guides immediate life-saving treatment, while genetic confirmation takes weeks 1, 2

• Avoid ordering amino acid profiles in isolation without clinical context or complementary metabolic tests (organic acids, ammonia, lactate), as interpretation requires the complete metabolic picture 1, 4

• Do not dismiss the possibility of IEM based on negative newborn screening, as many amino acid disorders are not included in standard screening panels and present after the neonatal period 2

• Recognize that dietary protein intake, medications, and sample contamination can cause abnormal amino acid profiles, requiring clinical correlation before concluding a diagnosis 3