Organic Causes of Failure to Thrive: Diagnostic and Treatment Approach
Direct Answer
For failure to thrive with suspected organic etiology, pursue targeted laboratory evaluation only when clinical history or physical examination suggests specific underlying disease, as routine screening identifies organic causes in less than 1.4% of cases. 1
Clinical Recognition of Organic FTT
Organic failure to thrive results from defects in nutrient assimilation, excessive caloric loss, increased energy requirements, or prenatal insults. 2 Key clinical indicators that should prompt investigation for organic causes include:
- Muscle wasting, decreased subcutaneous fat, and abnormalities of hair, skin, and nails suggesting nutritional deficiencies 3
- Oral-motor dysfunction indicating inadequate caloric intake 3
- Recurrent infections particularly sinopulmonary infections with failure to thrive 4
- Vomiting, lethargy, unusual odor, or developmental delay suggesting metabolic disorders 5
- Hepatosplenomegaly, chronic diarrhea, or hypotonia indicating storage disorders or metabolic disease 5
Initial Diagnostic Workup
Essential History Components
Obtain detailed prenatal and birth history including polyhydramnios, prematurity, and birth measurements to identify risk factors. 3 Document:
- Feeding difficulties, swallowing issues, vomiting, or gastroesophageal reflux 3
- Family history of growth disorders, genetic conditions, or metabolic diseases 3
- Growth trajectory using standardized WHO growth charts for weight, height, and head circumference 3
First-Line Laboratory Testing
When organic disease is suspected based on clinical findings, obtain:
- Complete blood count to assess for anemia, infection, or hematologic disorders 3
- Comprehensive metabolic panel including electrolytes, renal function, and acid-base status 3
- Thyroid function tests to evaluate for hypothyroidism 3
- Urinalysis to assess for renal tubular disorders 3
Specialized Metabolic Evaluation
When to Suspect Inborn Errors of Metabolism
Consider metabolic disorders when FTT presents with acute illness, hyperammonemia, hypoglycemia, ketolactic acidosis, neurologic abnormalities, seizures, ataxia, hypotonia, lethargy, coma, developmental delay, unexplained metabolic acidosis, unusual odor, macrocephaly, or liver failure. 5
Metabolic Testing Strategy
Acylcarnitine profile analysis using tandem mass spectrometry should be performed to screen for fatty acid oxidation disorders and organic acidemias when metabolic disease is suspected. 5 This detects:
- Fatty acid oxidation disorders (MCAD, VLCAD, LCHAD, CPT deficiencies) presenting with hypoketotic hypoglycemia, liver disease, cardiomyopathy, and sudden death 5
- Organic acidemias (isovaleric acidemia, methylmalonic acidemia, propionic acidemia, glutaric acidemia type I) presenting with recurrent acute illness, vomiting, lethargy, and developmental delay 5
Comprehensive metabolic evaluation should include plasma amino acids, urine organic acids, and plasma carnitine (free and total) alongside acylcarnitine analysis. 5
Urine Organic Acid Analysis
Urine organic acid analysis identifies disorders of amino acid metabolism, fatty acid oxidation, energy metabolism, purine/pyrimidine metabolism, and neurotransmission. 5 This testing is indicated for:
- Neonatal or late-onset acute illness with hyperammonemia, hypoglycemia, or ketolactic acidosis 5
- Neurologic abnormalities including seizures, ataxia, hypotonia, lethargy, developmental delay 5
- Unexplained metabolic acidosis or unusual odor 5
Specialized Referrals
Gastroenterology Referral
Refer to gastroenterology for persistent feeding difficulties, reflux, or poor growth despite initial interventions. 3 Evaluate for:
- Gastroesophageal reflux and swallowing dysfunction 3
- Malabsorption disorders
- Pancreatic insufficiency
Genetics Referral
Comprehensive genetic evaluation including chromosomal microarray or specific gene panels should be pursued for children with suspected genetic disorders, particularly when multiple congenital anomalies, dysmorphic features, or family history suggests genetic etiology. 3
Additional Specialty Consultations
Consider endocrinology referrals for suspected hormonal disorders, neurology for neurologic abnormalities, and immunology for recurrent infections with failure to thrive. 3, 4
Critical Pitfalls to Avoid
Do not perform extensive laboratory investigations routinely, as organic etiology is identified in less than 1.4% of cases when investigations are not guided by clinical suspicion. 1 Most cases of FTT are non-organic and respond to behavioral and nutritional interventions. 6, 1
When investigations are positive for organic disease, the etiology is almost always suspected based on history and physical examination findings. 1 Therefore, limit evaluations to children with clear symptoms of organic disease or those who fail to grow despite appropriate behavioral and nutritional interventions. 1
Treatment Approach
Early intervention is essential because children may develop significant long-term sequelae from nutritional deficiency. 2 Treatment includes:
- Behavioral and nutritional interventions as first-line therapy for most cases 6
- Treatment of underlying organic disease when identified 6
- Regular follow-up to monitor growth response to interventions 3
Treatment is most effective when applied as early as possible to prevent social and health detrimental outcomes. 6