Comprehensive Blood Workup for Autism Evaluation
A comprehensive blood workup for autism evaluation should include high-resolution chromosomal analysis, Fragile X testing, chromosomal microarray analysis, and targeted metabolic screening when clinically indicated. 1, 2
Tiered Approach to Blood Testing
First-Tier Tests (Essential for All Patients)
- High-resolution chromosomal analysis (peripheral karyotype)
- DNA testing for Fragile X syndrome
- Chromosomal microarray analysis (CMA)
These tests have the highest diagnostic yield, with chromosomal microarray showing a diagnostic yield of approximately 24% in ASD cases 2.
Second-Tier Tests (Based on Clinical Indicators)
- MECP2 gene testing (for females only)
- PTEN gene testing (if head circumference is >2.5 SD above mean - 5% yield in this population) 1, 2
Metabolic Testing (When Clinically Indicated)
- Standard metabolic screening when clinical indicators are present:
- Urine mucopolysaccharides and organic acids
- Serum lactate, amino acids, ammonia, and acyl-carnitine profile 1
Clinical Indicators for Metabolic Testing
Metabolic disorders in autism are considered "low incidence yet high impact" 1. Consider metabolic testing when the following are present:
- True developmental regression (neurodegeneration)
- Worsening neurological symptoms
- Lethargy or poor physical endurance
- Seizures
- Physiologic abnormalities such as acidosis 1
Special Considerations
Mitochondrial Abnormalities
Consider testing for mitochondrial dysfunction when there is:
- Loss of speech after febrile illness or immunization with subsequent encephalopathy
- Constitutional symptoms
- Hypotonia
- Repeated regressions after age 3
- Multiple organ dysfunctions 1
Targeted Metabolic Profiles
Recent research has identified specific metabolic profiles that may be associated with ASD, particularly in children under 5 years. These include elevated levels of:
- Citrulline (amino acid)
- Multiple acyl-carnitines (C2, C4DC/C5OH, C10, C12, C14:2, C16, C16:1, C18:1) 3
Importance of Genetic Testing
Despite clear guidelines recommending genetic testing as standard of care for ASD evaluation, studies show that only about 30% of patients receive at least one indicated genetic test, and only 11% receive the full recommended genetic testing panel 4. This represents a significant gap in clinical practice.
Common Pitfalls to Avoid
Relying solely on metabolic testing without genetic evaluation: Genetic testing has a higher diagnostic yield and should be performed first.
Ordering unnecessary tests: Follow the tiered approach based on clinical presentation rather than ordering a full battery of tests for every patient.
Missing clinical indicators for metabolic testing: Be vigilant for signs of metabolic disorders, as early intervention can significantly impact outcomes.
Failing to coordinate with specialists: The primary care physician and clinical geneticist should partner in ordering, scheduling, and coordinating recommended diagnostic testing 1.
Not completing the full diagnostic process: Genetic testing is just one component of a comprehensive autism evaluation that should also include standardized diagnostic instruments such as ADOS-2 and ADI-R 2.
By following this tiered approach to blood testing in autism evaluation, clinicians can maximize diagnostic yield while minimizing unnecessary testing, ultimately improving patient outcomes through earlier diagnosis and more targeted interventions.