Recommended Bloodwork for Autism Spectrum Disorder (ASD)
While routine metabolic screening is not universally recommended for all individuals with ASD, targeted bloodwork should be performed when specific clinical indicators are present, as metabolic disorders in ASD are considered "low incidence yet high impact." 1, 2
First-Tier Bloodwork Evaluation
When clinical indicators are present, the following tests should be ordered:
Basic Screening:
- Complete blood count (CBC)
- Serum metabolic profile
- Serum amino acids
- Urine screening for glycosaminoglycans 1
Genetic Testing:
- Chromosomal microarray analysis (diagnostic yield: 24%)
- Fragile X testing (particularly in males, diagnostic yield: 2-3%)
- MECP2 gene testing (females only)
- PTEN gene testing (if head circumference >2.5 SD above mean, diagnostic yield: 5%) 1, 2
Clinical Indicators That Warrant Metabolic Testing
Metabolic testing should be considered when any of these signs/symptoms are present:
- True developmental regression (neurodegeneration)
- Worsening neurological symptoms
- Lethargy or poor physical endurance
- Seizures
- Acid/base or electrolyte disturbances
- Cyclic vomiting
- Dermatologic changes (alopecia, hypertrichosis, pigmented skin eruptions)
- Gastrointestinal dysfunction or gastroparesis
- Hypotonia/dystonia
- Lactic acidosis
- Multisystem involvement (cardiac, hepatic, or renal)
- Poor growth or microcephaly 1, 2
Specific Metabolic Tests to Consider
When metabolic disorders are suspected, the following tests should be ordered:
- Urine organic acids
- Serum lactate
- Serum ammonia
- Acyl-carnitine profile 2
Recent research has identified a subset of ASD patients with distinctive metabolic profiles, particularly showing abnormalities in acyl-carnitines (C2, C4DC/C5OH, C10, C12, C14:2, C16, C16:1, C18:1) and the amino acid citrulline 3. This profile may be particularly relevant in children under 5 years of age.
Mitochondrial Dysfunction Assessment
Consider mitochondrial testing when these specific indicators are present:
- Loss of speech after febrile illness or immunization with subsequent encephalopathy
- Constitutional symptoms
- Hypotonia
- Repeated regressions after age 3
- Multiple organ dysfunctions 1
Important Caveats and Pitfalls
Avoid unnecessary testing: Ordering large numbers of tests without specific clinical indications is not recommended as it is invasive, wasteful, and unlikely to generate useful data 4.
Remember high-impact conditions: While metabolic disorders in ASD are relatively rare, they can have significant impacts on morbidity and mortality if undetected. For example, 5% of patients with untreated phenylketonuria meet diagnostic criteria for autism 1.
Consider timing: Some metabolic disorders like Sanfilippo syndrome may not show obvious clinical indicators for decades after the initial ASD diagnosis 1.
Recognize comorbidities: Individuals with ASD have higher rates of depression (20% vs 7%), anxiety (11% vs 5%), sleep difficulties (13% vs 5%), and epilepsy (21% with co-occurring intellectual disability vs 0.8%) compared to the general population 5. These may influence test interpretation.
Audiogram requirement: A complete audiogram is mandatory to rule out hearing loss that may mimic ASD symptoms 2.
By following this structured approach to bloodwork evaluation in ASD, clinicians can identify potentially treatable metabolic conditions while avoiding unnecessary testing, ultimately improving patient outcomes through targeted interventions.