Laboratory Testing for Autistic Individuals on Multiple Psychotropic Medications and Nutritional Supplements
Essential Baseline Laboratory Panel
Order the following tests immediately for both the 80-year-old and 19-year-old patients to assess nutritional status and medication-related metabolic effects:
Core Nutritional Assessment
Vitamin B12 with methylmalonic acid and homocysteine: These functional markers are more sensitive than serum B12 alone for detecting true B12 deficiency, particularly important in patients on multiple psychotropic medications 1, 2.
25-hydroxyvitamin D: Vitamin D deficiency is extremely common in individuals with autism and should be routinely screened 2.
Complete blood count (CBC): Essential to detect anemia with elevated mean corpuscular volume, which may indicate B12 or folate deficiency and is a red flag for metabolic disorders 3, 4.
Iron studies (ferritin and total iron binding capacity): Iron metabolism abnormalities are common in autism and may interact with folate pathway function 1, 2.
Comprehensive metabolic panel: Includes electrolytes, liver function tests, kidney function, and glucose to monitor for medication-induced metabolic complications and detect acid/base disturbances that suggest metabolic disorders 3, 4.
Folate Pathway and Metabolic Screening
Folate receptor autoantibodies (FRAA): This is the primary biomarker recommended by the American Academy of Pediatrics to identify patients who may benefit from leucovorin therapy, especially if any developmental regression has occurred 1, 2.
Serum amino acids: Part of metabolic screening when patients show signs of metabolic disorders, particularly relevant given the profound intellectual disability 3, 4.
Free and total carnitine with acyl-carnitine profile: Carnitine deficiency is defined by acyl-free carnitine ratio >0.4 or total serum carnitine <40 µmol/L and is treatable with L-carnitine 50 mg/kg/day divided twice daily 2.
Antipsychotic Medication Monitoring
Fasting lipid panel: Hypercholesterolemia occurs far more frequently than expected with antipsychotic use (observed-to-expected ratio >6 times), particularly with valproic acid (>120 times expected) 5.
Fasting glucose and hemoglobin A1c: Monitor for metabolic syndrome and diabetes risk from antipsychotic medications 5.
Prolactin level: Gynecomastia and hyperprolactinemia occur more than 6 times expected frequency with risperidone 5.
Creatine kinase (CK): Rhabdomyolysis with valproic acid occurs >120 times more frequently than expected; monitor baseline and periodically 5.
Conditional Testing Based on Clinical Red Flags
When to Pursue Expanded Metabolic or Mitochondrial Testing
The American College of Medical Genetics states that routine metabolic testing should NOT be performed for every autistic patient—it is indicated only when specific red-flag signs are present 3, 4:
Developmental regression outside the typical 18-24 month speech loss window or regression after age 3 warrants lactate, pyruvate, and mitochondrial function studies 3, 1, 4.
Seizures, especially refractory types, require consideration of cerebral folate deficiency testing and genetic testing for MTHFR and folate metabolism pathway variants 3, 1, 4.
Hypotonia, dystonia, or movement disorders (extrapyramidal signs, ataxia, parkinsonism) mandate aggressive folate pathway and mitochondrial testing 3, 1, 4.
Cyclic vomiting, lethargy, poor physical endurance, or worsening neurological symptoms suggest mitochondrial disease and require lactate, pyruvate, and appropriate mitochondrial studies 3, 4.
Multisystem involvement (cardiac, hepatic, or renal dysfunction detected on metabolic panel) necessitates expanded metabolic and mitochondrial evaluation 3, 4.
Lactic acidosis or other acid/base disturbances on metabolic panel require immediate mitochondrial workup 3, 4.
Poor growth or microcephaly (or macrocephaly >98th percentile, which would prompt PTEN testing) warrant metabolic screening 3, 1.
Monitoring Schedule During Treatment
Recheck all baseline labs after 3 months of any new nutritional supplement or medication adjustment 1.
Monitor weight and BMI at every visit given the high risk of antipsychotic-induced weight gain and metabolic syndrome 5.
Assess for extrapyramidal symptoms clinically at each visit, as extrapyramidalism occurs >6 times expected frequency with antipsychotics 5.
Repeat lipid panel, glucose, and A1c every 3-6 months while on antipsychotic medications 5.
Critical Pitfalls to Avoid
Do not overlook micronutrient deficiencies despite adequate caloric intake—patients on restricted diets or with feeding difficulties are at high risk 2, 6.
Do not delay metabolic screening when red flags are present—cerebral folate deficiency and mitochondrial disorders are "low incidence yet high impact" and are treatable if identified early 3, 1, 4.
Do not miss medication-induced metabolic complications—half of adverse events in autistic adults on antipsychotics involve nervous or metabolic systems, and many occur far more frequently than drug labels suggest 5.
Do not order chromosomal microarray or extensive genetic panels unless clinically indicated—the diagnostic yield is only 40% and should not replace targeted metabolic testing when specific symptoms are present 2.
Do not assume normal serum B12 rules out deficiency—always order methylmalonic acid and homocysteine for functional assessment 1, 2.