What initial laboratory tests should be ordered for a 17-year-old female with high-functioning autism (Autism Spectrum Disorder) and obesity, in addition to a complete blood count (CBC), comprehensive metabolic panel (CMP), thyroid panel, insulin, cortisol, hemoglobin A1c (HbA1c), and lipid profile?

Additional Laboratory Testing for a 17-Year-Old Female with Autism and Obesity

Add vitamin D, folate receptor autoantibodies (FRAA), and consider screening for polycystic ovarian syndrome (PCOS) with testosterone and DHEA-S levels given the combination of autism, obesity, and female sex.

Essential Additional Tests

Metabolic and Nutritional Screening

• Vitamin D (25-OH vitamin D): Patients with obesity frequently have micronutrient deficiencies despite consuming calorically dense foods, and vitamin D deficiency is particularly common 1
• Folate receptor autoantibodies (FRAA): This is the primary biomarker recommended by the American Academy of Pediatrics to identify ASD patients who may benefit from leucovorin therapy, particularly relevant if there are any signs of developmental regression or metabolic concerns 2
• Serum amino acids: Metabolic screening including serum amino acid analysis should be considered in ASD patients showing signs of metabolic disorders, and research shows specific amino acid alterations (particularly citrulline) in subsets of ASD patients 3, 4, 5

Hormone and PCOS Screening

• Total and free testosterone: Obesity in adolescent females increases risk for PCOS, and the physical exam should assess for hirsutism associated with this condition 1
• DHEA-S (dehydroepiandrosterone sulfate): Part of comprehensive PCOS evaluation in obese adolescent females 1
• Consider LH/FSH ratio: If PCOS is suspected based on clinical presentation 1

Additional Metabolic Markers

• Homocysteine and methylmalonic acid: These markers are more sensitive than serum B12 alone for assessing functional B12 status and folate metabolism, which is relevant in ASD patients 2
• Ferritin and total iron binding capacity: Iron metabolism issues should be investigated in ASD patients, particularly when considering folate pathway abnormalities 2

Conditional Testing Based on Clinical Presentation

If Mitochondrial Dysfunction Suspected

Look for these clinical indicators: constitutional symptoms, hypotonia, repeated regressions after age 3, multiple organ dysfunctions, worsening neurological symptoms, lethargy, poor physical endurance, or seizures 3

If present, consider:

• Lactate and pyruvate: Key indicators of mitochondrial dysfunction 3, 4
• Acyl-carnitine profile: Research shows specific acyl-carnitines (C2, C4DC/C5OH, C10, C12, C14:2, C16, C16:1, C18:1) are significantly elevated in subsets of ASD patients and may identify metabolic phenotypes 4, 5

If Cerebral Folate Deficiency Suspected

Consider if there is developmental regression outside typical speech loss at 18-24 months, seizures, hypotonia/dystonia, or movement disorders 2

If present, add:

• Genetic testing for MTHFR and folate metabolism pathway variants: This guides leucovorin therapy decisions 2

Important Clinical Considerations

Obesity-Related Complications in ASD

• Children with ASD have 1.85 times greater odds of obesity compared to controls and significantly increased risk of obesity-related metabolic complications 6
• Screen for obstructive sleep apnea: Use Epworth Sleepiness Scale or STOPBANG questionnaire, as this is common in severe obesity 1
• Assess for acanthosis nigricans on physical exam: This indicates insulin resistance and is particularly relevant given research showing ASD patients may have altered insulin resistance patterns 1, 7

Medication Review

• Review all current medications for weight-gaining effects: mood stabilizers, antipsychotics, antiepileptic drugs, and selective serotonin reuptake inhibitors are significantly associated with obesity in ASD patients 6
• Consider switching to weight-neutral alternatives when clinically appropriate 1

Genetic Testing Considerations

• Chromosomal microarray (CMA): The American Academy of Pediatrics recommends CMA as first-tier genetic testing for unexplained ASD, though this is more relevant for diagnostic evaluation than obesity management 1
• This may have already been completed during initial ASD diagnosis, but if not performed and etiology is unexplained, consider referral to clinical genetics 1

Common Pitfalls to Avoid

• Don't assume normal lipids: Despite psychotropic medication use, ASD patients may have lower cholesterol and glucose levels than expected, so interpret results in context 8
• Don't overlook micronutrient deficiencies: Obese patients are frequently malnourished with multiple micronutrient deficiencies despite excess caloric intake 1
• Don't miss PCOS: The combination of obesity, female sex, and adolescence creates high risk for PCOS, which requires specific hormonal evaluation 1
• Don't delay metabolic screening if clinical indicators present: While routine metabolic testing isn't recommended for all ASD cases, when metabolic abnormalities are suspected, folate pathway and mitochondrial testing should be pursued aggressively 3, 2