23-Month-Old Female with Regressive Autism
Case Clinician: Stephanie Cave, MD
Case Author: Cass Nelson-Dooley
“After four months of treatment with an allergen-free diet, nutrients, digestive enzymes, probiotics, chelation, hyperbaric oxygen, and ABA, TY’s mood improved. Her speech returned and she regained social contact. Years later it was unbelievable to her neurologist that she had ever had the diagnosis of autism.”
A normally developing child developed regressive autism at 18 months. The child lost the ability to speak, make eye contact, and to interact socially. She developed repetitive movements and self-injurious behavior and after neuropsychiatric testing administered by a neurologist, was diagnosed with autism. Laboratory results indicated nutritional insufficiencies, toxicities, immune abnormalities, and multiple food sensitivities. After four months of treatment with a hypoallergenic diet, nutrients, digestive enzymes, probiotics, oral chelation, hyperbaric oxygen, and Applied Behavior Analysis, the child’s mood improved, her speech returned and she regained social contact. Years later, her improvements were so profound that at a follow-up neurology visit, it was unbelievable to the physician that she had once presented with autism.
TY was 23 months old when she presented to the treating physician with a diagnosis of autism. When TY was 12-15 months old she had been given the varicella and MMR vaccines after which her parents reported she developed a rash, lethargy and dehydration. At 18-months-old, the next vaccine series was administered, including the combined tetanus, diphtheria, and pertussis, the inactivated polio vaccine, and the Haemophilus influenzae type b vaccine. The parents did not report using NSAIDs of any kind with the child. Almost immediately, the parents reported that TY lost speech, eye contact, and social contact. A pediatric neurologist diagnosed TY as autistic after a battery of neuropsychiatric testing and a physical examination. At the time of her first office visit, TY was irritable, made no eye contact and did not speak. She had chronic diarrhea and recurrent ear infections. TY displayed repetitive movements and self-injurious behavior. In articulating the gravity of her condition, her neurologist recommended a trust fund along with Applied Behavior Analysis (ABA).
A comprehensive battery of functional laboratory testing was ordered, including nutrient and toxic elements in erythrocyte, hair, and urine, urine organic acids, IgG food sensitivities, amino acids, glutathione and urine polypeptides. Routine labs were also ordered: a complete blood count, a metabolic panel with liver and thyroid function tests, and serum copper and zinc.
Figure 1. Erythrocyte nutrient elements measured were low and magnesium and zinc were very low. Calcium and heavy metals were normal in red cell (results not shown).
Figure 2. Urine elements were measured (A) before and (B) after provocation with DMSA. Pre-provocation results showed high nickel in urine (A). One month later post-provocation results showed high mercury, cadmium, and nickel (B).
Figure 3. Toxic elements in hair revealed high levels of chromium, cobalt, barium, manganese, bismuth, antimony, aluminum, germanium, and titanium.
Figure 4. Plasma amino acids were high-normal (5th quintile) and high (>95th%).
Figure 5. Markers of energy production were high-normal (5th quintile) and high (>95th%) in TY’s urine and suggested possible mitochondrial dysfunction.
Figure 6. Neurotransmitters and dysbiosis markers for TY.
Table 1. Multiple urine polypeptides were high, indicating leaky gut.
|Result||Status||Expected Range (ug/mg Cr)|
|Casomorphin (1-8) bovine||5.00||High||None detected- 1.75|
|Des-tyr casomorphin||29.59||High||None detected- 13.7|
Table 2. TY had high serum copper.
|Copper, Serum||161||High||70-155 ug/dL|
|Zinc, Plasma or Serum||94||Normal||70-150 ug/dL|
- Autism spectrum disorder
- Intestinal hyperpermeability
- High amino acids
- Low RBC nutrient elements
- Abnormal zinc:copper ratio
- High heavy metals: nickel, mercury, cadmium
- Low glutathione
- Cellular energy/mitochondrial dysfunction
- Low neurotransmitter turnover
- IgG antibodies to dairy, gluten containing grains, sunflower and brewer’s yeast
- Gluten-free/casein-free, removed sunflower and brewer’s yeast
- Multi-vitamin-mineral as directed
- Zinc, 25 mg/d
- EPA/DHA, 1 g/d
- Cod Liver oil, 1 tsp/d
- Trimethyl glycine (125 mg/d) and folinic acid (400 mcg/d)
- Amino acid formula of 20 essential and non-essential amino acids (1-2 g/day)
- Digestive enzymes, 1 cap before meals
- Probiotics 1 cap/d
- A fruit and vegetable whole food supplement, 6 chewables/d
- Topical magnesium sulfate cream (once daily) or magnesium sulfate baths (once weekly)
- Chelation protocol
- Oral DMSA was given to chelate heavy metals: 10 mg DMSA/kg body weight, three times daily, 3 days on, 11 days off, for approximately 3 months.
- Hyperbaric oxygen therapy was prescribed 4 times a week for 10 weeks.
- Applied Behavior Analysis was initiated
- One Month Follow-Up
Immediately after the first hyperbaric oxygen treatment, TY was using words again. Within one month of treatment, TY’s mood improved. Her parents were amazed. TY had begun using single words and making better eye contact. The physician noted in TY’s chart, “there is a good chance that she will be out of the autism spectrum in 6-8 months.”
- Four Month Follow-Up
After roughly four months of treatment, TY was no longer autistic. She was socially engaging. She had good articulation and some speech. She was processing well. There was complete resolution of presenting complaints.
Follow-up Laboratory Results
- One year after the first visit, the physician ran a blood zinc level. Two and a half years after the first visit, a urinary organic acids test was ordered. Due to the dramatic and rapid improvement, no other lab tests were ordered.
Figure 7. Neurotransmitter catabolites and quinolinate normalized in urine.
Figure 8. Bacterial and fungal markers in urine were still elevated for TY two and a half years later.
- Dysbiosis, especially Candida sp. overgrowth
- CoQ10 insufficiency
- Changed the digestive enzyme to one containing dipeptidyl peptidase IV
- Molybdenum 100 mcg/day
- Element supplement
- EPA and DHA
- Glutathione cream
- Discontinue amino acids
Follow-up Clinical Outcome
TY’s father e-mailed the physician almost four years after their first office visit. He said TY had been taken to another neurologist who remarked that she was as typical as any child that he had seen. He could not believe that she had been diagnosed autistic in the past.
DISCUSSION AND CONCLUSION
The prevalence of autism has dramatically increased in the past decades in the US and elsewhere.1 There was a 57% average increase in the prevalence of ASD from 2002 to 2006 and prevalence for boys was four to five times higher than girls.2 In 2007, one out of 91 children (ages 3-17) had the diagnosis of autism, and in 2016, CDC reported that 1 in 68 children have ASD (1 in 42 boys and 1 in 189 girls). These data are unchanged from 2014.3 Because of the great emotional and medical care costs for people with autism, integrative medical approaches that correct nutritional, metabolic, immunological, and detoxification abnormalities may hold promise for certain cases of childhood autism. TY is an example of a child who benefited from this approach.
TY initially showed very low nutrient elements in erythrocyte (Figure 1) and elevated toxic elements in hair and provoked urine challenge (Figures 2 and 3). While either low nutrient elements or high toxic elements by themselves can create symptoms, in combination, the effects of toxic elements can be greater when nutrient elements are absent.4,5 Since TY was only 23 months old at the time of testing, it may be that she accumulated heavy metals from her mother during fetal development.
She also had low reduced glutathione levels (result was 29; range was >32 mg/dL). Low reduced glutathione, an antioxidant and endogenous heavy metal chelator, could have been an additional disadvantage for TY, as it is required for conjugation and elimination of toxic metals. Low reduced glutathione has been demonstrated in ASD individuals 6 and may in part be related to genetic mutations in sulfuration and methylation pathway enzymes.7
It seemed that TY struggled with maintaining normal copper and zinc blood levels and a low zinc: copper ratio has been observed in children with autism spectrum disorder.8 At the time of her first visit, TY had low red cell zinc, normal red cell copper (Figure 1), and high serum copper levels (Table 2). Zinc (plasma or serum) was measured one year after her initial office visit and was low (result was 68; range was 70-150 mg/dL). The physician administered molybdenum to help reduce the high copper levels. Chelation of heavy metals with DMSA could have further depleted TY’s zinc levels and highlight the importance of repletion of nutrient elements when chelating toxic elements.
TY showed an unusual pattern of high and high-normal plasma amino acids (Figure 4). The clinician interpreted the high amino acid levels as poor utilization rather than excess total body status and prescribed an amino acid formula. The clinician also administered element cofactors, especially magnesium, to help TY’s tissues take up and metabolize the amino acids. Despite high levels of plasma aminos, markers of the neurotransmitter products such as norepinephrine, epinephrine, and serotonin, were low (Figure 6). Low vanilmandelate and low 5-hydroxyindoleacetate suggested poor neurotransmitter turnover while high quinolinate suggested an inflammatory response.
Amino acids together with a high quality multi-vitamin-mineral were prescribed to improve neurotransmitter production, thereby beneficially affecting TY’s neurological symptoms. As expected, TY experienced clinical improvement with treatment and neurotransmitters normalized on follow-up laboratory tests two and a half years later. Vanilmandelate and 5-hydroxyindoleacetate had increased, and quinolinate was within normal limits (Figure 7). The diagnosis of ASD was retracted for TY after less than one year of treatment.
TY showed moderate food antibodies (+3 and +4) to dairy products, gluten and mild reactions (+1) to sunflower and brewers’ yeast. Further, her urine polypeptides were abnormally high (Table 1). Elevation of these neuroactive dietary peptides is indicative of intestinal permeability9 and these urine peptides have been associated with ASD neurological and gastrointestinal symptomology. With mixed results, specific elevation of Indolyl-3-acrylolyglycine has been associated with ASD and has been recommended as a diagnostic indicator.10,11
ASD has been characterized by gastroenteropathy.12-15 Markers of bacterial and fungal overgrowth were high at the time of TY’s first office visit (Figure 6). Two and a half years later, bacterial and fungal metabolites were still elevated, suggesting that TY’s GI tract still had an imbalance in microflora (Figure 8). TY had a high level of D-arabinitol, suggesting Candida colonization in the small intestine. Despite clinical improvement, continued attention was needed to restore TY’s intestinal barrier, balance the microbial populations, and modulate the immune response. Because this organ system was still imbalanced after clinical improvement, it is fair to assume that gut dysbiosis may have been a critical antecedent to her presenting condition. Gut dysbiosis, urine peptides, and IgG antibodies to dairy may have explained TY’s presenting complaints of diarrhea and recurrent ear infections.
High urinary quinolinate also suggested an inflammatory process, usually brought on by virus, parasites, bacteria, or fungi. This excitatory neurotransmitter binds the glutamate receptor, NMDA. High levels of glutamic acid stimulation of the glutamate receptor system (including NMDA) has been shown to have negative effects on brain development and maturation and this excitotoxicity has been suggested as one possible mechanism in autistic pathophysiology.16,17 It has been hypothesized that infection, leading to increased quinolinate, may affect neural development in autism spectrum disorders. 17 Magnesium would have blocked the binding of quinolinate to NMDA receptors in the brain, contributing to less neurotoxicity. Based on TY’s tests and history, possible causes of the increased quinolinate were small intestinal dysbiosis and the vaccines she was given prior to regression. Quinolinate was normal two and a half years after her initial visit.
TY showed evidence of disturbances of cellular energy metabolism, with elevations of ethylmalonate, lactate, and pyruvate along with other markers of mitochondrial function such as a-ketoglutarate and hydroxymethylglutarate (Figure 5). Organic acid markers of mitochondrial function showed TY likely had an ATP deficit and had insufficient intake of Coenzyme Q10, B-complex, and carnitine. Follow-up testing two and a half years later showed that organic acid markers normalized, including ethylmalonate, pyruvate, a-ketoglutarate, and hydroxymethylglutarate. However, she did show a very high malate which suggested continued need for CoQ10. P-hydroxyphenyllactate, a marker of oxidative damage and unregulated cell division, was normalized upon retest.
TY’s initial presentation with reduced speech, eye contact, and social contact, irritability, repetitive movements and self-injurious behavior may have been a result of many factors. TY’s laboratory tests demonstrated dysbiosis, intestinal permeability, food sensitivities, heavy metal toxicity, and nutritional insufficiency (elements and amino acids), mitochondrial dysfunction, and poor neurotransmitter synthesis. After four months of treatment with an allergen-free diet, nutrients, digestive enzymes, probiotics, chelation, hyperbaric oxygen18,19, and ABA, TY’s mood improved. Her speech returned and she regained social contact. Years later it was unbelievable to her neurologist that she had ever had the diagnosis of autism.
A statement from the Institute of Functional Medicine:
IFM’s medical education supports the use of vaccinations. Vaccinations against a variety of diseases have been a critically important step forward in medical science. Vaccines have been studied extensively, and while continued critical evaluation and discussion about all medical treatments is the way science moves forward, vaccination administration is an important standard of care that is supported by IFM.
- Kogan MD, Blumberg SJ, Schieve LA, et al. Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics. Nov 2009;124(5):1395-1403.
- Counting Autism. National Center on Birth Defects and Developmental Disabilities http://www.cdc.gov/ncbddd/features/counting-autism.html. Accessed 1/14/10, 2010.
- CDC. CDC estimates 1 in 68 school-aged children have autism; no change from previous estimate. 2016; https://www.cdc.gov/media/releases/2016/p0331-children-autism.html. Accessed 08/2017, 2017.
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- Ohta H, Cherian MG. The influence of nutritional deficiencies on gastrointestinal uptake of cadmium and cadmium-metallothionein in rats. Toxicology. 1995;97(1-3):71-80.
- James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. Dec 2004;80(6):1611-1617.
- James SJ, Melnyk S, Jernigan S, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. Dec 5 2006;141B(8):947-956.
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- Bull G, Shattock P, Whiteley P, et al. Indolyl-3-acryloylglycine (IAG) is a putative diagnostic urinary marker for autism spectrum disorders. Med Sci Monit. Oct 2003;9(10):CR422-425.
- Wright B, Brzozowski AM, Calvert E, et al. Is the presence of urinary indolyl-3-acryloylglycine associated with autism spectrum disorder? Developmental medicine and child neurology. Mar 2005;47(3):190-192.
- Luna RA, Oezguen N, Balderas M, et al. Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder. Cellular and molecular gastroenterology and hepatology. Mar 2017;3(2):218-230.
- Iovene MR, Bombace F, Maresca R, et al. Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders. Mycopathologia. Apr 2017;182(3-4):349-363.
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- Bransfield RC, Wulfman JS, Harvey WT, Usman AI. The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders. Med Hypotheses. 2008;70(5):967-974.
- Rossignol DA, Bradstreet JJ, Van Dyke K, et al. Hyperbaric oxygen treatment in autism spectrum disorders. Medical gas research. Jun 15 2012;2(1):16.
- Rossignol DA, Rossignol LW, Smith S, et al. Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial. BMC pediatrics. Mar 13 2009;9:21.