A Biomedical Approach Via Telemedicine in the Treatment of a Child With Sensory Processing Disorder Using Diet and High-dose Biotin Intervention: A Case Report

Abstract

Background

We present the case of a 6-y-old boy who was diagnosed with sensory processing disorder with developmental language and learning delay. He was treated successfully with diet and high-dose biotin along with other nutrient support that resulted in resolution of abnormal sensory behaviors and improvement in language and learning.

Case/Intervention

The child was diagnosed with a presumed biotin deficiency from organic acids testing which revealed markers that reflected biotin deficiency despite supplementation with 300 mcg daily (AI = 12 mcg/d). Stool markers were also noted for low beneficial biotin producing microbiota. In the course of several months of high-dose biotin supplementation with herbal treatment for dysbiosis, he was able to subsequently transition from special needs classes requiring sensory support into mainstream classes as a neurotypical child with age appropriate language and learning skills and resolution of abnormal sensory behaviors.

Conclusion

This case illustrates the importance of using functional nutrition labs to rule out nutrient imbalances that could be a cause of improper signaling in the brain, which can translate into delayed language, learning, and behavior disorders. Organic acids may reveal a much higher level of need of nutrients, especially when polymorphisms of enzymes are present that may be responsive, as this case demonstrates, to targeted high-dose nutrient therapy.

This case reports a child with sensory processing disorder (SPD), one of the most common behavioral traits seen in autism spectrum disorder (ASD) that is characterized by either an overresponse or underresponse to stimuli and can be explained as a dysfunction of the inhibition/excitation balance in the central nervous system in ASD.¹ This child was found to have laboratory biomarkers of biotin deficiency through nutritional testing. High-dose biotin resulted in significant improvements in SPD including improved behavior, language skills, energy levels, and academic performance.

Biotin is a B vitamin that plays a critical role in carbohydrate metabolism and fatty acid synthesis, and it also acts as a cofactor for many enzymatic reactions. It is produced endogenously by the gut microbiome, specifically bifidobacteria, and is also obtained from foods such as egg yolks, liver, and yeast. Inadequate biotin levels can lead to disorders of the nervous system, disordered carbohydrate and energy metabolism, and insulin resistance. This case was written following the CARE guidelines.²

Initial Nutritional Consult

The patient was a 6-year-old Caucasian boy living in Australia, whose mother requested a telemedicine nutritional consultation. She reported that the child had delayed learning, frequent migraines with aura, and energy crashes in the afternoon that interfered with school attendance. He had sensory issues that caused a spinning behavior, he would stand on his head while watching television, and he would “sniff” people who came near him. He followed a gluten-free diet but craved carbohydrates and processed foods while rejecting many textured foods, fruits, and vegetables. He had difficulty falling asleep and enuresis contributing to insomnia.

Timeline.

Relevant History

He had been born vaginally and was breastfed until age 7 months. He had gastrointestinal issues dating back almost to birth (2010), and subsequently he developed gastroesophageal reflux disease and eczema at 4 months of age and was prescribed ranitidine. He developed normally until approximately 12 months of age. At this point, his speech became unintelligible, he became more emotionally liable, and he acquired more frequent illnesses. His behavior continued to deteriorate during the next 2 years. At age 4 years, genetic testing revealed a compound heterozygous genetic polymorphism of MTHFR C677t and A1298c. At this time, he was also diagnosed with pyrrole disorder, at which time the mother elected to implement a gluten-free diet. When gluten was rechallenged for 1 day after several weeks of being gluten free, he became nearly nonverbal, avoided eye contact, and had cognitive decline that lasted 1 week. He has been gluten free ever since.

At age 5 years, he was diagnosed with SPD and speech apraxia by an occupational therapist. His naturopathic doctor recommended stopping vaccination, because he was due for his second MMR follow-up shot. He has not been vaccinated since.

In the fall of 2015, he began having allergy symptoms and additional cognitive decline after the family moved into a rental home that was subsequently found to be contaminated with diesel fuel. They moved again a few months later. His physician ordered a stool test in January 2016 (Table 1) that showed an overgrowth of Streptococcus and Clostridium species with corresponding low beneficial bacterial growth of lactobacillus and bifidobacteria. The imbalanced bacteria were treated with pulse dose erythromycin antibiotics (1 week on and 1week off) and a biofilm protocol with apple pectin.

Table 1.

Bioscreen Stool Test: The Abnormal Results Before Intervention

Test	Results	High Low	Normal Range
Total aerobe count	1.25 × 109	Hi	1.00 × 107 to 1.00 × 108
Streptococcus (total)	6.10 × 107	Hi	<3.00 × 105
Streptococcus salivarius	5.98 × 107
Streptococcus parasanguinis	1.14 × 106
Total anaerobe count	3.85 × 1010		1.00 × 106 to 1.00 × 1012
Eubacterium (total)	<9.00 × 107	Low	1.00 × 108 to 1.00 × 109
Lactobacillus (total)	<5.00 × 105	Low	5.00 × 106 to 1.00 × 107
Clostridium (total)	6.35 × 109	Hi	<5.00 × 106
Sutterella wadsworthensis	1.27 × 109	Hi

He was also placed on digestive enzymes and oxbile, after which the mother reported that he showed improvements in speech and in bowel movements. However, the child acquired a secondary Staphylococcus skin infection during antibiotic therapy that was treated with natural therapies. In June 2016, he was diagnosed with Dientamoeba fragilis and placed on seconidazole, nitazoxanide, and furazolidone, but these were discontinued after 5 days due to a lack of tolerance.

In July 2016, the mother reviewed her son’s medication and supplementations with a pharmacist/CNS via telemedicine to search for alternatives to his current treatments (Table 2) prescribed by his 3 physicians (an integrative MD, a naturopath, and a neurologist) and occupational therapist. He attended preschool, and received sensory supports-wiggle wedge, nap time, and early dismissal as needed. He was participating in taekwondo twice weekly and soccer once per week; however, his mother reported that he had “low energy.” A nutritional evaluation with a laboratory test—NutrEval by Genova Diagnostics (Asheville, NC, USA)—was ordered prior to his first nutritional consultation and the results were sent electronically to the remote pharmacist/CNS.

Table 2.

List of Supplements Taken by the Child Before Intervention

Omega 3 s		NAC
P5P	33.8 mg	Selenomethionine	600 mg
Hydroxy B12	1000 mg	Molybdenum	5 mcg
5-MTHF	500 mcg	Lithium orotate	50 mcg
Phosphytidylcholine	420 mg	Enzymes	5 mg
Mag-L-threonate	48 mg	Oxbile (BID)	BID
Biotin	300 mcg	Vitamin C	125 mg
Zinc pic	30 mg	Galactomune	500 mg
Vitamin E	200 IU	Flora Restore	Prebiotic
Melatonin (hs)	1 mg	Ultra Flora	Probiotic
Acetyl-L-carnitine	250 mg

Diagnostic Assessment

We reviewed the results of the NutrEval (July 2016) with the hope that it would provide new information that would help her son’s behavior improve and help him assimilate into regular mainstream classes with full-time attendance. The results of the NutrEval suggested a biotin deficiency with elevated 3-hydroxyisovaleric acid (Table 3). There were elevations in other organic acids: 3-hydroxyproprionic acid, isovalrylglycine, beta-hydroxybuteric acid, alpha-ketoglutaric acid, and malic acid. In addition, the amino acid lysine was low (which was consistent with the biotin deficiency). The nutritional diagnosis was that his episodes of “low energy,” carbohydrate cravings, and SPD were related to a biotin deficiency, and that by optimizing biotin levels many of his symptoms would improve.

Table 3.

NutrEval: The Abnormal Results, July 2016

Antioxidants	Results
α-Lipoic Acid	Borderline Low
Organic Acids Metabolites	Results (Mcg Mol/mol creatinine)	95% Reference Range
Metabolic Analysis Markers (Urine)
β-OH-butyric acid	3.7	≤3.4
α-Ketoglutaric acid	190	12 to 55
Isovalrylglycine	3.1	≤5.4
3-Hydroxyproprionic	17	6 to 23
3-Hydroxyisovaleric	37	≤38
Amino Acids (Urine FMV)	Results (Mcg Mol/mol creatinine)	95% Reference Range
Lysine	116	64 to 507
Blood: Li HEPA	Results (nmol/L)	Range
Glutathione, reduced	4.1	3.8 to 5.5
Glutathione, oxidized	0.42	0.16 to 0.5
RBC Fatty Acids	Results (%)	Reference Range
Monounsaturated fats, total	23.62 (High)	7.5 to 17.9
Omega 3—α-linoleic acid	0.25% (High)	0.1 to 0.2
Eicosapentaenoic acid	1.88% (High)	0.1 to 0.2
Omega 6—linoleic	13.84% (High)	5 to 12.4
Monounsaturated: palmitoleic acid	0.83% (High)	0.0 to 0.4
Monounsaturated: oleic acid	21.71% (High)	7.5 to 15.5
Total monounsaturated fats	23.63% (High)	7.5 to 17.9
Total omega-9 fatty acids	22.79% (High)	16 to 20.6

Therapeutic Recommendations

The recommendation was to begin by increasing biotin from 300 mcg to 4000 mcg (4 mg) daily, then every 3 days to add the following in this order: lysine 1000 mg in 2 divided doses daily, vitamin B₅ (pantothenic acid) 250 mg daily, lipoic acid 100 mg daily, low-dose niacin 25 mg daily and PRN for anxiety, then, last, ImmunoThrive. The mother was also instructed to increase biotin by 1 mg every week as tolerated up to 10 mg daily dosing. The mother reported that many of his sensory issues improved and the spinning stopped completely by day 3 of biotin supplementation. Within 2 weeks of following the suggested protocol, he was accepting many more fruits and vegetables in his diet, he started sitting upright while watching television, and he was no longer “sniffing” people. His headaches went away completely after starting the Immunothrive supplement.

Consultation 2

At the second consultation in August 2016, we reviewed the fatty acid portion of the NutrEval. The fatty acid patterns revealed low glutathione recycling and high monounsaturated fats (Table 3). The recommendation was made to lower sugar intake and to eat more fruits, berries, and palm oil, and add 1 capsule of berberine, 350 mg, daily. Following these nutritional recommendations, the mother reported an improvement in sentence formation, fine motor skills, short-term memory and sustained learning.

The patient followed up with his physician in September 2016, and it was recommended to discontinue biotin for 10 days so that a repeat thyroid panel could be performed, because biotin supplementation can interfere with test results. Biotin was stopped and sensory issues immediately returned with occasional spinning behavior. However, once biotin was restarted, the sensory issues quickly resolved.

Follow-up

The mother contacted the pharmacist/CNS the following December 2016 to provide an update on her son. She was elated that his progress had exceeded learning expectations at school. He was able to count to 200, which far surpassed the initial goal of counting to 20. He was also able to follow directions from his teacher and was performing at an age-appropriate level. He actively participated in the school Christmas program without incidence, despite the presence of loud music and being surrounded by many unfamiliar adults. In February 2017, it was recommended by his preschool teacher that he be advanced from special needs half-day classes into mainstream all-day classes.

Discussion

SPD is a condition in which the brain has difficulty in processing external stimuli that comes in through one of the 7 senses and relays the information to other parts of the brain for a proper response. This condition is typically associated with ASD, and in children, may be characterized by rejection of textured foods or repetitive behaviors, failure to respond to stimuli, or even emotional liability when exposed to unfamiliar people or in situations in which they feel overloaded with sensory information. The current conventional treatment is multidisciplinary which includes enrolling the child in applied behavior therapy, speech therapy, occupational therapy, social skills training, providing a controlled sensory environment, and/or counseling.³ Incorporating a functional nutritional approach that can rule out nutrient imbalances as a root cause of abnormal behaviors can complement behavior therapy and training enhancing the lives of the children and their families.

Patient Perspective.

“Before we contacted the nutritionist for help, we were completely focused on our son’s behaviors and symptoms and worried about how much they were impacting his life, the functioning of our family, and what type of future he would be able to have. The treatment protocol set forth by the nutritionist has had a tremendous impact in improved behavior and functioning. We now have hope for a normal life for him and the stress on the family has been significantly reduced.”

This case demonstrated that by using the NutrEval functional lab testing, nutrient deficiencies, and genetically weak enzyme pathways may be uncovered and subsequently corrected by targeted nutrient therapy. It also emphasizes the benefits of being able to access a highly trained professional in the analysis of organic acids via telemedicine who can offer this type of expertise to individuals on a global scale that may not have access otherwise.

Our patient received significant dietary and supplemental support as prescribed by his 3 physicians and his occupational therapist. However, the nutritional testing reveled a much higher need for biotin than what was previously administered, even though the daily AI dosing recommendation had been met. The human body is incapable of synthesizing biotin and is dependent on what we get from food sources and from what our gut microbes manufacture for us, especially from the bifidobacteria species which can be disrupted by antibiotic use, poor dietary choices, and even advanced aging or illness. We also depend on biotin to be recycled in the body by the biotinidase enzyme.⁴ A deficiency can be due to low intake of foods that contain biotin, problems with the transporting and absorption of biotin from the gut, low beneficial biotin producing bacteria, a defect in recycling, and even from an increased need due to a weak enzyme system that would require a much higher intake to drive the biotin dependent pathways forward. The marker, 3-hydroxyisovaleric is a sensitive and specific marker for biotin and will be elevated in the urine in deficient states.⁴

The exact nature of the cause of SPD is not completely known or understood, but biotin was singled out in this case even though it appeared to be only borderline deficient despite other markers indicating high need for other nutrients because it was closely correlated with the symptoms of this child: carbohydrate cravings, spinning behavior (which could indicate poor fatty acid balance in the brain), and energy crashes (Table 3). Biotin is a cofactor in several important enzyme reactions and a deficiency can present as neurological disorders, lethargy, reduced muscle tone, skin eruptions, frequent infections, and even psychosis or death if left untreated.^6,7

The patient described in this case presented with neurological sequela that was consistent with biotin deficiency. A block in pathways due to insufficient biotin as a cofactor can affect glucose regulation in the liver and cause carbohydrate cravings due to the inability to undergo glucose synthesis when needed. It can also cause a decreased synthesis of longer chained fatty acids that are needed for brain health and proper communication causing sensory or inappropriate signaling in the central nervous system affecting behavior and cause mood disorders. Emotional liability can be caused by the accumulation of branch chain amino acids due to the inability to metabolize them, which in turn, may affect the neurotransmitter balance, since the branch chained amino acids help to regulate neurotransmitters in the central nervous system.⁸

Metabolically, the body will attempt to compensate for the inability to synthesize glucose in the liver by increasing the conversion of glutamate to alpha-keto-glutarate, because this intermediate serves as a flux between the citric acid cycle that feeds into the gluconeogenic pathway to help with glucose homeostasis. This was evident by elevated alpha-keto-glutarate levels that was 4 times higher than the 95% reference interval. However, with a biotin deficiency, this attempt to maintain glucose homeostasis was futile as evidenced by elevated β-OH-Butyric Acid (BHBA), a marker indicating ketosis as the body converts acetyl-CoA to ketones to use as a backup energy source when glucose is in short supply.⁶ Due to the inability to use glucose with a biotin deficiency, the excess glucose will then be shunted to the triglyceride pathway and will result in high levels of saturated fatty acids as seen in this case (Table 3).⁹

The addition of lysine to the therapeutic regimen was to support the biotin transport in the bloodstream. In addition, biotinyllysine supports the binding of biotin to the carboxylase enzymes that are involved in glucose and fatty acid synthesis.¹⁰ Second, pantothenic acid supplementation was added to prevent a deficiency because biotin and pantothenic acid share the same transporter for absorption. A high-dose supplementation of 1 supplement could essentially cause a depletion and deficiency of the other.

The parents played an essential role in the recovery of their child from SPD. Their willingness to educate themselves on other options available to help their son was a vital part of his progress. They made dietary changes and kept track of a rigorous supplement protocol, which opened up new doors of opportunity for the improvement and assimilation of their son into society as a neurotypical child. It is important to note that not all children with SPD will respond in the same manner nor to the same nutrient as our case study. Using functional nutritional labs is a strategic way to explore and rule out nutrient imbalances as a contributing factor in all cases of SPD. It is our opinion that biotin was the key nutrient in recovering this child from severe SPD, but that the combination of diet and additional nutrient support and herbal treatment for dysbiosis further accelerated his improvements.

Conclusion

This is a compelling case for the use of telemedicine and of functional nutritional lab testing in treating SPD to identify the nutrients that may be contributing to sensory and behavioral issues as well as learning and developmental delays. Each case of SPD and ASD is unique and complex. Following a blanket treatment protocol is not appropriate in treating these cases, and an individualized approach should be managed by a professional that is trained in functional medicine with extensive knowledge of vitamins and minerals and their association with mood and behavioral disorders, as well as the analysis of organic acids. Addressing the root cause of a health issue with targeted nutrient therapy such as in our case with high dose biotin can restore metabolic pathways to normal, allowing the body to function properly again. An analysis of organic acids can be done remotely that can reveal significant information about the underlying biochemistry of an individual without requiring the physical presence of the patient. It is our belief that restoring homeostasis by using a functional medicine approach will allow healing to take place and the body will return to normal functioning on its own.

Additional strength of this case was the withholding of biotin for a short period while retesting thyroid labs with a return of behavior symptoms and occasional spinning. However, once the biotin was restarted, the behavior symptoms quickly resolved. Weaknesses in this case are the fact that this patient consulted with the pharmacist/CNS remotely and was not seen one-on-one in the clinic so a physical assessment was not done, and the lack of follow-up labs confirming the resolution of biotin deficiency, normalization of the alpha-keto-glutarate and BHBA ketosis markers, and with resolution of dysbiotic markers in the stool. These functional tests are not covered under the parent’s insurance plan in Australia, so the parents elected to accept the results of improved behavior, learning and restoration of proper energy levels as sufficient evidence for continuing to follow the biotin and supplement protocol laid out for them by the pharmacist/CNS. It was unknown whether the biotin deficiency was due to dysbiosis or due to enzyme deficiency or a combination of both. However, it was the suspicion of the pharmacist/CNS that the child had a deficiency in the holocarboxylase enzyme, as many times these cases can be contributed to polymorphisms in this enzyme that is highly responsive to high dose biotin therapy.¹¹

Biographies

Gail Clayton, RPh, MS, CNS

Heather A. Carrera, MS, CNS

Edward R. Martin, MBA, CFP, is in Bourne, Massachusetts.

Demetrice Morrison, MPH, MHA, RDN, LDN

Abubakar A. Bawazir, MS