In recent years, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have attracted attention [1]. These children often show sensory hypersensitivity, which may persist into adulthood, but the cause is still unknown [2]. Sensory hypersensitivity can lead to tantrums in school days, group activities or everyday life, resulting in acute loud crying or strange noises.

For pathophysiological aspect, various discussion for ASD has been found [3]. The category of Neurodevelopmental disorders (NDDs) include ASD, ADHD, cerebral palsy (CP) and intellectual disabilities. NDDs have association with altered Synaptic adhesion molecules (SAMs). SAMS consist of glycoproteins localized on the neuronal surfaces, which are primarily expressed at synaptic plasma membranes. Consequently, neurotoxic metals may contribute to the pathogenesis of NDDs, possibly through disruption of SAM.

The authors have been involved in the integrated medicine (IM) and clinical practice and research ASD for years [4,5]. Among them, to alleviate the hypersensitivity, an approach tailored to each individual is required [6]. In this study, we conducted music sessions with ASD child who experienced tantrums since infancy and his mother. Their sensory hypersensitivity improved, and we report the progress with some perspectives.

The patient: The client (Cl) was 7-year-old boy with ASD and intellectual disability, with 122 cm tall and weighed 22 kg. Complications included hay fever, vocal tics, and pruritus. Cl ate a gluten-free diet except for school lunches, and had small bowel movements every two days. Subjective symptoms included cough, runny nose, and itching. Psychologically, Cl was characterized by anxiety, and found interpersonal relationships difficult. During our music therapy sessions, Cl initially struggled to maintain concentration. When sitting on the piano stool, Cl would move his ankles restlessly and leave after a few minutes. Cl walked around with small instruments (bells, tambourines, maracas, etc.). Cl played percussion instruments (snare drum, bongos, xylophone) by slamming the plectrums against the instruments. When Cl held the recorder in his mouth, Cl inhaled instead of exhaling. In addition, two months after starting music therapy, Cl began taking supplements containing vitamins B₁, B₆, A, D, E, K, C, iron, zinc, selenium, Spectrumzyme (proteases, lipase), and uDHA micelles (oxygenated DHA, ferric acid).

The patient's mother (Mo) is 39-years-old, thin, without any regular medications. Mo has difficulty turning her neck and then Mo received acupuncture treatment. Mo frequently shout at their children and give him emphatic instructions during playing musical instruments [7] (Figure 1). Mo moved to send Cl to elementary school known for its inclusive education, and Mo lives apart from husband during weekdays. Mo has a psychological complex stressor about her husband's mother's impressive career [8]. Mo attended piano lessons in elementary school, but quit because she couldn't read bass clef music. During sessions, Mo was unable to wait Cl to think calmly.

Figure 1: Mother's pointing as over-intrusive behavior.

1) Music Therapy Sessions: Individual therapy was conducted three times a month, approximately 40 minutes per session, with the Cl and Mo. Activities included introductory song, piano playing, instrument playing, singing, and closing greeting.

The music therapist (MT) avoided verbal instructions to Cl as possible and respected his independent musical instrument activities [9]. The author accompanied the his speech and singing. To facilitate the visually impaired his understanding, picture-sound notation, colored notation, and colored cards were used (Figure 2). Recorder instruction was conducted in three stages: i) blowing into a recorder for tanning practice, ii) recognizing differences in notes using a recorder for fingering practice, and iii) learning the recorder used in elementary school (Figure 3).

The mother played the piano with the MT using sheet music in treble clef only. Mo practiced breathing techniques with the MT at the breaks between phrases. Even when Mo made mistakes or lost rhythm, the MT never immediately corrected her. "It's okay," I gently assured her, waiting until Cl could think for himself and play correctly.

2) Oligoscan: It scans the palm of the hand with a special device without taking blood, urine, or hair samples [10] (Figure 4). It can painlessly measure the accumulation of 21 essential and reference minerals and 16 toxic heavy metals within a few minutes.

3) Evaluation Method: Changes in concentration evaluated by family members and Oligoscan test results provided by family members were used [11].

Figure 2: picture-sound notation.

Figure 3: Three types of recorder.

Figure 4: Oligoscan apparatus for Spectrophotometry.

1) Behavioral and psychological changes: After the 10th session (3 months), CL's tantrums clearly decreased, and Mo's mental distress was alleviated. Cl could play the piano until the end of the song with looking at the colored note music. After repeated tanning practice on the recorder, Cl can play the correct note and rhythm without walking around. Cl maintained his concentration when playing music. After about 20th session (6-7 months), his hard stools has changed to normal sausage-shaped stools every day. From around the 30th session (10 months), his skin pruritus improved, and the itching disappeared during sessions, singing, and playing an instrument.

2) Oligoscan evaluation: The results of spectrophotometric analysis are summarized (Figure 5) [12]. They are i) the results of the mineral and toxic heavy metal tests were generally around the normal range, ii) the cause of the high iodine levels is unclear and the patient will be monitored, iii) the usual supplements will be continued, and iv) the mineral balance improved 11 months after music therapy compared to 4 months after, where improvement from low to normal for zinc/magnesium/phosphorus, persisting high for iodine, and persisting low for silicon and chromium.

Figure 5: Result of for Spectrophotometry in the case.

In this study, music therapy was performed on ASD Cl and Mo, resulting in improvements in their musical skills. Developmental disorders are characterized by difficulty understanding abstract instructions, tacit understanding, metaphorical expressions, sarcasm, and jokes [13]. During music therapy sessions, MT confirmed that Cl pays attention to MT, and then provided concrete expressions and visual information. Furthermore, his accumulated experience of self-determination during the sessions contributed to the improvement of musical skills. During the sessions, various symptoms associated with sensory hypersensitivity were alleviated, suggesting clinical effect. The Cl and MT continued to engage in "musical play," building a trusting relationship. Through singing and musical instrument performances, Cl, Mo and MT shared and empathized with music, which may gradually improve autonomic nervous function [14]. However, symptoms such as sneezing, runny nose, and itching remained unchanged. Among subjective symptoms, only anxiety had improved 18 months after starting sessions.

In previous metallomics study (1,967 ASD children, 0-15 years, M/F=1,553/414), analysis of 26 trace elements in hair revealed zinc deficiency 29.7% and magnesium deficiency 17.6% [15]. As recent study for 2550 ASD (M/F 2108/442, aged 0-15), about one-half infantile aged 0-3 years showed zinc deficiency and toxic metal burdens including iron and molybdenum. Then, various mineral imbalances may play principal certain roles for occurring neurodevelopmental disorders [16]. As developing technique, 28 kinds of essential elements and heavy metals can be measured in the hair of the children [17]. A cross-sectional study was performed in the Mediterranean region for analyzing 419 children hair aged 3-12 years. From these, each standard range can be taken contributing fundamental value worldwide.

The latest review showed the role of trace elements (TEs), macro elements (MEs) and ultra-trace elements (UTEs) [18]. ASD child tends to have high concentrations of chromium (Cr), arsenic (As) and aluminium (Al). Toxic metals such as aluminum (Al) are responsible for problems of socialization and language skills. Zinc (Zn) and copper (Cu) are important for regulating gene expression of metallothioneins (MTs). ASD often have zinc deficiency and copper excess. Higher copper (Cu) and manganese (Mn) are characteristic for ASD. ASD child shows urinary reduction of lead and cadmium, while they show higher urinary chromium (Cr). Higher values of arsenic (As) and mercury (Hg) are observed in the blood of ASD child. The metallomics study for 2550 ACD children aged 0-15 years was conducted for trace elements. As a result, 921(36.1%) showed elevated molybdenum concentration. For infants aged 0-3years, high molybdenum level was found for 54.0% for boy, and 62.6% for girl. A high significant inverse relationship was present between zinc and molybdenum concentration (r = - 0.510, p < 0.0001) [19].

Another study included 124 ASD children and 57 control, where trace elements and heavy metals were measured from hair samples by inductively coupled plasma mass spectrometry (ICP-MS) [20]. As a result, children with severe ASD revealed significantly higher values of trace elements for copper (Cu), and heavy metals for vanadium (V), cobalt (Co), nickel (Ni), arsenic (As), cadmium (Cd), and lead (Pb) in comparison with the control. For the relationship between zinc and ASD occurrence, systematic reviews and meta-analyses were conducted [21]. Totally 25 studies including 4763 cases were studied. Blood zinc levels showed negative association with ASD by standardized mean difference [SMD]?=?−0.44. For recent report, 194 ASD children were studied for brain magnetic resonance imaging (MRI) and trace elements [22]. They showed high concentration of vanadium, rubidium, thallium, and silver, and lower magnesium correlated with brain indexes.

Few reports on ACD and iodine/thyroid function were found. Polish boys with severe ASD (n=40) were evaluated for iodine status, hormone values and individual symptoms by Childhood Autism Rating Scale (CARS) [23]. Among them, 19 cases showed mild to moderate iodine deficiency. Further, lower urinary iodine, fT3 and fT4, and higher TSH levels were found compared with control. As another report, maternal exposure to thyroid disrupting factors during pregnancy could elevate ASD probability [24]. Japanese people are known to have high iodine value due to consuming seaweed habit.

Meanwhile, the sessions reduced the mother's neck pain and corrected her forward-leaning posture when playing the piano. The mother's over-interfering behavior during the sessions decreased, but immediately after the session ended, she would loudly tell him to "hurry up" [25]. The improvements to the mother's physical and mental fatigue and stress may lead to improvements in sensory hypersensitivity symptoms.

Some limitation may exist for this report. There are various probable complex etiologies for the onset and development of ASD. Both environmental and genetic factors may be involved in clinical symptom, sign and medical progress of this case. We will follow up the cases with careful attention.

In summary, two cases of Cl and Mo were studied from MT and spectrophotometry points of view. MT session contributed relieving the symptoms, and the spectrophotometric research will be continued for further evaluation. We hope that this report will become useful reference for integrative medicine (IM) in the future.

Conflict of interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

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