Abstract
Background
Scurvy has re-emerged in association with neurodevelopmental and eating disorders, particularly selective eating. This study aimed to investigate the clinical characteristics of pediatric scurvy cases.
Methods
We retrospectively assessed the data of pediatric patients diagnosed with scurvy at a Japanese medical institution between 2017 and 2023. Clinical characteristics, nutritional profiles, and treatment outcomes were analyzed.
Results
In total, 13 children, median age 52 months, had scurvy, 92% of whom had confirmed or suspected autism spectrum disorder; all were diagnosed with an eating disorder. All children also had low serum vitamin C levels, and 85% exhibited multiple nutrient deficiencies. Common symptoms included gait disturbances (85%), joint pain (69%), and fever (46%). Eight patients (62%) were misdiagnosed by their previous doctor. In the acute phase, the median symptom resolution time was 10 days by administration of vitamin C. In the chronic phase, despite nutritional counseling and education, none of the patients were able to consume enough vitamin C by food, and the prescribed vitamin formulation was not taken in 4 of 9 patients (44%) owing to hypersensitivity. Treatment with odorless, tasteless, multiple-micronutrient supplements containing vitamin C was successful in all 11 patients who attempted it.
Conclusions
All cases of pediatric scurvy in this cohort were caused by an eating disorder, neurodevelopmental disorder, physical disease, or a combination thereof. The diverse clinical course and misdiagnosis in some cases underscore the importance of a detailed dietary history for diagnosis. In terms of treatment, all patients in this study had very limited oral food owing to autism, but none required tube feeding, indicating that tasteless, odorless, multiple-micronutrient supplement powders might be beneficial in reducing the need for tube feeding in children who cannot take the prescribed vitamin formulation orally.
Keywords: Autism spectrum disorder, Scurvy, Eating disorders, Complementary feeding, Vitamin C
Background
Scurvy is caused by vitamin C deficiency. Vitamin C is involved in the synthesis of collagen and chondroitin sulfate; however, humans are unable to synthesize it endogenously [1]. Vitamin C deficiency results in the impairment of interstitial collagen and dentin, causing subcutaneous hemorrhage, mucosal bleeding, and subperiosteal hemorrhage [2]. Compared to other nutritional deficiencies in children, scurvy is rare, and its non-specific symptoms involving the musculoskeletal system, skin, teeth, and systemic manifestations often result in delayed diagnosis [2]. Typically, symptoms respond rapidly to vitamin C administration. However, delays in diagnosis and treatment can occasionally be fatal, with reported deaths due to infections, intracerebral hemorrhage, and cardiac tamponade [3–5].
In developed countries with improved nutritional environments, scurvy in otherwise healthy children is considered rare. Recently, however, reports of scurvy in children with abnormal eating habits or underlying diseases have been increasing, even in developed countries, and scurvy is an important psychosocial problem in children. A review of studies published over the past 20 years suggested that children with autism spectrum disorder (ASD), eating disorders, end-stage renal disease requiring dialysis, and gastrointestinal malabsorption disorders are at a higher risk for scurvy [2]. To the best of our knowledge, epidemiological reports on scurvy in Japan have not yet been documented. The treatment involves vitamin C supplementation via oral administration, intravenous injections, or dietary adjustments. However, the treatment of malnutrition associated with eating disorders can present significant challenges, and oral intake is frequently impeded by factors such as taste, smell, and texture, often necessitating tube feeding. After it is initiated, patients may undergo months to years of therapy to wean them off tube feeding [6, 7]. In recent years, there have been reports of the treatment of children with eating disorders and nutritional deficiencies with supplemental nutritional supplements instead of tube feeding [8], but the clinical characteristics of patients with eating disorders are not known. Therefore, in this study, we aimed to investigate the clinical characteristics of children with scurvy.
Methods
In this retrospective study, we included patients diagnosed with scurvy at Hyogo Prefectural Kobe Children’s Hospital between January 2017 and December 2023. Scurvy was defined as patients who presented with a serum vitamin C level below 2 µg/mL or dietary history that suggested vitamin C deficiency and were diagnosed with scurvy by the attending physician. An electronic medical record system was used to identify target patients; no patients were excluded. For each patient, we collected information on age, sex, height standard deviation score (SDS), body mass index (BMI) SDS, underlying diseases, diagnosis of eating disorders, diagnosis by previous physicians, duration from onset to diagnosis, symptoms, clinical test results at diagnosis, treatment, and outcomes. The secondary use of clinical information in this study was approved by the Ethics Committee of the Hyogo Prefectural Kobe Children’s Hospital (Ethics Review Number R6-69).
Neurodevelopmental disorders were diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [9] following the Kyoto Scale of Psychological Development (K-test) 2020 and Modified Checklist for Autism in Toddlers (M-CHAT). The K-test is one of the most widely used developmental tests in Japan to assess developmental age (DA) and developmental quotients (DQ) [10]. The K-test is an individualized, face-to-face assessment administered by experienced psychologists to individuals aged 0–80 years, and evaluates development in the following three domains: Postural–Motor (P-M; fine and gross motor functions); Cognitive–Adaptive (C-A; non-verbal reasoning or visuospatial perception assessed using materials such as blocks, miniature cars, and marbles); and Language–Social (L-S; interpersonal relationships, socialization, and verbal abilities). It usually takes approximately 20–40 min to administer [10]. In each of the three domains, a sum score is converted to a DA, and an overall DA is also obtained. The three domain DAs and the overall DA are divided by the child’s chronological age and multiplied by 100 to yield four DQ scores. These DQ scores have been considered to be equivalent to IQ [11].
Meanwhile, the M-CHAT is currently one of the most widely used ASD screening instruments in the United States and internationally, providing an accessible, low-cost option for universal toddler screening [12]. The M-CHAT is available in several languages and is a questionnaire for children aged 18–30 months. It consists of 23 items in total, including 16 items on social development, 4 items on perceptual responses and stereotyped behaviors characteristic of ASD, and 1 item on language comprehension; parents are asked to respond with yes/no [12]. The reliability and validity of the Japanese version of the M-CHAT have also been verified. For example, the father–mother inter-rater reliability is reported to be 0.933, the test–retest reliability is 0.990, and the criterion-related validity with CARS is reported to be 0.581 [13].
Parent-interview Autism Spectrum Disorder Rating Scale–Text Revision (PARS-TR) assessments were conducted by pediatricians, developmental-behavioral pediatricians, and pediatric clinical psychologists in the Pediatric Rehabilitation Center of our hospital. PARS-TR is a screening instrument used to assess ASD in Japan through interviews with the patients’ primary caregivers [14]. In this study, a pediatric neurologist scored the rating scale. The minimum eligible age for assessment by PARS-TR is 3 years. The scale consists of 57 items classified into six subscales: interpersonal relations, communication, obsession, stereotyped behaviors, difficulty in living, and hypersensitivity (34 items for preschoolers, 33 items for school-age children, and 33 items for adolescence and adulthood). The severity of each item is rated on a 3-point scale (0, 1, and 2). The higher the total score, the more likely it is that the assessed child has ASD [14]. The cutoff value for the PARS-TR for the diagnosis of pervasive developmental disorder is 9 points, with a sensitivity of 0.89, specificity of 0.94, and predictive value of 0.96 [15].
A child eating disorder diagnosis was classified based on the Great Ormond Street Criteria (GOSC) [16]. “Calcium Up Nar®” (FINE JAPAN CO., Ltd, Osaka, Japan) was the multiple-micronutrient powder used to supplement vitamin C. It is tasteless and odorless and is commercially available as a food product. Each gram contains 133 µg vitamin A, 9.2 µg vitamin D, 0.2 mg vitamin B1, 0.23 mg vitamin B6, 0.4 µg vitamin B12, 40 µg folic acid, and 16.7 mg vitamin C [17]. One gram per meal was either mixed with white rice before cooking, blended into food ingredients, or sprinkled over meals before serving.
Results
During the study period, 13 cases of scurvy were reported. Patient backgrounds are shown in Table 1. The median age [interquartile range] of the patients was 52 [42–65] months, with seven (54%) being male. The median body height SDS [interquartile range] was − 1.41 [-3.39–2.70], and the median BMI SDS [interquartile range] was − 1.19 [-3.45 to -0.40]. Twelve patients (92%) were diagnosed with neurodevelopmental disorders, seven patients (54%) with ASD, five patients (38%) with suspected ASD, and eleven patients (85%) with intellectual disorders. Two patients had a medical history of physical disease: one of hematologic malignancy and one of congenital heart disease. All patients were diagnosed with an eating disorder: ten exhibited selective eating, while three demonstrated restrictive eating. Among the patients with restrictive eating habits, one had ASD, one had suspected ASD, and one had a hematologic malignancy. These individuals consumed a variety of foods, including white rice, wheat products, potatoes, meat, and fish, but all consumed few vegetables or fruits in their diet. The median [interquartile range] estimated vitamin C intake, calculated based on dietary interviews conducted by dietitians, was 0 [0–5.25] mg/day.
Table 1.
Background data
| N=13 | |
|---|---|
| Age (month), median [IQR] | 52 [42, 65] |
| Male, n (%) | 7 (53.8) |
| Body height SDS, median [IQR] | -1.41 [-3.39, 2.70] |
| BMI SDS, median [IQR] | -1.19 [-3.45, -0.40] |
| Medical history | |
| Neurodevelopmental disorders, n (%) | 12 (92.3) |
| Autism spectrum disorder, n (%) | 7 (53.8) |
| Suspicion of autism spectrum disorder, n (%) | 5 (38.4) |
| Intellectual disorders, n (%) | 11 (84.6) |
| Hematologic malignancy, n (%) | 1 (7.7) |
| Congenital heart disease, n (%) | 1 (7.7) |
| Classification of eating disorders | |
| Selective eating, n (%) | 10 (76.9) |
| Restrictive eating, n (%) | 3 (23.1) |
| Duration of diagnosis (day), median [IQR] | 43 [19, 49] |
| Diagnosis at the previous doctor | |
| IgA vasculitis, n (%) | 3 (23.1) |
| Anemia, n (%) | 1 (7.7) |
| Arthritis, n (%) | 1 (7.7) |
| Fever of unknown origin, n (%) | 1 (7.7) |
| Osteomyelitis, n (%) | 1 (7.7) |
| Simple hip joint arthritis, n (%) | 1 (7.7) |
SDS, standard deviation score; IQR, interquartile range
The median duration from onset to diagnosis [interquartile range] was 43 [19–49] days, with seven patients (54%) requiring more than 30 days to be diagnosed with scurvy. At previous institutions, three patients had been diagnosed with IgA vasculitis, two with arthritis, and one each with anemia, osteomyelitis, and fever of unknown origin.
The clinical symptoms and laboratory findings at the time of scurvy diagnosis are shown in Table 2. Eleven (85%) patients exhibited gait disturbances. Nine patients (69%) had joint pain, six (46%) had fever, five (39%) had purpura or petechiae, and four (31%) had gum bleeding or swelling. The serum vitamin C level at diagnosis was < 5.0 µg/mL in all 13 cases, with 7 cases (54%) showing a level ≤ 0.2 µg/mL. Eleven patients (85%) had deficiencies in other nutrients, including iron, zinc, selenium, folic acid, carnitine, and vitamins A, B1, B2, B12, D, and K. The median hemoglobin level [interquartile range] was 10.2 [5.2–13.6] g/dL, the median platelet level [interquartile range] was 31.0 [25.1–38.8] × 104/µL, and the median D-dimer level [interquartile range] was 1.9 [0.5–11.0] µg/mL (Table 2). Radiography was performed in eight cases (62%), revealing abnormalities such as metaphyseal lucencies, cortical thinning, and coarse trabeculation in five cases. Magnetic resonance imaging (MRI) performed in six cases (46%) showed heterogeneous T2 hyperintensity in the bilateral lower extremities in all cases. Knee ultrasound performed in four cases (31%) identified joint hematomas or abnormal signals in the surrounding soft tissues in three cases.
Table 2.
Clinical symptoms and laboratory findings
| N=13 | |
|---|---|
| Symptoms | |
| Fever, n (%) | 6 ( 46.2) |
| Gait disturbance, n (%) | 11 (84.6) |
| Gum bleeding or swelling, n (%) | 4 (30.8) |
| Joint pain, n (%) | 9 (69.2) |
| Purpura or petechiae, n (%) | 5 (38.5) |
| Blood test | |
| C-reactive protein (mg/dL), median [IQR] | 0.43 [0.17, 0.99] |
| Hemoglobin (g/dL), median [IQR] | 10.2 [8.8, 11.7] |
| Mean cell volume (fL), median [IQR] | 74.1 [71.8, 78.9] |
| Platelets (×104/μL), median [IQR] | 31 [25.1, 38.8] |
| PT-INR, median [IQR] | 1.0 [0.94, 1.05] |
| APTT (s), median [IQR] | 25.95 [24.55, 29.47] |
| D-dimer (μg/mL), median [IQR] | 1.9 [1.10, 4.10] |
| Vitamin C (μg/mL)†, median [IQR] | 0.2 [0.20, 2.60] |
| Imaging test | |
| X-ray, n (%) | 8 (26) |
| Metaphyseal lucencies, cortical thinning, and coarse trabeculation, n | 5 |
| Ultrasound examination, n (%) | 4 (31) |
| Joint hematomas or abnormal signals in the surrounding soft tissues, n | 3 |
| MRI, n (%) | 6 (46) |
| T2 hyperintensity in the bilateral lower extremities, n | 4 |
| CT, n (%) | 1 (8) |
| Other nutritional deficiencies | |
| Vitamin B1, n (%) | 4 (30.8) |
| Vitamin B2, n (%) | 3 (23.1) |
| Vitamin B12, n (%) | 3 (23.1) |
| Vitamin D, n (%) | 5 (38.5) |
| Vitamin K, n (%) | 1 (7.7) |
| Vitamin A, n (%) | 7 (53.8) |
| Folic acid, n (%) | 2 (15.4) |
| Carnitine, n (%) | 3 (25.0) |
| Iron, n (%) | 6 (46.2) |
| Zinc, n (%) | 4 (30.8) |
| Selenium, n (%) | 2 (15.4) |
PT-INR, prothrombin time/international normalized ratio; APTT, activated partial thromboplastin time; IQR, interquartile range
†<0.2 μg/mL calculated as 0.20 μg/mL
The treatments are listed in Table 3. In all cases, dietitians provided caregivers with nutritional assessment, guidance, and education on appropriate diets at least once, and the median [interquartile range] number of nutritional counseling sessions received within one year after diagnosis was 2 [2–4]. However, there were no cases in which patients were able to consume enough vitamin C from diet al.one within a short period. Six patients (46%) initially received intravenous vitamin C, and all patients who received intravenous administration were subsequently transitioned to prescription vitamin formulation or multiple-micronutrient supplement powders that included vitamin C. Seven patients (54%) were treated with the prescription vitamin formulation, but four patients who took the medication at the start of treatment soon began to refuse to take it, so they were switched to multiple-micronutrient supplement powder. Among the nine patients for whom oral administration of a prescription vitamin formulation was attempted, five had difficulty taking it because of selective eating. In these cases, attempts to administer prescription vitamin formulations not only led to the refusal of the prescription vitamin formulation but also resulted in the refusal of regular meals. Ultimately, multiple-micronutrient supplement powders that were tasteless, odorless, and sold as food were introduced to 11 patients. By mixing them into regular meals or beverages, oral intake was achieved in all patients. Four patients were able to take prescribed vitamins orally but were switched to commercial multiple-micronutrient supplement powders, which, when taken orally, eliminate the need for continuous hospital visits. The median [interquartile range] time to symptom improvement after treatment initiation was 10 [5–17.0] days, and none of the patients required tube feeding after discharge. The median [interquartile range] duration from diagnosis to the first confirmation of a normal serum vitamin C level (> 5.5 µg/mL) was 38 [14–64] days, and the median [interquartile range] serum vitamin C level at that time was 14.8 [11.2–16.1] µg/mL. The median [interquartile range] of the serum vitamin C levels, evaluated at the most remote outpatient visit between 1 and 6 months after the initiation of treatment for each patient, was 12.5 [11.7–18.0] µg/mL.
Table 3.
Treatment
| N=13 | |
|---|---|
| Acute phase | |
| Intravenous vitamin C administration, n (%) | 6 (46.2) |
| Oral administration of a prescription vitamin formulation, n (%) | 7 (53.8) |
| Patients who were unable to take the prescription vitamin formulation orally, n | 4 |
| Chronic phase | |
| Education on appropriate diet by dietitians, n (%) | 13 (100) |
| Patients who were unable to take the appropriate diet orally, n | 13 |
| Oral administration of a prescription vitamin formulation, n (%) | 9 (69.2) |
| Patients who were unable to take the prescription vitamin formulation orally, n | 5 |
| Oral administration of multiple micronutrient supplement powders, n (%) | 11 (84.6) |
| Patients who were unable to take the multiple micronutrient powders orally, n | 0 |
| Tube feeding, n (%) | 0 (0) |
Discussion
This retrospective study of 13 children showed that their scurvy was triggered by vitamin C deficiency due to an eating disorder and that they had comorbid conditions, such as neurodevelopmental disorders, including ASD and intellectual disabilities, and physical diseases, such as congenital heart disease and hematologic disorders. Although scurvy is treatable with vitamin C supplementation, treatment is not always straightforward because patients with developmental disorders often face challenges with dietary modifications and oral administration of supplements.
In children, comorbid conditions such as neurodevelopmental disorders, including ASD, developmental delays, and hematologic diseases, are commonly reported to be associated with scurvy [2]. Fifty to ninety% of patients with ASD exhibit selective eating behaviors, which tend to be more severe in children under 3 years of age [18–20]. In our series, nearly all patients showed developmental disorders; in particular, ASD was comorbid in 90%.
In addition, all patients exhibited significant eating disorders, and selective eating was more frequent than restrictive eating, as diagnosed according to the subtype classification of eating disorders. In our patients, vitamin C intake prior to the onset of scurvy was extremely low. There were no cases in which intestinal malabsorption was suspected, nor were any cases suggestive of child abuse. Serum vitamin C levels increased following the initiation of treatment. These findings suggest that eating disorders associated with neurodevelopmental disorders may have contributed to the onset of scurvy. The age at the onset of scurvy in this study was similar to the peak age for selective eating in children with ASD, suggesting that developmental disorders and associated selective eating are risk factors for pediatric scurvy.
This study also highlights that scurvy is often initially misdiagnosed, which leads to delays in treatment. Frequent symptoms of scurvy include lower-extremity pain (88%), gait disturbance (73%), petechiae (39%), and fever (17%) [2]. Symptoms of scurvy can resemble those of IgA vasculitis, transient synovitis, and osteomyelitis, making a diagnosis based solely on physical examinations difficult. Although a low serum vitamin C level is definitive for the diagnosis, because of dietary fluctuations, a normal serum vitamin C level does not rule out scurvy [21]. No specific blood test findings other than a low serum vitamin C level are indicative of scurvy. In this patient series, other than a decreased serum vitamin C level, no specific abnormalities were observed in blood tests. Scurvy may reveal high T2 signal intensity and periosteal reactions in multiple bones on imaging studies such as MRI [22], while X-rays may reveal findings such as metaphyseal calcification (Frankel line), lucent zones (Trümmerfeld zone), and periosteal calcification [23]. In some of the patients in our series, despite the presence of MRI findings characteristic of scurvy, the high T2 signal changes in the bone required differentiation from osteomyelitis and tumors. Diagnosing scurvy based solely on physical examinations and tests is challenging; thus, a thorough medical history, including symptoms, developmental history, and dietary history, is essential. A dietary history suggestive of vitamin C deficiency is the most useful tool for diagnosing scurvy. Vitamin C is abundant in fruits and vegetables but not in rice, wheat, meat, or dairy products. When evaluating children under selective feeding, it is important to carefully consider nutrients that may be deficient based on their dietary habits.
The treatment for scurvy is vitamin C administration, and symptoms typically improve within approximately one week, although improvements in the bones and skin may take several weeks [24]. A rapid response to vitamin C therapy is typical with scurvy and supports its diagnosis. As demonstrated in our study, treating scurvy resulting from selective eating associated with developmental disorders can be challenging. Intravenous nutrition or tube feeding may be required because of difficulties with oral administration, necessitating innovative treatment approaches. Children with developmental disorders exhibit low medication adherence, which is attributed to difficulties in cognitive function, behavior/emotions, and communication [25]. Children with developmental disorders are also prone to micronutrient deficiencies, highlighting the importance of vitamin and mineral supplementation [8]; however, they may experience difficulties in the introduction of complementary foods because of a lack of social skills, difficulty in adapting to changes in routine, and hypersensitivity to the sensory aspects of food [6]. In this study, administering a tasteless, odorless, multiple-micronutrient supplement powder to children who refused to take vitamin tablets enabled oral therapy for scurvy, and no patient required tube feeding. The nutritional supplements used in our study contained a balanced mix of various vitamins and minerals, allowing for treatment without increasing meal-related stress by adding them to foods regularly consumed by children. In our study, multiple patients exhibited nutrient deficiencies. In children with selective eating, various nutrients may be lacking, and supplementation with a single nutrient may be insufficient. The introduction of fortified foods that provide a well-balanced combination of nutrients is beneficial.
This study has some limitations. As a small observational study conducted at a single institution, the generalizability of the findings is limited. Additionally, owing to its retrospective nature, sufficient information regarding the diagnosis of scurvy and underlying conditions, as well as the selection of treatment strategies, may not have been collected. Further research is needed to clarify the epidemiology of scurvy and to establish appropriate treatment strategies. The data presented in this study do not demonstrate a causal relationship between eating disorders associated with neurodevelopmental disorders and the development of scurvy, but ultimately, since there was no recurrence in all cases after oral vitamin C intake was started, it was determined that the cause was insufficient oral intake due to eating disorders.
Conclusions
In this study, all of the patients had pediatric scurvy caused by feeding disorders accompanied by underlying neurodevelopmental disorders, physical diseases, or combinations thereof. Because the symptoms and clinical course of scurvy vary and it might be misdiagnosed, careful attention to dietary history is necessary. Moreover, when treating children with selective eating habits, oral medications are often difficult to administer. In terms of treatment, all patients presenting with ASD in this study had very limited oral food, but none required tube feeding, indicating that the use of tasteless, odorless, micronutrient supplement powder mixed into foods might be beneficial to these patients.
Acknowledgements
We thank the patients and their families for their participation in this study. We would also like to thank Editage (www.editage.jp) for the English language editing.
Abbreviations
- ASD
Autism spectrum disorder
- BMI
Body mass index
- SDS
Standard deviation score
Author contributions
TS, TK, and MS conceived of the study and developed the methodology. TS conducted the investigation and wrote the original draft. TK, MS, OS, MM, SA, and NY reviewed and edited the manuscript. NY supervised the study.
Funding
This work was partly supported by JSPS KAKENHI Grant Number JP 22K15941.
Data availability
Anonymized data presented in this manuscript are available for review upon reasonable request.
Declarations
Ethics approval and consent to participate
The secondary use of clinical information in this study was approved by the Ethics Committee of the Hyogo Prefectural Kobe Children’s Hospital (Ethics Review Number R6-69).
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Tomoki Saito, Email: t.saito.rq@gmail.com.
Kazumi Tomioka, Email: tomioka@med.kobe-u.ac.jp.
References
- 1.Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med. 1986;314:892–902. [DOI] [PubMed] [Google Scholar]
- 2.Trapani S, Rubino C, Indolfi G, Lionetti P. A narrative review on pediatric scurvy: the last Twenty years. Nutrients. 2022;14:684. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mimasaka S, Funayama M, Adachi N, Nata M, Morita M. A fatal case of infantile scurvy. Int J Legal Med. 2000;114:122–4. [DOI] [PubMed] [Google Scholar]
- 4.Duvall MG, Pikman Y, Kantor DB, Ariagno K, Summers L, Sectish TC, et al. Pulmonary hypertension associated with scurvy and vitamin deficiencies in an autistic child. Pediatrics. 2013;132:e1699–703. [DOI] [PubMed] [Google Scholar]
- 5.Kumar V, Choudhury P. Scurvy-a forgotten disease with an unusual presentation. Trop Doct. 2009;39:190–2. [DOI] [PubMed] [Google Scholar]
- 6.Wang T, Feng J, Xue Y, Shan L, Jia F, Yue X. Feeding problems, age of introduction of complementary food and autism symptom in children with autism spectrum disorder. Front Pediatr. 2022;10:860947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Tomioka K, Nishiyama M, Tokumoto S, Yamaguchi H, Nozu K, Nagase H. Behavioral therapy for children with avoidant/restrictive food intake disorder dependent on tube or oral enteral nutrient formula: a feasibility study. Kobe J Med Sci. 2022;67:E155–60. [PMC free article] [PubMed] [Google Scholar]
- 8.Doherty M, Foley KR, Schloss J. Complementary and alternative medicine for autism - a systematic review. J Autism Dev Disord. 2024. 10.1007/s10803-024-06449-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.American Psychiatric Association. Diagnostic and statistical manual of mental disorders. DSM-5). 5th ed. Washington, D.C.: American Psychiatric Publication; 2013. [Google Scholar]
- 10.Society for the Kyoto Scale of Psychological Development Test. Shinpan K Shiki Hattatsu Kensahou 2001 Nenban [The Kyoto scale of psychological development test 2001]. Kyoto: Nakanishiya Shuppan; 2008. (in Japanese). [Google Scholar]
- 11.Kurita H, Osada H, Shimizu K, Tachimori H. Validity of DQ as an estimate of IQ in children with autistic disorder. Psychiatry Clin Neurosci. 2003;57(2):231–3. [DOI] [PubMed] [Google Scholar]
- 12.Robins DL, Fein D, Barton ML, Green JA. The modified checklist for autism in toddlers: an initial study investigating the early detection of autism and pervasive developmental disorders. J Autism Dev Disord. 2001;31(2):131–44. [DOI] [PubMed] [Google Scholar]
- 13.Kamio Y, Inada N, Koyama T, Inokuchi E, Tsuchiya K, Kuroda M. Effectiveness of using the modified checklist for autism in toddlers in two-stage screening of autism spectrum disorder at the 18-month health check-up in Japan. J Autism Dev Disord. 2014;44(1):194–203. [DOI] [PubMed] [Google Scholar]
- 14.Kitaoka T, Morimoto M, Hashimoto T, Tsuda Y, Nakatsu T, Kyotani S. Evaluation of the efficacy of drug treatment based on measurement of the oxidative stress, using reactive oxygen metabolites and biological antioxidant potential, in children with autism spectrum disorder and attention deficit hyperactivity disorder. J Pharm Health Care Sci. 2020;6:8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Masatsugu Tsujii R, Yukihiro J, Adachi H, Ichikawa M, Inoue TU. Reliability and validity of short version of pervasive developmental disorders (PDD)-Autism society Japan rating scale (PARS): A behavior checklist for people with PDD. Japanese J Clin Psychiatry.2006;35(8):1119–26.
- 16.Lask B, Bryant-Waugh R. Eating disorders in childhood and adolescence. 4th ed. New York: Routledge; 2013. [Google Scholar]
- 17.FINE, JAPAN CO. https://medifine.jp/product/2308, Accessed 13 October 2025.
- 18.Tanner K, Case-Smith J, Nahikian-Nelms M, Ratliff-Schaub K, Spees C, Darragh AR. Behavioral and physiological factors associated with selective eating in children with autism spectrum disorder. Am J Occup Ther. 2015;69:p69061800301–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Williams PG, Dalrymple N, Neal J. Eating habits of children with autism. Pediatr Nurs. 2000;26:259–64. [PubMed] [Google Scholar]
- 20.Viviers M, Jongh M, Dickonson L, Malan R, Pike T. Parent-reported feeding and swallowing difficulties of children with autism spectrum disorders (aged 3 to 5 years) compared to typically developing peers: a South African study. Afr Health Sci. 2020;20:524–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Agarwal A, Shaharyar A, Kumar A, Bhat MS, Mishra M. Scurvy in pediatric age group - a disease often forgotten? J Clin Orthop Trauma. 2015;6:101–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Gulko E, Collins LK, Murphy RC, Thornhill BA, Taragin BH. MRI findings in pediatric patients with scurvy. Skeletal Radiol. 2015;44:291–7. [DOI] [PubMed] [Google Scholar]
- 23.Tamura Y, Welch DC, Zic JA, Cooper WO, Stein SM, Hummell DS. Scurvy presenting as painful gait with bruising in a young Boy. Arch Pediatr Adolesc Med. 2000;154:732–5. [DOI] [PubMed] [Google Scholar]
- 24.Ioris MAD, Geremia C, Diamanti A, Lombardi MH, Papa RE, Campana A. Risks of inadequate nutrition in disabled children: four cases of scurvy. Arch Dis Child. 2016;101:871. [DOI] [PubMed] [Google Scholar]
- 25.Logan SL, Carpenter L, Leslie RS, Hunt KS, Garrett-Mayer E, Charles J, et al. Rates and predictors of adherence to psychotropic medications in children with autism spectrum disorders. J Autism Dev Disord. 2014;44:2931–48. [DOI] [PubMed] [Google Scholar]
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Data Availability Statement
Anonymized data presented in this manuscript are available for review upon reasonable request.