Comprehensive and long-term outcomes of enzyme replacement therapy followed by stem cell transplantation in children with Gaucher disease type 1 and 3.

BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder, characterized by hepatosplenomegaly, pancytopenia, bone diseases, with or without neurological symptoms. Plasma glucosylsphingosine (lyso-Gb1), a highly sensitive and specific biomarker for GD, has been used for diagnosis and monitoring the response to treatment. Enzyme replacement therapy (ERT) is an effective treatment for the non-neurologic symptoms of GD. Neuronopathic GD (type 2 and 3) accounts for 60%-70% of the Asian affected population. METHODS: We explored combination therapy of ERT followed by hematopoietic stem cell transplantation (HSCT) and its long-term outcomes in patients with GD type 3 (GD3). RESULTS: Four patients with GD3 and one with GD type 1 (GD1) underwent HSCT. The types of donor were one matched-related, one matched-unrelated, and three haploidentical. The age at disease onset was 6-18 months and the age at HSCT was 3.8-15 years in the patients with GD3. The latest age at follow-up was 8-22 years, with a post-HSCT duration of 3-14 years. All patients had successful HSCT. Chronic graft-versus-host disease occurred in one patient. The enzyme activities were normalized at 2 weeks post HSCT. Lyso-Gb1 concentrations became lower than the pathological value. All of the patients are still alive and physically independent. Most of them (4/5) returned to school. None of the patients with GD3 had seizures or additional neurological symptoms after HSCT, but showed varying degrees of cognitive impairment. CONCLUSIONS: ERT followed by HSCT could be considered as an alternative treatment for patients with GD3 who have a high risk of fatal neurological progression.

Effectiveness of neurofeedback versus medication for attention-deficit/hyperactivity disorder.

BACKGROUND: Neurofeedback (NF) is an operant conditioning procedure that trains participants to self-regulate brain activity. NF is a promising treatment for attention-deficit/hyperactivity disorder (ADHD), but there have been only a few randomized controlled trials comparing the effectiveness of NF with medication with various NF protocols. The aim of this study was therefore to evaluate the effectiveness of unipolar electrode NF using theta/beta protocol compared with methylphenidate (MPH) for ADHD. METHODS: Children with newly diagnosed ADHD were randomly organized into NF and MPH groups. The NF group received 30 sessions of NF. Children in the MPH group were prescribed MPH for 12 weeks. Vanderbilt ADHD rating scales were completed by parents and teachers to evaluate ADHD symptoms before and after treatment. Student's t-test and Cohen's d were used to compare symptoms between groups and evaluate the effect size (ES) of each treatment, respectively. RESULTS: Forty children participated in the study. No differences in ADHD baseline symptoms were found between groups. After treatment, teachers reported significantly lower ADHD symptoms in the MPH group (P = 0.01), but there were no differences between groups on parent report (P = 0.55). MPH had a large ES (Cohen's d, 1.30-1.69), while NF had a moderate ES (Cohen's d, 0.49-0.68) for treatment of ADHD symptoms. CONCLUSION: Neurofeedback is a promising alternative treatment for ADHD in children who do not respond to or experience significant adverse effects from ADHD medication.

Effect of Chronic Rhinitis Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: The purpose of this study is to examine the effect of chronic rhinitis treatment on attention-deficit/hyperactivity disorder (ADHD) symptoms in children with ADHD. METHODS: Children and adolescents with ADHD were screened for chronic rhinitis symptoms. Participants with positive chronic rhinitis screening underwent the skin prick test and received rhinitis treatment for 3 months. All participants were evaluated using the parent's and teacher's Vanderbilt ADHD rating scales, total nasal symptom score, and Quality of Life Questionnaire (OSA-18) for pediatric obstructive sleep apnea at pretreatment and posttreatment. RESULTS: Overall, 140 children and adolescents with ADHD were enrolled and screened for chronic rhinitis. Fifty-four children and adolescents with positive screening results underwent the skin prick test and received rhinitis treatment. After 3 months of treatment, inattentive, hyperactive/impulsive, and total ADHD symptom scores were significantly decreased as reported by parents ( p = 0.031 to <0.001) and teachers ( p = 0.001 to <0.001) compared with those before treatment. A subgroup analysis also showed improvement in ADHD symptoms as reported by parents and teachers in the allergic and nonallergic rhinitis groups. Pearson's correlation coefficient analyses showed positive correlations between improvement in the ADHD symptom scores reported by parents and improvement in the quality of life related to sleep problems from the OSA-18 questionnaire (r = 0.377-0.387). CONCLUSION: Treating chronic rhinitis can improve ADHD symptoms in children and adolescents with ADHD. Pediatricians should be aware of and treat chronic rhinitis to maximize ADHD symptom control.

Improvement of inattentive and hyperactive symptoms after real-life rhinitis treatment in school-aged children.

OBJECTIVES: Rhinitis treatment may improve attention-deficit/hyperactivity symptoms in children. The current study evaluated changes in inattentive and hyperactive symptoms after treatment in children with chronic rhinitis. METHODS: Children aged 5-18 years with chronic rhinitis were enrolled in a 3-month prospective study. The nasal provocation test for house dust mites (HDM) and evaluation of allergen sensitization, including the skin prick test and the Phadiatop test, were performed. The severity of rhinitis was assessed according to the ARIA guideline. The total nasal symptom score and the Vanderbilt ADHD Diagnostic Rating Scale (VADRS) score for assessing inattentive and hyperactive symptoms were recorded at baseline and at 1 and 3 months after rhinitis treatment. Children with rhinitis were classified into the following two groups: HDM-induced allergic rhinitis (AR group) and non-allergic rhinitis to HDM (NAR group) based on the NPT. RESULTS: Overall, 83 children completed the 3-month prospective study, and they had a mean age of 9.12 ± 2.89 years and 44.6% were boys. After rhinitis treatment, VADRS scores assessed by the parents and teachers were significantly decreased compared with those at baseline (p = 0.005). In subgroup analysis, 61 (73.49%) children had AR, and 22 (26.5%) children had NAR. No significant difference in the baseline VADRS score was found between the AR and NAR groups. After treatment, VADRS scores assessed by the parents and teachers were significantly decreased only in the AR group (p < 0.001). Forty-five (54.2%) children had moderate persistent rhinitis, 29 (34.9%) had mild persistent rhinitis, and 9 (10.8%) had mild intermittent symptoms. There were no differences in baseline VADRS scores assessed by the parents and teachers among children with mild intermittent, mild persistent, or moderate persistent symptoms. The total nasal symptom score and VADRS score were significantly decreased after treatment for all severities of rhinitis compared with those at baseline. A greater baseline VADRS score was associated with substantial improvement of inattentive and hyperactive symptoms after treatment. CONCLUSION: Early treatment for rhinitis may improve inattentive and hyperactive symptoms in school-aged children.

Effect of Iron Supplementation in Children with Attention-Deficit/Hyperactivity Disorder and Iron Deficiency: A Randomized Controlled Trial.

OBJECTIVES: To determine the effectiveness of combined iron supplementation and methylphenidate treatment on attention-deficit/hyperactivity disorder (ADHD) symptoms in children/adolescents with ADHD and iron deficiency compared with methylphenidate alone. METHODS: In total, 116 children/adolescents with ADHD were screened for iron deficiency. Participants who exhibited iron deficiency were randomized into 2 groups (ferrous supplementation vs placebo). Vanderbilt ADHD rating scales were completed by parents and teachers at prestudy and poststudy periods. Student's t tests were used to determine improvements of Vanderbilt scores between the groups. RESULTS: Among 116 children who participated in this study, 44.8% (52/116) met the criteria for iron deficiency. Of the total 52 participants with iron deficiency, 26 were randomized to the ferrous group and 26 to the placebo group. Most participants in each group had been prescribed short-acting methylphenidate twice daily in the morning and at noon. After a 12-week study period, total parents' Vanderbilt ADHD symptom scores showed a significant improvement between the groups (mean decrement = -3.96 ± 6.79 vs 0 ± 6.54, p = 0.037). However, teachers' Vanderbilt ADHD symptom scores showed no difference between the groups. CONCLUSION: Children with ADHD and iron deficiency being on methylphenidate and iron supplementation had shown improvement of ADHD symptoms that were reported by parents.

Update on environmental risk factors for attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurobehavioral disorder affecting 5% to 10% of children. Although considered to be a highly familial disorder, ADHD heritability estimates of 60% to 80% highlight the considerable role that environmental factors may still play in disorder susceptibility. Proposed ADHD environmental risk factors include prenatal substance exposures, heavy metal and chemical exposures, nutritional factors, and lifestyle/psychosocial factors. This paper reviews the literature published in 2010 investigating the association between environmental risk factors and ADHD or related symptomatology. Sources of risk factor exposure and the proposed mechanism by which each exposure is linked to ADHD-related neurobehavioral changes are also reported. Methodologic limitations of the current literature are discussed, and guidelines for future study are proposed. An improved understanding of the role that environmental factors play in ADHD etiology is critical to future ADHD prevention efforts.

Early developmental outcome in children born to mothers with obstructive sleep apnea.

Obstructive sleep apnea (OSA) during pregnancy leads to adverse maternal and perinatal outcomes. There have been limited studies evaluated the effect of intrauterine exposure to maternal OSA on childhood developmental outcomes. This study was aimed to evaluate the early development of children born to mothers with gestational OSA and the impact of continuous positive airway pressure (CPAP) treatment. METHODS: Children aged 6-36 months, born to high risk pregnant mothers who had overnight polysomnography performed, were invited to participate. The Ages and Stages Questionnaires, third edition (ASQ-3), age-specific parent-completed questionnaires determining five developmental domains (communication, gross motor, fine motor, problem-solving, and personal-social) were used for developmental screening. Children who had a score of at least one domain less than -1 SD of age cut-off were determined as having a risk of developmental delay (RDD). RESULTS: There were 159 children (47% male, mean age 18 months) enrolled. The maternal PSG showed non-OSA, mild OSA, and moderate OSA in 14%, 46%, and 40%, respectively. Forty-two children (26%) had RDD, and the most affected domains were fine motor and problem-solving. Maternal moderate OSA was significantly associated with RDD (adjusted OR 5.39, 95%CI 1.11-26.12, P 0.037). Subgroup analysis showed that maternal moderate OSA with no CPAP treatment was significantly associated with RDD (OR 6.43, 95%CI 1.34-30.89, P = 0.020) CONCLUSION: Gestational moderate OSA in high-risk pregnancy mothers likely had a negative effect on early childhood developmental outcomes, particularly the mothers who did not have appropriate CPAP treatment.

Perspectives of adults with Klinefelter syndrome, unaffected adolescent males, and parents of affected children toward diagnosis disclosure: a Thai experience.

Little is known about disclosure of diagnosis to males with Klinefelter syndrome (KS) diagnosed before birth or during childhood, especially in Asian context. Insufficient preparation for disclosure communication could lead to the child's depression, anxiety, or disrupted self-esteem. This is an interventional and qualitative interview study with a brief self-reported survey. The study consists of three phases. In phase I, adults with KS were asked about their experiences and viewpoints toward KS disclosure and diagnosis through individual interviews. In phase II, unaffected adolescent males were given information about KS and then asked to give hypothetical answers to a questionnaire followed by a group interview, as if they had KS. In phase III, parents of children with KS were asked to complete a questionnaire followed by a group interview which included a discussion about their disclosure plans and their concerns. The parents were provided information obtained from adults with KS and unaffected adolescent males, and were then interviewed again as a group. We found that the most hurtful issues were discovering their infertility from KS and late disclosure. From the perspective of unaffected adolescent males, early disclosure in early or mid-teens in a neutral, supportive, and relaxed manner, along with information on benefits of hormonal treatment, the assurance of biological sex as "male," and avoidance of some sensitive words are strongly recommended, as a way to promote self-confidence and positive coping with the diagnosis. After intervention, the parents reported more confidence and less anxiety about disclosing the diagnosis to their children, and indicated that they would disclose KS at an earlier age. For unaffected adolescent males, though it is a hypothetical scenario and their reaction may differ from affected adolescents, unaffected adolescent males' viewpoints on how they might react are more or less representative of cultural changes for the new generation, especially in the Asian context. In addition, their viewpoints influenced parents' decision and genetic counseling plans for the diagnosis disclosure of KS to their children. We propose a preliminary guideline for KS diagnosis disclosure.

Correction to: Perspectives of adults with Klinefelter syndrome, unaffected adolescent males, and parents of affected children toward diagnosis disclosure: a Thai experience.

The article "Perspectives of adults with Klinefelter syndrome, unaffected adolescent males, and parents of affected children toward diagnosis disclosure: a Thai experience", written by Sukrit Suwannachat, Duangrurdee Wattanasirichaigoon, Jiraporn Arunakul, Vilawan Chirdkiatgumchai and Thipwimol Tim-Aroon, was originally published electronically on the publisher's internet portal (currently SpringerLink) on September 2019 without open access.

Autism spectrum disorders and their treatment with psychotropic medications in a nationally representative outpatient sample: 1994-2009.

PURPOSE: No prior studies have assessed change in health care provider-coded rates of Autism spectrum disorder (ASD) diagnoses over time, and few have investigated sociodemographic factors associated with having an ASD diagnosis, having behavioral conditions comorbid with ASD, or using psychotropic medications for this group. METHODS: We used data from the 1994-2009 National (Hospital) Ambulatory Medical Care Surveys for children aged 2-18 years (n = 158,488). RESULTS: Rates of visits with coded-ASD per 100 outpatient medical visits increased from 0.04% to 0.82% from 1994 to 2009. Factors associated with an ASD diagnosis included male gender, lack of private insurance, white race, and later study period. The most frequent comorbid behavioral diagnoses were ADHD, anxiety, disruptive behavior, and mood disorders. Older age was linked to an increased likelihood of having a comorbid behavioral diagnosis and using psychotropic medications. Geographic region was also associated with having a comorbid behavioral diagnosis, and psychotropic use was linked to have a behavioral comorbidity. Comorbidities with the highest rates of psychotropic use were ADHD, mood, and anxiety disorders. CONCLUSIONS: Pediatric outpatient visits with an ASD diagnosis have increased dramatically from 1994 to 2009. Further study is needed to determine the reasons for the observed sociodemographic disparities in ASD diagnosis.

National trends in psychotropic medication use in young children: 1994-2009.

OBJECTIVE: To examine recent national trends in psychotropic use for very young children at US outpatient medical visits. METHODS: Data for 2- to 5-year-old children (N = 43 598) from the 1994-2009 National Ambulatory and National Hospital Ambulatory Medical Care Surveys were used to estimate the weighted percentage of visits with psychotropic prescriptions. Multivariable logistic regression was used to identify factors associated with psychotropic use. Time effects were examined in 4-year blocks (1994-1997, 1998-2001, 2002-2005, and 2006-2009). RESULTS: Psychotropic prescription rates were 0.98% from 1994-1997, 0.83% from 1998-2001, 1.45% from 2002-2005, and 1.00% from 2006-2009. The likelihood of preschool psychotropic use was highest in 2002-2005 (1994-1997 adjusted odds ratio [AOR] versus 2002-2005: 0.67; 1998-2001 AOR versus 2002-2005: 0.63; 2006-2009 AOR versus 2002-2005: 0.64), then diminished such that the 2006-2009 probability of use did not differ from 1994-1997 or from 1998-2001. Boys (AOR versus girls: 1.64), white children (AOR versus other race: 1.42), older children (AOR for 4 to 5 vs 2 to 3 year olds: 3.87), and those lacking private insurance (AOR versus privately insured: 2.38) were more likely than children from other groups to receive psychotropic prescriptions. CONCLUSIONS: Psychotropic prescription was notable for peak usage in 2002-2005 and sociodemographic disparities in use. Further study is needed to discern why psychotropic use in very young children stabilized in 2006-2009, as well as reasons for increased use in boys, white children, and those lacking private health insurance.