Mitzie Grant

Severity of obstructive sleep apnea in children with sickle cell disease.

Objective To characterize polysomnographic (PSG) findings of children with sickle cell disease (SCD) suspected of having sleep disordered breathing (SDB). Methods Families of 100 consecutively referred children with SCD completed the Childrens Sleep Habit Questionnaire during a routine visit to identify concerns regarding sleep habits and sleep behavior. Of these, 48 children were identified as displaying behaviors suspicious of SDB. Nineteen agreed to an overnight PSG. The results from the PSGs of the SCD with obstructive sleep apnea syndrome (OSAS) group (SCD-OSAS; group 1) were compared with the results of 10 age, sex, and ethnicity-matched patients identified as OSAS with no medical comorbidities (uncomplicated OSAS; group 2). Results SDB was identified in 79% of the SCD group. As compared with the uncomplicated OSAS group, the SCD with OSAS group displayed nocturnal desaturation with lower nadir values, of longer duration, with a 4-fold increased risk for oxygen desaturation below 85%, higher percentage of total sleep time with end-tidal carbon dioxide (ET CO2) values >50 mm Hg, with a 3.7-fold increased risk for spending more than 25% of total sleep time with ET CO2 more than 50 mm Hg and higher peak ET CO2 with a 7-fold increase for peak ET CO2 above 53 mm Hg. Conclusions Children with SCD suspicious of SDB may have not only a higher incidence of OSAS, but also more severe nocturnal desaturation and hypercapnia as compared with children with uncomplicated OSAS.

Newborn screening 50 years later: access issues faced by adults with PKU

Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease.Genet Med 2013:15(8):591–599

Chronic sorrow and coping in families of children with epilepsy.

&NA; Epilepsy, a common problem in child neurology, affects the entire family. There is a potential for such psychosocial consequences as parental chronic sorrow and alterations in coping. In this study, 67 parents completed brief questionnaires about their sorrow and coping styles. Results demonstrated chronic sorrow as measured by the Adapted Burke Questionnaire (10.45±7.9). Interestingly, the total score was not significantly different between parents of children with refractory and nonrefractory epilepsy or parents of children with comorbid or without comorbid conditions. Selection of the individual item disbelief, however, was significantly increased in parents of children with nonrefractory epilepsy, and selection of the item anger was significantly increased in parents of children with comorbid conditions. Parental coping styles were similar to those reported in the normative data for the instrument used, the Coping Health Inventory for Parents (CHIP). The correlation between chronic sorrow and coping was significant between the grief component of sorrow and Coping Pattern II of the CHIP. Implications for practice include earlier identification of parental feelings of sorrow and coping styles, which may contribute to a positive outcome.

The role of intelligence in phenylketonuria: a review of research and management.

Phenylketonuria (PKU) results in profound intellectual disability in untreated individuals and more subtle cognitive deficits in individuals treated early and continuously. The assessment of intellectual functioning has been an important outcome variable and the focus of extensive research. Since the implementation of neonatal PKU screening programs in the 1960s, research on intellectual functioning in individuals with PKU has played a significant and positive role in guiding therapy and improving results. This is a literature review examining the relationship between intellectual outcome and treatment parameters including initiation of treatment, duration of treatment, and blood phenylalanine (Phe) levels from infancy through adulthood. While current PKU treatment practices have eliminated severe neurological and cognitive impairment, evidence suggests that intellectual functioning, although typically within the average range when PKU is treated early and continuously, may not be maximized under the current definition of well-controlled PKU, which is based on blood Phe levels. Future research assessing intellectual and neurocognitive outcome in PKU will enhance the development of new treatment strategies.

Neuropsychological Functioning in Preschool-age Children with Sickle Cell Disease: The Role of Illness-related and Psychosocial Factors

Cognitive and academic deficits have been identified in school-aged children with sickle cell disease (SCD). However, there have been very few identified studies that examine neuropsychological functioning in preschool-age children with SCD. It is important to understand effects of SCD from a developmental perspective and to consider the contribution of environmental factors in this at-risk population. Neuropsychological functioning of preschool-age children with SCD and no history of overt stroke (n = 26) was examined across several domains (language, immediate memory/brief attention, visuospatial/visuoconstructional, motor/visuomotor). The mean Full Scale IQ for the sample was 89.0. Performance on the Immediate Memory/ Brief Attention domain was significantly higher than the other domains, although the pattern of performance was relatively consistent, with mean standard scores ranging from 88.0 to 95.0. Disease severity was not significantly related to cognitive functioning in this group of young children with SCD. Socioeconomic status (SES) was significantly correlated with most domain scores and, based on regression analyses, accounted for 18% to 47% of the variance in functioning. Psychosocial factors, such as number of children living in the home and parental stress levels, were negatively associated with Motor/Visuomotor skills, and weekly hours in school/day care was positively associated with language-related skills. Results suggest that, at this young age, psychosocial risk factors appear to be appropriate targets for intervention, with the goal of improving long-term outcome in children with SCD. Further investigations should include comparison to a matched control group.

Sleep patterns in pediatric sickle cell disease

Research examining sleep in children with sickle cell disease (SCD) has focused on the increased occurrence of specific sleep disorders (i.e., sleep‐disordered breathing, hypoxemia, nocturnal enuresis), but no research exists describing general sleep behaviors of children with SCD. The purpose of the current study was to compare sleep patterns and sleep behaviors in children with SCD and healthy controls and examine the associations of demographic and disease factors with sleep in the SCD group.

Correlation between child and parental perceptions of health-related quality of life in epilepsy using the PedsQL.v4.0 measurement model

Health-related quality-of-life measures in childhood epilepsy are typically limited to a particular functional domain, specific age group, parent proxy-report, or child self-report. Generic health-related quality-of-life instruments in paediatric epilepsy comparing child self-reports with simultaneous parent proxy-reports have not been previously investigated. A previously validated generic questionnaire, the Pediatric Quality of Life version 4 (PedsQL.v4.0), was used to prospectively assess parental and child perceptions of health-related quality of life in 100 children with epilepsy. The correlation between child and parental health-related quality-of-life perceptions across all domains was excellent (p < 0.001) and both were significantly lower than those for healthy controls (p < 0.001). Parents’ perceptions of their children’s healthrelated quality of life were lower than those for other chronic illnesses (p < 0.001), especially for refractory epilepsy. The presence of neurological or psychiatric comorbidities also had an adverse impact on health-related quality of life. The PedsQL.v4.0 measures health-related quality of life from both the parent’s and child’s perspective. Ease of use makes this instrument attractive for routine clinical use.

A randomized, placebo-controlled, double-blind study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria

Symptoms of attention deficit-hyperactivity disorder (ADHD), particularly inattention, and impairments in executive functioning have been reported in early and continuously treated children, adolescents, and adults with phenylketonuria (PKU). In addition, higher blood phenylalanine (Phe) levels have been correlated with the presence of ADHD symptoms and executive functioning impairment. The placebo-controlled PKU ASCEND study evaluated the effects of sapropterin therapy on PKU-associated symptoms of ADHD and executive and global functioning in individuals who had a therapeutic blood Phe response to sapropterin therapy. The presence of ADHD inattentive symptoms and executive functioning deficits was confirmed in this large cohort of 206 children and adults with PKU, of whom 118 responded to sapropterin therapy. In the 38 individuals with sapropterin-responsive PKU and ADHD symptoms at baseline, sapropterin therapy resulted in a significant improvement in ADHD inattentive symptoms in the first 4 weeks of treatment, and improvements were maintained throughout the 26 weeks of treatment. Sapropterin was well-tolerated with a favorable safety profile. The improvements in ADHD inattentive symptoms and aspects of executive functioning in response to sapropterin therapy noted in a large cohort of individuals with PKU indicate that these symptoms are potentially reversible when blood Phe levels are reduced.

Prevalence, Incidence and Persistence of Psychiatric and Substance Use Disorders Among Mothers Living with HIV

Objective:To evaluate prevalence, incidence, remission, and persistence of psychiatric and substance use disorders among HIV-infected mothers and identify biopsychosocial correlates. Methods:HIV-infected mothers (n = 1223) of HIV-exposed uninfected children enrolled in a prospective cohort study; HIV-uninfected mothers (n = 128) served as a comparison group. Mothers provided sociodemographic and health information and completed the Client Diagnostic Questionnaire (CDQ). Prevalence of any psychiatric or substance use disorder at initial evaluation was compared between the 2 groups. Incident, remitting, and persisting disorders were identified for 689 mothers with HIV who completed follow-up CDQs. We used logistic regression to evaluate adjusted associations of biopsychosocial characteristics with presence, incidence, remission, and persistence of disorders. Results:Thirty-five percent of mothers screened positive for any psychiatric or substance use disorder at initial evaluation, with no difference by maternal HIV status (P = 1.00). Among HIV-infected mothers, presence of any disorder was associated with younger age [adjusted odds ratio (aOR): 1.39; 95% CI: 1.09 to 1.75], single parenthood (aOR: 1.35; 95% CI: 1.08 to 1.68), and functional limitations (aOR: 2.29; 95% CI: 1.81 to 2.90). Incident disorders were associated with functional limitations (aOR: 1.92; 95% CI: 1.10 to 3.30). Among HIV-infected mothers with a disorder at initial evaluation (n = 238), 61% had persistent disorders. Persistent disorders were associated with lower income (aOR: 2.44; 95% CI: 1.33 to 4.76) and functional limitations (aOR: 3.19; 95% CI: 1.87 to 5.48). Receipt of treatment for any disorder was limited: 4.5% at study entry, 7% at follow-up, 5.5% at both entry and follow-up. Conclusions:Psychiatric and substance use disorders remain significant comorbid conditions among HIV-infected mothers and require accessible evidence-informed treatment.

Neuropsychiatric comorbidities in adults with phenylketonuria: A retrospective cohort study

Adults with phenylketonuria (PKU) may experience neurologic and psychiatric disorders, including intellectual disability, anxiety, depression, and neurocognitive dysfunction. Identifying the prevalence and prevalence ratios of these conditions will inform clinical treatment. This nested, case-controlled study used International Classification of Diseases, Ninth Revision (ICD-9) codes from the MarketScan® insurance claims databases from 2006 to 2012 and healthcare claims data for US-based employer and government-sponsored health plans. Prevalence and prevalence ratio calculations of neuropsychiatric comorbidities for adults (≥20years old) with PKU were compared with two groups [diabetes mellitus (DM) and general population (GP)] matched by age, gender, geographic location, and insurance type. Age cohorts (i.e., 20-29, 30-39, 40-49, 50-59, 60-69, and 70+years, and a combined subset of 20-39) were used to stratify data. The PKU cohort experienced significantly higher rates of several comorbid neurologic, psychiatric and developmental conditions. Compared to GP, PKU was associated with significantly higher prevalence for numerous neuropsychiatric conditions, most notably for intellectual disability (PR=7.9, 95% CI: 6.4-9.9), autism spectrum disorder (PR=6.1, 95% CI: 3.6-10.4), Tourette/tic disorders (PR=5.4, 95% CI: 2.1-14.1), and eating disorders (4.0, 95% CI: 3.2-5.0). Rates of fatigue/malaise, epilepsy/convulsions, sleep disturbance, personality disorders, phobias, psychosis, and migraines among those with PKU exceeded rates for the GP but were comparable to those with DM, with significantly lower rates of concomitant disorders occurring in younger, compared to older, adults with PKU. Lifelong monitoring and treatment of co-occurring neuropsychiatric conditions are important for effective PKU management.