Long-term complications in classic galactosemia are not progressive.

Classic galactosemia (CG) is a potentially lethal genetic disorder that results from profound deficiency of galactose-1-P uridylyltransferase. Despite early detection and life-long dietary restriction of galactose, which is the current standard of care, many patients with CG grow to experience a range of long-term developmental complications that can include difficulties with speech/voice/language, cognitive, motor, and psychosocial outcomes, among other problems. That these complications are common in CG is well-documented, but whether they are also progressive has been a point of controversy for decades. Here, we addressed the question of whether long-term outcomes in CG are progressive by analyzing a robust data set in each of 4 ways. First, we compared cross-sectional Vineland-3 Adaptive Behavior Scales scores for 101 cases and 65 unaffected sibling controls and found no evidence of consistently declining scores with age. Second, we analyzed longitudinal Vineland-3 subdomain scores for 45 cases and 34 controls to see if individual participants demonstrated developmental gains (positive slope) or losses (negative slope) over time. The changes in most growth scale value (GSV) scores, which are not normed, were positive for both cases and controls <10y, and either positive or near zero for participants ≥10y. In contrast, the slopes of most v-Scale scores, which are normed, were negative for many cases <10y, indicating that these children, while gaining milestones, were gaining them at a slower pace than their counterparts in the reference population. Third, we analyzed medical records from 76 cases, assigning ordinal scores for complications and gathering the quantitative results of relevant formal assessments where available. Both cross-sectional and longitudinal analyses of both ordinal and formal assessment scores confirmed that outcomes were mostly stable, albeit with some ups and downs in isolated cases. Finally, we analyzed data collected via custom family-response surveys from 124 cases and 67 controls regarding each participant's perceived symptom severity over time. Among cases, the percentages of respondents reporting worsening symptoms over time for speech, cognitive, motor, and psychosocial outcomes were 0.8%, 6.6%, 5.2%, and 9.8%, respectively. Among controls, the corresponding percentages were 0.0%, 1.5%, 1.5%, and 6.5%, respectively. These results provide compelling evidence that long-term developmental complications are not progressive for a majority of patients with CG.

Racial and ethnic diversity of classic and clinical variant galactosemia in the United States.

Classic and clinical variant galactosemia (CG/CVG) are allelic, autosomal recessive disorders that result from deficiency of galactose-1-P uridylyltransferase (GALT). CG/CVG has been reported globally among patients of diverse ancestries, but most large studies of outcomes have included, almost exclusively, patients categorized as White or Caucasian. As a first step to explore whether the cohorts studied are representative of the CG/CVG population at large, we sought to define the racial and ethnic makeup of CG/CVG newborns in a diverse population with essentially universal newborn screening (NBS) for galactosemia: the United States (US). First, we estimated the predicted racial and ethnic distribution of CG/CVG by combining the reported demographics of US newborns from 2016 to 2018 with predicted homozygosity or compound heterozygosity of pathogenic, or likely pathogenic, GALT alleles from the relevant ancestral groups. Incorporating some simplifying assumptions, we predicted that of US newborns diagnosed with CG/CVG, 65% should be White (non-Hispanic), 23% should be Black (non-Hispanic), 10% should be Hispanic, and 2% should be Asian (non-Hispanic). Next, we calculated the observed racial and ethnic distribution of US newborns diagnosed with CG/CVG using available de-identified data from state NBS programs from 2016 to 2018. Of the 235 newborns in this cohort, 41 were categorized as other or unknown. Of the remaining 194, 66% were White (non-Hispanic or ethnicity unknown), 16% were Black (non-Hispanic or ethnicity unknown),15% were Hispanic, and 2% were Asian (non-Hispanic or ethnicity unknown). This observed distribution was statistically indistinguishable from the predicted distribution. To the limits of our study, these data confirm the racial and ethnic diversity of newborns with CG/CVG in the US, demonstrate an approach for estimating CG/CVG racial and ethnic diversity in other populations, and raise the troubling possibility that current understanding of long-term outcomes in CG/CVG may be skewed by ascertainment bias of the cohorts studied.

Who decides? Consent for healthcare decisions of minors in the United States.

PURPOSE OF REVIEW: The purpose of this review is to examine when parents and legal guardians have the authority to make medical decisions on behalf of the minors in their care, when the decisions of healthcare professionals may supersede those of parents and guardians, and under what conditions minors can make healthcare decisions for themselves. RECENT FINDINGS: The coronavirus disease 2019 (COVID-19) pandemic has reignited discussion of who should make healthcare decisions for minors. Though serious adverse reactions to COVID-19 vaccines are rare, hesitancy toward pediatric COVID-19 vaccination is prevalent among parents in the United States. This has contributed to large numbers of minors who are not up-to-date or not fully vaccinated against severe acute respiratory syndrome coronavirus 2 infection. Surveys reveal a majority of minors in the United States are willing to receive a COVID-19 vaccine. A number of scholars have recommended allowing adolescents the ability to consent to COVID-19 vaccination without parental approval. SUMMARY: Allowing adolescents with a minimum age of 15 to consent to vaccination without parental or guardian approval will more quickly enable adolescents to receive new vaccines as they become available, such as the COVID-19 bivalent vaccine.