Knowledge and attitudes about newborn screening for Fabry disease

Newborn screening is a public health program that identifies newborns who are at risk of having a life-threatening condition that will affect their health in infancy or childhood. Fabry disease is an X-linked lysosomal storage disorder with a variable age of onset from childhood through adulthood that was recently added to a few states’ newborn screening panels. Research on patient attitudes towards newborn screening for Fabry disease has been limited and this qualitative study aimed to gain a more complete understanding of the reasoning of adults with Fabry disease regarding the appropriateness of newborn screening for Fabry disease, their knowledge of newborn screening, and their experiences with Fabry disease. Participants were recruited from Children’s Hospital of Pittsburgh of UPMC’s Lysosomal Storage Disorders Clinic and six adults who have Fabry disease were interviewed. These interviews were transcribed and thematic analysis revealed six themes: influences of clinical spectrum and severity of Fabry disease, support systems, family dynamics, impact of timing of diagnosis and treatment availability on attitudes towards newborn screening, knowledge and attitudes towards newborn screening for Fabry disease, and impact of earlier diagnosis. Based on their personal experiences with Fabry disease, all participants were in favor of newborn screening for Fabry disease. Participants’ experiences with Fabry disease also reflected aspects of their family dynamics. The results of this qualitative study can inform genetic counseling practice for Fabry disease and future studies on NBS for Fabry disease. The opinions of stakeholders, including patients affected by the condition, are of public health significance and the results of this study can inform public health decisions as state legislators and state newborn screening programs consider whether to include Fabry disease on their state’s newborn screening panel

Prolactin rs1341239 T allele may have protective role against the brick tea type skeletal fluorosis

<div><p>Objective</p><p>Prolactin (PRL) has been reported to be associated with increased bone turnover, and increased bone turnover is also a feature of skeletal fluorosis (SF). Autocrine/paracrine production of PRL is regulated by the extrapituitary promoter and a polymorphism in the extrapituitary PRL promoter at -1149 (rs1341239) is associated with disturbances of bone metabolism in other diseases. Here, we have investigated the possibility that the rs1341239 polymorphism is associated with SF, which results from the consumption of brick tea.</p><p>Design</p><p>We conducted a cross-sectional study in Sinkiang, Qinghai, Inner Mongolia in China. Demography survey questionnaires were completed and physical examination and X-ray diagnoses were used to diagnose SF. Brick tea water fluoride intake (IF) and urinary fluoride (UF) were tested by an F-ion selective electrode method. A Sequenom MassARRAY system was used to determine PRL gene polymorphisms.</p><p>Results</p><p>Subjects who were younger than 45 years of age and carried the T allele had a significantly decreased risk of SF [OR = 0.279 (95%CI, 0.094–0.824)] compared to those carrying the homozygous G allele. This phenomenon was only observed in Kazakh subjects [OR = 0.127 (95%CI, 0.025–0.646)]. Kazakh females who carried T alleles has a decreased risk of SF [OR = 0.410 (95%CI, 0.199–0.847)]. For Kazakh subjects which IF is less than 3.5 mg/d, a decreased risk of SF was observed among the participants who carried T alleles [OR = 0.118 (95%CI, 0.029–0.472)]. Overall, subjects with 1.6–3.2 mg/L UF and carried T alleles had a significantly decreased risk of SF [OR = 0.476 (95%CI, 0.237–0.955)] compared to homozygous G allele carriers. This phenomenon was only observed in Kazakh subjects [OR = 0.324 (95%CI, 0.114–0.923)].</p><p>Conclusions</p><p>Our results suggested that the PRL rs1341239 T allele decreases the risk of brick tea SF.</p></div

Occurrence of genotype and allele frequencies of the PRL rs1341239 polymorphism in three ethnical subjects.

<p>Occurrence of genotype and allele frequencies of the PRL rs1341239 polymorphism in three ethnical subjects.</p

Representative images of brick-tea type skeletal fluorosis by X-ray examination.

<p>Normal (a) and (b): Normal forearm and shin. Mild (c) and (d): The interosseous membrane in the forearm or lower leg bone was mildly ossified with rough edges (arrows). Moderate (e) and (f): The radial crest and the border were enlarged; the interosseous membrane in the forearm or shin was ossified with serration or wave edge (arrows). Severe (g) and (h): The radial crest was enlarged and the border was obviously enlarged so that ulna and elbow joints presented severe degenerative changes; the interosseous membrane in the forearm or shin was obviously ossified with large shape (arrows).</p

General characteristics of study populations.

<p>General characteristics of study populations.</p

Associations between skeletal fluorosis and the PRL rs1341239 genotype (overall or stratified by ethnicity).

<p>Associations between skeletal fluorosis and the PRL rs1341239 genotype (overall or stratified by ethnicity).</p