Proposal of an Algorithm to Early Detect Attenuated Type I Mucopolysaccharidosis (MPS Ia) among Children with Growth Abnormalities

Background and Objectives: Diagnostic delay is common in attenuated Mucopolysaccharidosis Type I (MPS Ia) due to the rarity of the disease and the variability of clinical presentation. Short stature and impaired growth velocity are frequent findings in MPS Ia, but they rarely raise suspicion as paediatric endocrinologists are generally poorly trained to detect earlier and milder clinical signs of this condition. Materials and Methods: Following a consensus-based methodology, a multidisciplinary panel including paediatric endocrinologists, paediatricians with expertise in metabolic disorders, radiologists, and rheumatologists shared their experience on a possible clinical approach to the diagnosis of MPS Ia in children with short stature or stunted growth. Results: The result was the formation of an algorithm that illustrates how to raise the suspicion of MPS Ia in a patient older than 5 years with short stature and suggestive clinical signs. Conclusion: The proposed algorithm may represent a useful tool to improve the awareness of paediatric endocrinologists and reduce the diagnostic delay for patients with MPS Ia.

Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias

Genetic skeletal dysplasias (GSDs) are a type of disease with complex phenotype and high heterogeneity, characterized by cartilage and bone growth abnormalities. The variable phenotypes of GSD make clinical diagnosis difficult. To explore the clinical utility of targeted exome sequencing (TES) in the diagnosis of GSD, 223 probands with suspected GSD were enrolled for TES with a panel of 322 known disease-causing genes. After bioinformatics analysis, all candidate variants were prioritized by pathogenicity. Sanger sequencing was used to verify candidate variants in the probands and parents and to trace the source of variants in family members. We identified the molecular diagnoses for 110/223 probands from 24 skeletal disorder groups and confirmed 129 pathogenic/likely pathogenic variants in 48 genes. The overall diagnostic rate was 49%. The molecular diagnostic results modified the diagnosis in 25% of the probands, among which mucopolysaccharidosis and spondylo-epi-metaphyseal dysplasias were more likely to be misdiagnosed. The clinical management of 33% of the probands also improved; 21 families received genetic counseling; 4 families accepted prenatal genetic diagnosis, 1 of which was detected to carry pathogenic variants. The results showed that TES achieved a high diagnostic rate for GSD, helping clinicians confirm patients’ molecular diagnoses, formulate treatment directions, and carry out genetic counseling. TES could be an economical diagnostic method for patients with GSD.

Growth Abnormalities as a Risk Factor of Adverse Neonatal Outcome in Hypertensive Pregnancies—A Single-Center Retrospective Cohort Study

(1) Background: Hypertensive disorders of pregnancy (HDP) include gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE), and preeclampsia superimposed on chronic hypertension (CH with PE). HDP is associated with several short and long-term perinatal and neonatal complications, such as newborn growth restriction and death. This study aimed to establish the association between HDP, newborn growth abnormalities, and neonatal outcome. (2) Methods: This is a single-center retrospective cohort study of 63651 singleton deliveries. (3) Results: Univariate analysis showed a significantly increased risk of intrauterine and neonatal death associated with maternal hypertension and growth disorders. There were differences between growth charts used, with the highest risk of stillbirth for SGA defined by the Intergrowth chart (OR 17.2) and neonatal death for newborn growth restriction (NGR) based on Intergrowth (OR 19.1). Multivariate analysis showed that NGR is a stronger risk factor of neonatal death than SGA only. (4) Conclusions: HDP is significantly associated with growth abnormalities and is an independent risk factor of adverse outcomes. The presence of newborn growth restriction is strongly associated with the risk of neonatal death. The choice of growth chart has a substantial effect on the percentage of diagnosis of SGA and NGR.

The Role of the Adipokines in the Most Common Gestational Complications

Adipocytokines are hormonally active molecules that are believed to play a key role in the regulation of crucial biological processes in the human body. Numerous experimental studies established significant alterations in the adipokine secretion patterns throughout pregnancy. The exact etiology of various gestational complications, such as gestational diabetes, preeclampsia, and fetal growth abnormalities, needs to be fully elucidated. The discovery of adipokines raised questions about their potential contribution to the molecular pathophysiology of those diseases. Multiple studies analyzed their local mRNA expression and circulating protein levels. However, most studies report conflicting results. Several adipokines such as leptin, resistin, irisin, apelin, chemerin, and omentin were proposed as potential novel early markers of heterogeneous gestational complications. The inclusion of the adipokines in the standard predictive multifactorial models could improve their prognostic values. Nonetheless, their independent diagnostic value is mostly insufficient to be implemented into standard clinical practice. Routine assessments of adipokine levels during pregnancy are not recommended in the management of both normal and complicated pregnancies. Based on the animal models (e.g., apelin and its receptors in the rodent preeclampsia models), future implementation of adipokines and their receptors as new therapeutic targets appears promising but requires further validation in humans.