Molecular and cellular pediatrics最新文献

Background: This study aimed to identify GBA1 variants in Egyptian Gaucher disease (GD) patients residing in a region with high consanguinity and to correlate these genotypes with their clinical phenotypes.

Methodology: This descriptive study included 68 Egyptian patients diagnosed with GD. Diagnosis relied upon reduced β-glucocerebrosidase activity measured by tandem mass spectrometry from dried blood spots and confirmed by GBA1 single-gene sequencing. Clinical and laboratory information were gathered from patient records, and neurological evaluations were conducted by a neurologist.

Results: Thirty patients (44.1%) were classified as type 1 GD, three (4.4%) as type 2 GD, and 35 patients (51.5%) as type 3 GD. Variant analysis of the 136 alleles identified 19 different variants. The most prevalent mutant allele was c.1448T > C p.(Leu483Pro) (50.7%). Seven novel variants were documented: five homozygous missense variants, including c.263 C > T p.(Met88Thr), c.1331 A > G p.(Asp444Gly), c.1409 C > T p.(Ser470Phe), c.907 C > G p.(Leu303Val), c.1574G > A p.(Gly525Asp), two heterozygous missense variants: c.380 C > G p.(Ala127Gly) and c.453 + 2T > C. All carriers of these novel variants were phenotypically classified as type 1 GD. Genotype-phenotype correlations confirmed that the c.1226 A > G p.(Asn409Ser) variant was confined to type 1 GD, whereas c.1448T > C p.(Leu483Pro) was associated with types 2 and 3 GD.

Conclusion: Variant analysis of 136 alleles identified 19 GBA1 variants, including seven novel variants. These findings enhance genotype-phenotype correlations, provide genetic counseling, and enable customized molecular analyses for families at risk.

Background: Late preterm infants (34-36 weeks gestation) represent the majority of preterm births and are often assumed to follow similar postnatal growth trajectories as term infants. However, the postnatal hormonal environment and body composition development in this group remain underexplored. This prospective observational study aimed to analyze and compare growth, body composition, energy expenditure, hormonal, and metabolic responses in healthy late preterm and term infants in the first four months of life.

Results: Anthropometry, body composition, energy expenditure, metabolic biomarkers and growth factors were measured in 94 term infants (gestational age: 39.6 ± 1.3 weeks, birth weight 3330 ± 570 g) and 18 late preterm infants (35.0 ± 1.0 weeks, 2520 ± 660 g) at three time points (0-5, 55-65 and 115-125 days of life). The onset of fat mass accretion occurred directly after birth resulting in higher percent fat mass in late preterm infants in early life. Late preterm infants reached a similar percent fat mass approximately five weeks earlier in postmenstrual age than term infants. In contrast, fat-free mass developed along similar trajectories in both groups, indicating preserved lean tissue growth in late preterm infants. Energy expenditure doubled during the first two months and was closely linked to fat-free mass accretion. Insulin-like growth factor (IGF)-1 and IGF-2 levels increased postnatally, with slightly higher concentrations in late preterm infants. Increase of percent fat mass paralleled leptin and IGF levels in both groups. IGF-1 and IGF-2 levels were higher in formula-fed infants, supporting the influence of nutritional composition on growth-related hormonal regulation.

Conclusions: Birth may initiate changes in hormonal levels and acceleration of fat mass accrual, resulting in higher fat mass in late preterm-born infants at term age when compared to term-born infants. Next to hormonal shifts, these changes appear to be driven by nutritional factors in the early postnatal period. The results suggest that growth targets for late preterm infants may need to be reconsidered, particularly in the early postnatal period. Future studies should provide evidence on individual growth targets and nutritional guidelines for preterm infants to account for the physiological differences to term infants.

The new German Center for Child and Adolescent Health (DZKJ) founded as part of the German Centers for Health Research provides an unprecedented and unique opportunity for internationally outstanding research that contributes to the health and well-being of children and adolescents by creating a sustainable, multidisciplinary translational research center with a wide spectrum of clinical and scientific disciplines. The DZKJ attracts and motivates some of the best basic and clinical scientists in Germany inside and outside the field of pediatrics to jointly dedicate their research and creativity to unravelling the causes of both common and rare diseases and to developing innovative therapies and prevention strategies. All DZKJ partner sites will join forces for a pivotal, networked lighthouse for clinical and translational science in pediatrics in Germany and beyond.

Background: Thrombocytopenia is the most common hematologic manifestation of acid sphingomyelinase deficiency (ASMD). The introduction of enzyme replacement therapy (ERT) represents significant progress in the treatment landscape of this disorder. This study presents the largest pediatric case series of ASMD to date, providing valuable insights into the real-world application of ERT in affected children.

Methods: Ten children with ASMD (five with type B and five with type A/B) received ERT for one year. Growth parameters, complete blood counts, abdominal ultrasonography, liver function tests, lipid profiles, and neurological assessments were conducted at baseline and subsequently every three months. In addition, chest high-resolution computed tomography (HRCT) and dual-energy X-ray absorptiometry (DXA) were performed at baseline and repeated after one year.

Results: No serious infusion-related reactions (IAR) were recorded. However, one patient developed a mild urticarial rash, while another experienced pyrexia. Anemia was present in all children at baseline. A significant increase in hemoglobin levels starting at week 12 (p = 0.02) with peak levels observed at week 50. Thrombocytopenia was present in 60% of patients at baseline. Platelet counts did not show a significant change at week 12 (p = 0.3), but a significant increase was observed after 24 weeks (p = 0.0196), and counts peaked at week 50 (p = 0.0057). There was a significant reduction in liver and spleen sizes, as well as lipid profile parameters. In addition, gradual improvements were observed in interstitial lung disease scores and bone mineral densities throughout the study course.

Conclusion: Our findings indicate that olipudase alfa provides significant benefits in key hematological and visceral clinical outcomes in pediatric patients with ASMD.

This report describes the case of a 25-year-old female patient with multicentric infantile myofibromatosis since early infancy, superficial capillary malformations and congenital hypoplasia of the third and fourth finger of her right hand. All known lesions were located in the upper extremities, the chest and the upper back. A pathogenic, gain-of-function platelet-derived growth factor receptor-beta (PDGFRB) variant (p.N666K, c.1998 C > A) was detected in two myofibromas and in a capillary malformation on the upper back, but not in DNA obtained from blood mononuclear cells. Thus, PDGFRB mosaicism appears to account for the patient's myofibromas and capillary malformations, supporting a broad spectrum of PDGFRB-driven anomalies ranging from myofibromas to vascular malformations.

Background: DeSanto-Shinawi Syndrome (DESSH) is a rare neurodevelopmental disorder characterized by intellectual disability, behavioral abnormalities, and distinctive dysmorphic features, linked to likely pathogenic/pathogenic variants in the WAC gene. We report the first documented case of DESSH in India, identified in a 3-year-old male presenting with global developmental delay and coarse facies.

Results: Exome sequencing revealed a novel heterozygous nonsense likely pathogenic variant (c.1661 C>A(p.Ser554*)) in the WAC gene, expanding the genotypic spectrum associated with this condition. We employed computational methodologies to understand the effects of this novel variant on protein structure and function. In-silico prediction score suggested protein truncation due to the c.1661 C>A (p.Ser554*) variation in the WAC gene, expected to result in a loss of normal protein function.

Conclusion: The findings advocate for increased awareness and genetic testing in atypical cases to facilitate accurate diagnosis and management. This case underscores the importance of considering DESSH in the differential diagnosis of similar neurodevelopmental disorders and enhances our understanding of the genetic diversity within the WAC gene.