Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors?

Background: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations.

Methods: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011).

Neighborhood-level Socioeconomic Position During Early Pregnancy and Risk of Gastroschisis.

Background: Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the un derstudied association between neighborhood-level socioeconomic position during early pregnancy and the risk of gastroschisis, an abdominal birth defect of increasing prevalence.

Methods: We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997-2011).

An Age-Based Framework for Evaluating Genome-Scale Sequencing Results in Newborn Screening.

Objective: To assess the performance of a standardized, age-based metric for scoring clinical actionability to evaluate conditions for inclusion in newborn screening and compare it with the results from other contemporary methods.

Study Design: The North Carolina Newborn Exome Sequencing for Universal Screening study developed an age-based, semiquantitative metric to assess the clinical actionability of gene-disease pairs and classify them with respect to age of onset or timing of interventions. This categorization was compared with the gold standard Recommended Uniform Screening Panel and other methods to evaluate gene-disease pairs for newborn genomic sequencing.

Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations.

Tyrosinemia type I (hepatorenal tyrosinemia, HT-1) is an autosomal recessive condition resulting in hepatic failure with comorbidities involving the renal and neurologic systems and long term risks for hepatocellular carcinoma. An effective medical treatment with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC) exists but requires early identification of affected children for optimal long-term results. Newborn screening (NBS) utilizing blood succinylacetone as the NBS marker is superior to observing tyrosine levels as a way of identifying neonates with HT-1.

Co-occurring Down syndrome and SUCLA2-related mitochondrial depletion syndrome.

Mitochondrial DNA depletion syndrome 5 (MIM 612073) is a rare autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the beta subunit of the succinate-CoA ligase gene located within the 13q14 band. We describe two siblings of Hispanic descent with SUCLA2-related mitochondrial depletion syndrome (encephalomyopathic form with methylmalonic aciduria); the older sibling is additionally affected with trisomy 21. SUCLA2 sequencing identified homozygous p.

Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia.

Dienoyl-CoA reductase (DECR) deficiency with hyperlysinemia is a rare disorder affecting the metabolism of polyunsaturated fatty acids and lysine. The molecular basis of this condition is currently unknown. We describe a new case with failure to thrive, developmental delay, lactic acidosis and severe encephalopathy suggestive of a mitochondrial disorder.

Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome.

Purpose: This study evaluated the safety and effectiveness of long-term enzyme replacement therapy with idursulfase (recombinant human iduronate-2-sulfatase) in patients with Hunter syndrome.

Methods: All 94 patients who completed a 53-week double-blinded study of idursulfase enrolled in this open-labeled extension study and received intravenous idursulfase at a dose of 0.5 mg/kg weekly for 2 years, and clinical outcomes and safety were assessed.

Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig): sibs with a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital malformations, and early lethality.

In this report, we describe a brother and sister who presented at birth with short-limb skeletal dysplasia, polyhydramnios, prematurity, and generalized edema. Dysmorphic features included broad nose, thick ears, thin lips, micrognathia, inverted nipples, ulnar deviation at the wrists, spatulate fingers, fifth finger camptodactyly, nail hypoplasia, and talipes equinovarus. Other features included short stature, microcephaly, psychomotor retardation, B-cell lymphopenic hypogammaglobulinemia, sensorineural deafness, retinal detachment and blindness, intestinal malrotation with poor gastrointestinal motility, persistent hyponatremia, intermittent hypoglycemia, and thrombocytopenia.

A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome).

Objective: To evaluate the safety and explore the efficacy of idursulfase (recombinant human iduronate-2-sulfatase) treatment for mucopolysaccharidosis II (MPS II).

Study Design: Twelve patients were enrolled into a randomized, double-blind, placebo-controlled trial for 24 weeks followed by an open-label extension study. Three groups of 4 patients were enrolled sequentially, with 3 patients in each group receiving idursulfase and 1 patient receiving placebo.

A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome).

Purpose: To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II.

Methods: Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.