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Objective: Clinical and genetic heterogeneities make diagnosis of limb‐girdle muscular dystrophy (LGMD) and other overlapping disorders of muscle weakness complicated and expensive. We aimed to develop a comprehensive next generation sequence‐based multi‐gene panel ("The Lantern Focused Neuromuscular Panel") to detect both sequence variants and copy number variants in one assay. Methods: Patients with clinical diagnosis of LGMD or other overlapping muscular dystrophies in the United States were tested by PerkinElmer Genomics in 2018–2021 via "The Lantern Project," a sponsored diagnostic testing program. Sixty‐six genes related to LGMD subtypes‐ and other myopathies were investigated. Main outcomes were diagnostic yield, gene‐variant spectrum, and LGMD subtypes' prevalence. Results: Molecular diagnosis was established in 19.6% (1266) of 6473 cases. Major genes contributing to LGMD were identified including CAPN3 (5.4%, 68), DYSF (4.0%, 51), GAA (3.7%, 47), ANO5 (3.6%, 45), and FKRP (2.7%, 34). Genes of other overlapping MD subtypes identified included PABPN1 (10.5%, 133), VCP (2.2%, 28), MYOT (1.2% 15), LDB3 (1.0%, 13), COL6A1 (1.5%, 19), FLNC (1.1%, 14), and DNAJB6 (0.8%, 10). Different sizes of copy number variants including single exon, multi‐exon, and whole genes were identified in 7.5% (95) cases in genes including DMD, EMD, CAPN3, ANO5, SGCG, COL6A2, DOK7, and LAMA2. Interpretation: "The Lantern Focused Neuromuscular Panel" enables identification of LGMD subtypes and other myopathies with overlapping clinical features. Prevalence of some MD subtypes was higher than previously reported. Widespread deployment of this comprehensive NGS panel has the potential to ensure early, accurate diagnosis as well as re‐define MD epidemiology. [ABSTRACT FROM AUTHOR]

Nutritional management of patients who have urea cycle disorders is one of the most challenging tasks in clinical nutrition. The degree to which protein intake should be restricted in urea cycle disorders requires complex calculations which depend on many variables such as specific enzyme defect, age-related growth rate, current health status, level of physical activity, amount of free amino acids administered, energy intake, residual urea cycle function, family lifestyle, use of nitrogen-scavenging medications, and the patient's eating behaviors. This paper presents two case histories and a series of recommendations outlining the nutrition management of urea cycle disorders. It also identifies difficulties that arise in the course of treatment, and suggests practical solutions for overcoming them.

The goal of counseling families that have a urea cycle disorder (UCD) is to facilitate the process of scientific understanding, emotional acceptance, and decision-making in a nondirective way. A proper understanding of the genes involved, inheritance patterns, available testing, and complicating factors is critical to serving the families' needs. This article summarizes the needed information, in particular describing the complexities of prenatal testing and counseling issues for each UCD. Included case histories illustrate the genetic counseling process and the decision-making scenarios for two families.