Duchenne muscular dystrophy (DMD) is a severe and progressively debilitating X-linked recessive disorder caused by mutations in the DMD gene, which encodes the dystrophin protein. This deficiency in dystrophin results in the progressive degeneration of both skeletal and cardiac muscles. Currently, there is no definitive cure for DMD, and treatment primarily aims to slow disease progression and manage symptoms. With the widespread application of respiratory support measures, DMD cardiomyopathy has emerged as the primary contributor to morbidity and mortality among DMD patients at present. There is an acute and pressing need to develop highly effective therapeutic strategies for treating DMD cardiomyopathy and to prevent the onset of heart failure. Various hypotheses have been proposed to explain the underlying mechanisms, including elevated levels of inflammatory cytokines, dysregulated HDAC activity, disruptions in ion balance, and mitochondrial dysfunction, which is also considered a potentially significant contributor. This review article aims to provide a comprehensive overview of various animal and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) models on DMD and DMD cardiomyopathy. It also provides a summary of current advancements and ongoing efforts in the treatment of DMD and DMD-related cardiomyopathy, with a focus on innovative treatment modalities, such as mitochondria transplantation or targeting ion homeostasis. This underscores the dynamic and evolving nature of research dedicated to developing effective treatments for DMD and DMD cardiomyopathy.
Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and skin and/or tendon xanthomas. FH is caused by mutations in genes associated with the LDL receptor pathway. Heterozygous FH is frequently encountered, occurring in about one in 300 people, one in 30 people with coronary artery disease, and one in 15 people with premature coronary artery disease or severe hyperlipidemia. Because FH patients are exposed to high LDL-C concentrations from birth, this leads to progressive atherosclerosis, and the development of cardiovascular events in these patients is
Aim: Familial hypercholesterolaemia (FH), an autosomal-dominant disorder, requires early diagnosis to prevent atherosclerosis in children and coronary artery disease (CAD) in their parents. This study aimed to evaluate the effectiveness and barriers of reverse cascade screening (RCS) combined with universal cholesterol screening (UCS) for paediatric FH.
Methods: We performed RCS combined with UCS for paediatric FH between January 2018 and July 2023. Family pedigree was evaluated in second-degree relatives, using a child with a genetic diagnosis of FH as the proband. Based on the 2022 Japan Atherosclerosis Society clinical guidelines, cases with suspected FH were classified into four categories: “Definite”, “Probable”, “Possible”, or “Unlikely”. Those who did not complete the diagnostic process were evaluated based on the reasons, including challenges such as “Untested lipids in children”, “Bereavement”, “CAD with unspecified details”, “Dyslipidaemia with unspecified low-density lipoprotein cholesterol (LDL-C) levels”, and “No information on CAD or dyslipidaemia”.
Results: Of 252 patients suspected of having FH, 94 completed the diagnostic process. Among them, 49 were classified as “Definite” FH cases, predominantly among first-degree relatives. In contrast, 158 patients did not complete the diagnostic process, with the most common barriers being “Dyslipidaemia with unspecified LDL-C levels” and “No information on CAD or dyslipidaemia”, particularly among second-degree relatives.
Conclusion: RCS combined with UCS for paediatric FH using genetic testing is effective for the early diagnosis of FH in asymptomatic cases. However, addressing barriers that hinder FH diagnosis, such as difficulties in approaching second-degree relatives, is critical for improving diagnosis rates.
Myasthenia gravis (MG) is an autoimmune disease primarily affecting the neuromuscular junction. Its main clinical manifestations are fluctuating muscle weakness and easy fatigability, which are currently believed to be caused by disease-specific autoantibodies. Pharmacological therapy is the first-line treatment for MG, and treatment regimens including glucocorticoids, immunosuppressants, and pyridostigmine are considered to significantly improve patients’ clinical manifestations, enabling patients to achieve the treatment goal of minimal manifestation status (MMS). Supportive therapy is also considered equally important in clinical practice. Traditionally, it was thought that exercise might exacerbate symptoms in MG patients; however, with a deeper understanding of MG and the publication of relevant research findings, it is now believed that moderate exercise can benefit stable MG patients.
Systemic lupus erythematosus (SLE) poses significant diagnostic challenges. First, it is characterized by a highly variable combination of autoantibodies and a wide range of possible organ involvement and symptoms. Second, no single laboratory test can definitively confirm or exclude the diagnosis. Third, due to the low incidence of SLE, clinicians must carefully balance considering SLE as a potential diagnosis against more common causes of similar symptoms. The joint European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria provide a helpful framework for thinking about SLE diagnosis, although they are not intended for diagnostic use. Nevertheless, several elements of the criteria - such as the requirement for anti-nuclear antibodies (ANA) positivity as an entry point (similar to a screening test), the weighted scoring of clinical and immunological features, and the attribution of findings to SLE only when no more likely alternative explanation exists - highlight principles that are also useful in the diagnostic process. Conceptionally, diagnosing SLE can be seen as a three-step process: (1) considering the possibility of SLE; (2) systematically collecting evidence for or against the diagnosis; and (3) making a diagnostic decision based on whether the accumulated evidence sufficiently supports or refutes the diagnosis. This review follows the three-step framework in discussing the clinical diagnosis of SLE clinical diagnosis.
Aim: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioral problems, and hypothalamic dysfunction combined with specific dysmorphisms. PWS is associated with limited adult height and an unfavorable body composition. Premature pubarche is frequent. Data on adult height after long-term growth hormone therapy are limited, as are data on the development of body composition during growth hormone therapy and the role of premature pubarche. This study aimed to explore the effect of long-term growth hormone therapy on adult height and body composition at adult height in children with PWS.
Methods: This was a single-center, retrospective descriptive study involving 24 boys and 20 girls with genetically confirmed PWS. All participants began growth hormone therapy in early childhood until they reached adult height (AH). The children received internationally standardized growth hormone therapy. The primary outcome measures were AH, lean mass (LM), and fat mass (FM), as determined by dual-energy X-ray absorptiometry.
Results: Adult height was 172.4 cm (-0.87 SD) in males and 160 cm (-0.90 SD) in females. There was no difference between children with or without premature pubarche. At adult height, LM was normal, but FM was increased in both males and females.
Conclusion: Boys with PWS reached a normal height compared to their families; in girls, AH was just below the target height. AH did not differ between children with or without premature pubarche. LM was normal but should probably be higher, given the overweight, and FM was still increased after long-term growth hormone therapy.