This review categorizes and summarizes the rare pediatric diseases that have been included in the First List of Rare Diseases that was jointly published by the National Health Commission and four other government departments in China in 2018. In total, 58 diseases that develop during childhood are included. These diseases involve nine organ systems, including the musculoskeletal, respiratory, immune, endocrine and metabolic, nervous, cardiovascular, hematological, urinary, and integumentary systems. Affected children often have multiorgan involvement with various presentations. Severe diseases can cause acute symptoms starting in the neonatal period that lead to increased morbidity and mortality without prompt management. Early diagnosis and treatment can significantly change the course of a disease and improve its prognosis. This work systemically reviews the status of rare pediatric diseases with a relatively high incidence in the First List of Rare Diseases.

Many pediatric patients with rare diseases use drugs off-label due to limited data in pediatric patients. Off-label treatment remains an important public health issue for neonates, infants, children, and adolescents, especially for pediatric patients with rare diseases. For patients with rare diseases, the majority of medications have no or limited information in labelling for pediatric use. Children present unique considerations in clinical trials due to ethical and clinical concerns, which have limited and even discouraged testing of drugs in the pediatric population. Numerous legislative measures have been enacted to address barriers in pediatric drug testing. This research reviewed off-label medication use in rare pediatric diseases, evaluated recent medication uses in pediatric clinical practice, discussed key regulations for rare pediatric diseases, and summarized recent drug approvals for rare pediatric diseases. This study demonstrates the ongoing medical need for newly approved medications to treat pediatric rare diseases and revealed the positive impact of regulations from the Orphan Drug Act of 1983 to the Research to Accelerate Cures and Equity (RACE) for Children Act on drug development and off-label medication practice in rare pediatric disease management. This article provides informative historical background and current considerations of off-label use of medications in neonates, infants, children, and adolescents with rare diseases.

Disorders of amino acid and nitrogen metabolism (AANMDs) occur due to an enzyme deficiency in a normal biochemical pathway. Nutritional intervention is recognized as the mainstay of treatment for children diagnosed with AANMD. Hence, this scoping review aimed to identify the nutritional interventions available in managing AANMD disorders and their effects on nutritional status. A systematic search using PRISMA Extension for Scoping Reviews (PRISMA-ScR) method was conducted across 4 databases: PubMed, ScienceDirect (Elsevier), EBSCOhost and Cochrane Central Register of Controlled Trials (CENTRAL). Inclusion criteria for the study to be selected are: subjects aged less than 18-year-old, article published in English, utilized an experimental design and published within the past 20 years. A total of 22 articles were included in this review. The majority of the subjects are boys (55.6%) and employed a randomized controlled trial (RCT) study design (45.4%). Nutritional interventions were categorized into 4 categories which are: "protein substitute" (n = 5), "protein substitute with modified composition" (n = 6), "nutrient supplementation (n=8)", and "distribution and dosage of protein substitute (n = 3)". The most frequently assessed outcomes were biochemical parameters that gauge the effectiveness of metabolic control (68.2%). Overall, "protein substitute enriched with inhibitive amino acids", "long-chain polyunsaturated fatty acids supplementation", and "evenly distributed protein substitute" demonstrated beneficial effects towards the nutritional status, especially in terms of biochemical parameters. In summary, nutritional intervention plays a significant role in improving the nutritional status of AANMD patients. Further investigations of nutritional intervention among AANMD children using a meta-analysis approach are necessary for better comprehension of their impact in management of AANMD disorders.

Alström syndrome is a rare monogenic ciliopathy caused by a mutation to the Alström syndrome 1 (ALMS1) gene. Alström syndrome has an autosomal recessive nature of inheritance. Approximately 1,200 cases of Alström syndrome have been identified worldwide. Complications of the disease are likely caused by dysfunctional cilia with complications arising early in life. The known complications of Alström syndrome have been reported to impact multiple major organ systems, including the endocrine system, cardiac system, renal system, sensory system, and hepatic system. The symptoms of Alström syndrome have great variability in presentation and intensity but often lead to organ damage. This has resulted in a shortened lifespan for individuals affected by Alström syndrome. Individuals with the disease rare exceed the age of 50. Currently, there are no specific treatments for Alström syndrome that can cure the disease, prevent the complications, or reverse the complications. Current management involves management of symptoms with the goal of improving quality of life and lifespan. This review aims to summarize the current knowledge on the epidemiology, diagnosis, pathophysiology, complications, management, and prognosis of Alström syndrome. In addition to that, this review also aims to raise awareness and encourage research on Alström syndrome as the condition has a huge impact on affected individuals.

Marfan syndrome (MFS) is an autosomal hereditary pathology affecting 1:5000 peoples. Alteration of the fibrillin 1 gene (FBN1) results in haplo-insufficiency of the FBN1 protein mainly altering the vascular system. International recommendations have gradually allowed MFS patients to perform training programs because of its potential benefits. However, to date, there are no data on the effect of a long training period in these patients. The aim of the present study is to investigate the effect of a 3-month personalized home-based training on quality of life (QoL) of patients suffering from MFS. At least 50 MFS patients were included in the study. They were randomly placed into 4 groups: control group; endurance; resistance and endurance + resistance training groups. The training program lasted 3 months and is performed at patients' home. There were 2 training sessions per week telemonitored by a specialist of physical activity and cardiology. Pre and post-training evaluations were performed at the Bichat-Paris Hospital, France. They consisted of assessing psychometrics based on self-administered questionnaires (FiRST, GPAQ, ISP-25, MOS SF-36) and physiological parameters such as the peak oxygen consumption, aorta diameter, cardiac ventricle function and skeletal muscle power at rest and during exercise. Our preliminary results showed an improvement of 50% in QoL, cardiorespiratory fitness and skeletal muscle power in a patient who completed the combined training program. This experimental approach might be a new alternative way for MFS patients' care that may improve their QoL, cardiorespiratory fitness and skeletal muscle power.

Duchenne muscular dystrophy (DMD) is a recessive hereditary myopathy due to deficiency of functional dystrophin. Current therapeutic interventions need more investigation to slow down the progression of skeletal and cardiac muscle weakness. In humans, there is a lack of an adapted training program. In animals, the murine Mdx model with a DBA/2J background (D2-mdx) was recently suggested to present pathological features closer to that of humans. In this study, we characterized skeletal and cardiac muscle functions in males and females D2-mdx mice compared to control groups. We also evaluated the impact of high intensity interval training (HIIT) in these muscles in females and males. HIIT was performed 5 times per week during a month on a motorized treadmill. Specific maximal isometric force production and weakness were measured in the tibialis anterior muscle (TA). Sedentary male and female D2-mdx mice produced lower absolute and specific maximal force compared to control mice. Dystrophic mice showed a decline of force generation during repetitive stimulation compared to controls. This reduction was greater for male D2-mdx mice than females. Furthermore, trained D2-mdx males showed an improvement in force generation after the fifth lengthening contraction compared to sedentary D2-mdx males. Moreover, echocardiography measures revealed a decrease in left ventricular end-diastolic volume, left ventricular ejection volume and left ventricular end-diastolic diameter in sedentary male and female D2-mdx mice. Overall, our results showed a serious muscle function alteration in female and male D2-mdx mice compared to controls. HIIT may delay force loss especially in male D2-mdx mice.

Neurofilament Light Chain (NfL) serum concentration is a new noninvasive marker of neurodegenerative disorders. Fabry disease (FD) leads to accumulation of glycosphingolipids in tissues leading to progressive damage of critical body systems and organs, including peripheral and central nervous system. There are no established serum markers of neurodegeneration in FD. Our cross-sectional single-center study was designed to prove the concept that serum NfL levels could reflect the severity of cognitive impairment and indirectly, the level of central nervous system involvement in women at earlier stages of FD. Twelve women with a diagnosis of FD confirmed by genetic tests and 12 matched healthy subjects were included. Serum concentrations of NfL were measured in all subjects together with neuropsychological tests that included Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA). Quality of life was assessed with the Short Form Survey (SF-36). FD patients and healthy subjects did not differ with respect to serum NfL concentration, results of neuropsychological tests and quality of life. There was a significant positive correlation between NfL and globotriaosylosphingosine (lyso-Gb3) concentration in women with FD (R = 0,69, p = 0.01). There was also a correlation between NfL concentration and MoCA score but not MMSE score. Receiver operating characteristic (ROC) analysis showed that the best predictor for Mild Cognitive Impairment in both groups was eGFR. Serum NfL concentration does not appear to predict the degree of nervous system involvement in women with FD.

In Japan, specific pediatric chronic diseases include 788 diseases in 16 groups of diseases, 278 categories, and 845 subcategories as of November 1, 2021. The national specific pediatric chronic diseases measures – also called the Medical Aid Program for Chronic Pediatric Diseases of Specified Categories (MAPChD) – was established in Japan in 1974 and enshrined in law in 2005. Patients with specific pediatric chronic diseases can receive government support and welfare in several ways: i) MAPChD requires diagnosis and medical treatment at designated hospitals and by designated physicians so that patients receive optimal treatment; ii) the copayment rate for medical expenses is reduced to 20% and a maximum is set depending on household income; and iii) the analysis of specific pediatric chronic diseases from different perspectives is continuously being promoted. In addition to these three aspects, various measures are being implemented to provide ongoing support for patients with specific pediatric chronic diseases as they grow up.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disease that affects multiple systems such as the ocular, skeletal, and cardiovascular systems. This disease is relatively rare and has no effective treatment except for symptomatic treatment. As a result, early detection, early intervention, and preventing the occurrence of adverse cardiovascular outcomes are crucial to the diagnosis and treatment of MFS. The rapid development of gene sequencing technology has facilitated the detection of MFS at the genetic level, allowing a more accurate and efficient diagnosis of the disease. Therefore, research on MFS-related genes has become a topic of interest. This article reviews the recent progress of genetic research on MFS in China.

The G protein-coupled estrogen receptor (GPR30) is suggested to exert a role in non-nuclear estrogen signalling and is over-expressed in a variety of hormone dependent tumors. It is well known that estrogens and xenoestrogens are involved in testicular germ cell tumorigenesis. Different studies show that down regulation of estrogen receptor β (ERβ) associates with GPR30 over-expression both in human testicular carcinoma in situ (CIS) and seminomas and that the mitogenic role exerted by 17β-oestradiol induces the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) through GPR30. In conclusion, the exposure to oestrogens or oestrogen-mimics, in some as of yet undefined manner, diminishes the ERβ-mediated growth restraint in CIS and in human testicular seminoma, indicating that GPR30 could be considered a potential therapeutic target to design specific inhibitors.