OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

This study investigates the reproductive protective effect and potential mechanism of Cistanches Herba extract(CHE) on a rat model of kidney-Yang deficiency induced by adenine. Rats were randomly divided into five groups: normal, model, low-dose CHE(0.6 g·kg~(-1)·d~(-1)), high-dose CHE(1.2 g·kg~(-1)·d~(-1)), and L-carnitine(100 mg·kg~(-1)·d~(-1)). The rats were administered adenine(200 mg·kg~(-1)·d~(-1)) by gavage for the first 14 days to induce kidney-Yang deficiency, while simultaneously receiving drug treatment. After 14 days, the modeling was discontinued, but drug treatment continued to 49 days. The content of components in CHE was analyzed by high-performance liquid chromatography. The adenine-induced kidney-Yang deficiency model was assessed through symptom characterization and measurement of testosterone(T) levels using an enzyme-linked immunosorbent assay kit. Pathological damage to the testis and epididymis was evaluated based on the wet weight and performing hematoxylin-eosin staining. Sperm density and motility were measured using computer-aided sperm analysis, and sperm viability was assessed using live/dead sperm staining kits, and sperm morphology was evaluated using eosin staining, thereby determining rat sperm quality. Metabolomics was used to analyze changes in serum metabolites, enrich related metabolic pathways, and explore the mechanism of CHE in improving reproductive function damage in rats with kidney-Yang deficiency syndrome. Compared to the normal group, the model group exhibited significant kidney-Yang deficiency symptoms, reduced T levels, decreased testicular and epididymal wet weights, and significant pathological damage to the testis and epididymis. The sperm density, motility, and viability decreased, with an increased rate of sperm abnormalities. In contrast, rats treated with CHE showed marked improvements in kidney-Yang deficiency symptoms, restored T levels, alleviated pathological damage to the testis and epididymis, and improved various sperm parameters. Metabolomics results revealed 286 differential metabolites between the normal and model groups(191 upregulated and 95 downregulated). Seventy-five differential metabolites were identified between the model and low-dose CHE groups(21 upregulated and 54 downregulated). A total of 24 common differential metabolites were identified across the three groups, with 22 of these metabolites exhibiting opposite regulation trends between the two comparison groups. These metabolites were primarily involved in linoleic acid metabolism, ether lipid metabolism, and pantothenic acid and coenzyme A biosynthesis, as well as metabolites including 13-hydroperoxylinoleic acid, lysophosphatidylcholine, and pantethine. CHE can improve kidney-Yang deficiency symptoms in rats, alleviate reproductive organ damage, and enhance sperm quality. The regulation of lipid metabolism may be a potential mechanism through which CHE improves reproductive function in rats with kidney-Yang deficiency. The potential bioactive compounds of CHE include echinacoside, verbascoside, salidroside, betaine, and cistanoside A.
Animals ; Male ; Rats ; Yang Deficiency/physiopathology* ; Metabolomics ; Kidney/physiopathology* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Cistanche/chemistry* ; Kidney Diseases/metabolism* ; Testis/metabolism* ; Humans ; Reproduction/drug effects* ; Testosterone/blood*

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

OBJECTIVE: To investigate the results of preimplantation genetic testing for monogenic diseases (PGT-M) in a Chinese pedigree affected with Primary carnitine deficiency (PCD). METHODS: A pedigree affected with PCD who visited Hainan Women and Children's Medical Center in April 2023 due to "SLC22A5 gene mutation found in offspring genetic testing and preparing for a second child" was selected as the study subject. Pathogenicity of the proband's variant sites was determined by referring to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG). Sanger sequencing was used to verify the variant sites of SLC22A5 gene in the proband and her parents, and the single nucleotide polymorphism (SNP) haplotype of the family was constructed by SNP microarray (SNP array) method to determine the carrier status of pathogenic genes. After fertilization via assisted reproductive technology, whole genome amplification (WGA) was performed on the biopsied trophoblastic cells. Sanger sequencing, next-generation sequencing (NGS), and SNP array techniques were then used to detect the variants in the SLC22A5 gene and chromosome copy number variation (CNV) in the embryos. Embryos without the variants were selected for transferring. After the successful pregnancy of the proband's mother, amniocentesis was not performed for prenatal diagnosis due to repeated vaginal bleeding. After delivery, neonatal peripheral blood sample was collected to verify the results of PGT-M, and follow-up was conducted. This study was reviewed and approved by the Medical Ethics Committee of Hainan Women and Children's Medical Center (Ethics No. HNWCMC-2022-178). RESULTS: In this study, the c.338G>A and c.760C>T variants in SLC22A5 gene were evaluated as pathogenic variants. Sanger sequencing results of this family showed that the c.338G>A and c.760C>T variants of the proband were inherited from his father and mother, respectively. Haplotypes of c.338G>A and c.760C>T variants of SLC22A5 gene were successfully constructed. PGT-M results showed that 2 of the 8 blastulas biopsied failed WGA, and the CNV detection results of the remaining 6 blastocysts were all euploid: 2 had no mutations in the SLC22A5 gene, 3 were single heterozygous carriers of paternal or maternal origin, and 1 was compound heterozygous carriers of paternal and maternal origin. Combined with the embryo morphology score, an intrauterine singleton pregnancy was achieved after the successful transfer of an optimal embryo with no CNV abnormalities and no paternal or maternal SLC22A5 gene mutations, resulting in the birth of a healthy female baby at 38⁺³ weeks of gestation. The results of peripheral blood chromosomal karyotyping analysis, CNV detection and SLC22A5 gene c.338G>A and c.760C>T site variant detection of the infant were consistent with those of PGT-M, and no abnormality was found. CONCLUSION PGT-M had helped the couple carrying SLC22A5 gene variant to have a healthy offspring and effectively blocked the transmission of PCD in this family.
Adult ; Female ; Humans ; Male ; Pregnancy ; Cardiomyopathies ; China ; East Asian People/genetics* ; Genetic Testing/methods* ; High-Throughput Nucleotide Sequencing ; Hyperammonemia/genetics* ; Mutation ; Pedigree ; Polymorphism, Single Nucleotide ; Preimplantation Diagnosis/methods* ; Solute Carrier Family 22 Member 5/genetics* ; Carnitine/deficiency* ; Muscular Diseases

A boy, aged 16 months, attended the hospital due to head and facial erythema for 15 months and vulva erythema for 10 months with aggravation for 5 days. The boy developed perioral and periocular erythema in the neonatal period and had erythema and papules with desquamation and erosion in the neck, armpit, and trigone of vulva in infancy. Blood gas analysis showed metabolic acidosis; the analysis of amino acid and acylcarnitine profiles for inherited metabolic diseases and the analysis of organic acid in urine suggested multiple carboxylase deficiency; genetic testing showed a homozygous mutation of c.1522C>T(p.R508W) in the HLCS gene. Finally the boy was diagnosed with holocarboxylase synthetase deficiency and achieved a good clinical outcome after oral biotin treatment. This article analyzes the clinical data of a child with holocarboxylase synthetase deficiency and summarizes the etiology, diagnosis, and treatment of this child, so as to provide ideas for clinicians to diagnose this rare disease.
Humans ; Male ; Biotin/therapeutic use* ; Holocarboxylase Synthetase Deficiency/drug therapy* ; Homozygote ; Mutation ; Rare Diseases/drug therapy* ; Infant

Primary immunodeficiency diseases (PID) is a congenital disease caused by single gene germline mutation related to the immune system. PID patients have immune dysregulation, and are susceptible to infectious diseases, autoimmune diseases, autoimmune diseases, allergic diseases, and malignant tumors. The first symptom of some PID patients is atopic disease, therefore they go to the department of allergy, department of pediatrics and other relevant departments. How to identify and diagnose PID in allergic patients, to reduce diagnosis delay and prevent disease aggravation are the abilities that allergists, pediatricians, and doctors in other relevant departments need to master. This article summarizes the warning signs of PID in allergic patients and the mechanism of allergy combined with PID, and then summarizes the common types of PID in allergic patients, the evaluation, treatment and prevention in patients with PID and allergy.
Autoimmune Diseases ; Child ; Humans ; Hypersensitivity/therapy* ; Immunologic Deficiency Syndromes/therapy* ; Primary Immunodeficiency Diseases/therapy*

OBJECTIVE: To analyze the metabolic profile and genetic variants for newborns with primary carnitine deficiency (PCD) from Guangxi, China. METHODS: From January 2014 to December 2019, 400 575 newborns from the jurisdiction of Guangxi Zhuang Autonomous Region Newborn Screening Center were subjected to tandem mass spectrometry (MS/MS) analysis. Newborns with positive results for PCD and their mothers were recalled for retesting. Those who were still positive were subjected to sequencing of the SLC22A5 gene. RESULTS: Twenty-two newborns and 9 mothers were diagnosed with PCD, which gave a prevalence rate of 1/18 208. Sequencing of 18 newborns and 4 mothers have identified 14 types of SLC22A5 gene variants, with the common ones including c.51C>G (10/44, 22.7%), c.1195C>T (9/44, 20.5%) and c.1400C>G (7/44, 15.9%), The c.517delC(p.L173Cfs*3) and c.1031C>T(p.T344I) were unreported previously and predicted to be pathogenic (PVS1+PM2_supporting+PM3+PP4) and likely pathogenic (PM1+PM2_supporting+PM3+PP3+PP4) based on the American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION c.51C>G, c.1195C>T and c.1400C>G are the most common variants underlying PCD in Guangxi.
Cardiomyopathies ; Carnitine/deficiency* ; China ; Humans ; Hyperammonemia ; Infant, Newborn ; Metabolome ; Muscular Diseases ; Mutation ; Solute Carrier Family 22 Member 5/genetics* ; Tandem Mass Spectrometry

To investigate the clinical characteristics and the rule of administration of Ciwujia Injection in patients with cardiovascular disease by correlation analysis and frequency analysis. The information of 5 904 patients who used Ciwujia Injection to treat cardiovascular disease for at least three times in the hospital information system(HIS) of 19 comprehensive tertiary hospitals nationwide. The frequency analysis method was used to analyze the higher frequency variables, and the algorithm of Apriori correlation analysis method was used to analyze the clinical characteristics and medication laws of Ciwujia Injection in treating patients with cardiovascular disease. Among the 5 904 patients, the median age of the patients was 70 years, and the number of patients between 65-75 years old was up to 2 096(35.5%). There were more women than men in terms of diagnosis and treatment, and the women at age of 45-65 and 65-75 years old were more than men. The top three diagnoses by Western medicine were coronary heart disease in 8 104 cases(65.66%), dyslipidemia in 2 515 cases(20.38%), and cardiac function grade Ⅱ-Ⅲ in 581 cases(4.71%), while the largest number of syndromes in traditional Chinese medicine(TCM) at discharge was 1 109(21.37%) in other type, followed by 739 cases(14.24%) of Qi deficiency and blood stasis syndrome, and 698(13.46%) of liver and kidney Yin deficiency syndrome. The most frequently used Western medicine in combined use was Nifedipine in 2 567 cases(7.21%), and most frequently used TCM was Compound Xianzhuli Liquid leachate in 766 cases(3.53%). From the results of pharmacological analysis, the frequency of using Ciwujia Injection + stasi-seliminating agent + calcium channel blocking drugs was highest when using 1 Chinese medicine combined with 1 or 2 Western medicines. In the use of 2 Chinese medicines combined with 1 Western medicine, Ciwujia Injection + heat-clearing agent + stasis-eliminating agent + calcium channel blocker was the most common. This study demonstrated that Ciwujia Injection was more common in middle-aged and elderly patients and more in women than men. Treatment should be based on different cardiovascular disease treatment guidelines to reduce complications caused by underlying diseases, and attention should be paid to the prevention and treatment of cardio-vascular disease risk factors such as hypertension, diabetes and abnormal lipid metabolism. According to the analysis of frequency distribution and association rules, it was concluded that Ciwujia Injection was mainly used in combination with calcium channel blockers and stasis-eliminating agents in the treatment of cardiovascular disease. In the treatment of cardiovascular diseases by Ciwujia Injection in combination with other Chinese and Western medicines, in order to avoid pharmacological changes and avoid affecting the efficacy of the drug, it is necessary to closely observe whether adverse reactions occur and ensure that the medication is safe and effective. This study provides a good reference for the follow-up clinical guidance of Ciwujia Injection.
Aged ; Cardiovascular Diseases ; Drugs, Chinese Herbal ; Eleutherococcus ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Yin Deficiency

Ornithine transcarbamylase deficiency(OTCD)is a most common ornithine cycle (urea cycle) disorder. It is a X-link inherited disorder caused by
Humans ; Hyperammonemia/etiology* ; Liver Transplantation ; Nervous System Diseases/prevention & control* ; Ornithine Carbamoyltransferase Deficiency Disease/therapy*