OBJECTIVE: To explore the genetic etiology of a child with Renpenning syndrome (RS), and review the literature on the clinical characteristics and gene mutations of RS. METHODS: A child with RS (patient 1) who was diagnosed and treated in the Pediatric Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University in November 2023 was selected as the research object. The medical history, family history, physical examination, cerebrospinal fluid examination, echocardiography, brain magnetic resonance imaging (MRI), brain magnetic resonance angiography, cardiac coronary CT angiography and intelligence quotient (IQ) score of child 1 were retrospectively collected. Peripheral venous blood samples were collected from patient 1, his parents, sister and brother, respectively. Genomic DNA was extracted from the child and his family members, and Trios-whole exome sequencing (Trios-WES) was performed. Sanger sequencing was used to verify the pedigree. Bioinformatics softwares (Mutation Taster, REVEL, SIFT, PolyPhen-2, GERP++, SWISS-MODEL) were applied. The pathogenicity of the detected variants was rated according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the ACMG Guidelines). "PQBP1 gene" "Renpenning syndrome" "PQBP1 gene" "Renpenning syndrome" were used as keywords in Chinese and English, respectively. Case reports of patients with RS caused by PQBP1 gene variants were retrieved from Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed database. The clinical features and gene variants of RS caused by PQBP1 gene variants were summarized and analyzed. This study was reviewed by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Approval No. 2024-334-01). RESULTS The patient 1, a 12-year-old boy, was admitted to the hospital due to fever and disturbance of consciousness. Cerebrospinal fluid test showed viral encephalitis caused by human herpesvirus 7 infection. The main clinical manifestations were unusual facies (microcephaly, long narrow face, microphthalmos, superior oblique palpebral fissure, hypertelorism of inner canthus, bulbous nasal columella) and mental retardation. Auxiliary examination showed than patient 1 had atrial septal defect, nodular heterotopia in the posterior horn of the left ventricle, angiodysplasia, and low IQ. The disease began in infancy, and there was no family history of related diseases. A hemizygous deletion, c.459_462del (p.Arg153SerfsTer41), was identified in exon 5 of the PQBP1 gene in patient 1, which was inherited from his mother by Sanger sequencing. The results of bioinformatics analysis showed that the mutation was harmful. This variant was rated as pathogenic (PVS1+PS4+PM2_Supporting+PP3) according to ACMG Guidelines. According to the literature search strategy set in this study, a total of 13 cases of RS were retrieved, involving 16 cases of RS patient caused by PQBP1 gene mutation (patients 2-17), including patient 1, a total of 17 cases of RS. Among the 17 patients, 16 male patients had hemizygous mutations in the X chromosome PQBP1 gene, and 1 female patient had heterozygous mutations, including 12 deletion frameshift nonsense mutations, 3 point missense mutations, and 2 duplication mutations. Except for two fetuses, all patients had special facial features and low IQ to varying degrees. Ten patients had abnormal development of one or more organs such as eyes, heart, brain, etc. CONCLUSION: The main clinical manifestations of RS are developmental delay, long narrow face, bulbous nose, microcephaly, and may be accompanied by heterotopia of gray matter of ventricle and congenital heart disease. The c.459_462del (p.Arg153SerfsTer41) variant of the PQBP1 gene is the genetic basis of patient 1 in this study.
Humans ; Male ; Mutation ; Pedigree ; Child ; DNA-Binding Proteins/genetics* ; Nuclear Proteins/genetics* ; Female ; Exome Sequencing

Objective:To summarize the clinical and genetic characteristics of children with Menkes disease(MD).Methods:The clinical manifestations, auxiliary examinations and genetic testing results of 15 MD children admitted to the Department of Pediatrics of the Third Affiliated Hospital of Zhengzhou University, Children′s Hospital Affiliated of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from June 2016 to October 2022 were analyzed retrospectively.These children were followed up.Results:All the 15 children were male.The age at onset was ranging from 9 days to 5.5 months.White skin, curly hair, skin laxity, hypotonia and severe developmental delay were found in all children, with epilepsy in 13 children, anemia in 11 children and granulocytopenia in 4 children.The concentration of ceruloplasmin in the serum of MD children was lower than that in healthy children of the same age.The concentration of ceruloplasmin in MD children younger than 3 months was significantly lower than that in healthy children of the same age and MD children older than 3 months.The brain magnetic resonance imaging showed abnormalities in all 15 children.Twelve children showed tortuous intracranial vessels in brain magnetic resonance angiography examinations.All the 15 children had ATP7A gene pathogenic variants, including 4 missense variants(2 cases with c. 2179G>A), 3 frameshift variants, 3 nonsense variants, 3 exon deletions and 2 splice site variants.Among these children, 1 had a novel gene variant that had not been reported so far(c.2968C>T). Conclusions:MD has early onset age and diverse clinical manifestations, but also has characteristic clinical manifestations and applicable auxiliary examinations.Its diagnosis depends on genetic testing.The c. 2179G>A and exon deletions may be hot mutations in Chinese MD patients.

Objective To explore the clinical features of methylmalonic acidemia (MMA) in children admitted to the pediatric intensive care unit, to help improve our understanding of MMA. Methods The clinical data of 21 patients with MMA admitted to our PICU from December 2012 to August 2016 were analyzed. Diagnosis were confirmed by gas chromatography-mass spectrometry, GC/MS. Results twenty-four of 158 suspected cases were confirmed as having organic acidemia diseases including 21 cases of MMA, one case of propionic acidemia, one case of urea cycle disorders, and one case of glutaric acidemia. The main clinical manifestations were feeding difficulty, malnutrition (13 cases), developmental retardation (12 cases), lethargy (10 cases), tricuspid severe reflux and pulmonary hypertension (1 case), hydrocephaly (5 cases), muscular dystonia (three cases with hypertonia, and four with hypotonia), convulsion (7 cases), apnea, sobbing respiration (10 cases), chromatosis (6 cases), anemia (13 cases), edema (6 cases), thrombocytopenia (6 cases), hematuria and proteinuria (2 cases). Five cases gave up therapy before diagnosis was made. Sixteen cases received the treatment with Vitamin B12 and supplementation of L-carnitine. Seven cases gave up after treatment without effect or deterioration of condition. Eight cases were vitamin B12-responsive, and one case was vitamin B12-nonresponsive. The follow-up for a period ranging from three months to two years, among eight vitamin B12-responsive cases, 6 cases showed a favorable outcome with apparent improvement, one case had no symptom and one patient died from severe pneumonia. Vitamin B12-nonresponsive case was still alive. Conclusions The clinical manifestations of MMA are non-specific. Urine organic acid analysis is critical to early diagnosis of MMA in high-risk patients. Timely diagnosis and appropriate long-term treatment are essential to improve the prognosis of the disease.

Obgective To investigate the clinical effect of Adenine arabinoside monophosphate (Ara-A) on the treatment of infant cytomegalovirus hepatitis.Methods One hundred cases of infants with cytomegalovirus hepatitis in the Third Affiliated Hospital of Zhengzhou University from January 2012 to October 2013 were included and divided into 2 groups:Am-A group treated with Ara-A [a course of treatment lasting for 2 months included 10 mg/(kg · d) for first 2 weeks followed by 2 weeks' interval,and then resumed],and then control group was given ganciclovir [10 mg/(kg · d) for 14 days and 5 mg/(kg · d) for 1 week after 1 week's interval,for a total treatment period of 1.5 to 2.0 months].Both groups were given conventional therapy.Both before and after treatment,liver function,time of jaundice and transaminase back to normal,quantification of viral DNA returns to negative,side effects,hospitalization time and cost were also compared.Results After 2 weeks,alanine aminotramferase(ALT) in Ara-A group was significantly lower than that of the control group,and there was significant difference (P ＜0.05).After 2 months,ALT,aspartate transaminase in Ara-A group were significantly lower than those in the control group (all P ＜ 0.05).Time of transaminase back to normal [(38.5 ± 16.7) d] was significantly reduced compared with the control group [(44.3 ±22.9) d] (F =3.845,P ＜ 0.05).Time of jaundice back to normal [(27.1 ± 10.5) d],quantification of viral DNA back to negative [(39.5 ±24.0) d],hospitalization time [(22.6 ±5.8) d] and costs [(10 521.9 ±2 662.3) yuan] in Ara-A group had no significant difference compared with those of the control group (F =1.111,2.837,0.840,2.223,all P ＞ 0.05).The negative rate of viral DNA quantification in Ara-A group (80.9％) was higher than that of the control group (62.1％),and the liver injury rate (7.1％) was lower than that of the control group (15.5％),and the difference was statistically significant (x2 =9.137,11.514,all P ＜ 0.05).Condusion Ara-A is safe and effective for infant cytomegalovirus hepatitis and it is suitable for the clinical practice.

OBJECTIVE: To summarize the diagnostic and therapeutic experience of primary cricopharyngeal achalasia and introduce new operandi modus. METHOD: Report the two cases we treated in 2008 and integrate published literature, and approach its diagnostic and therapeutic experience and make use of new operandi modus. RESULT: The diagnosis of primary cricopharyngeal achalasia is difficult, and we must apply exclusive diagnosis according to the examinations of fibrolaryngoscopy, esophagoscopy and barium meal et al. CONCLUSION Surgical treatment is the best option. Partial resection of cricopharyngeal muscle and upper esophageal ring-shaped muscle is superior to simple cricopharyngeal myotomy.
Aged ; Esophageal Achalasia ; diagnosis ; surgery ; Female ; Humans ; Middle Aged ; Pharyngeal Diseases ; diagnosis ; surgery ; Pharyngeal Muscles ; physiopathology