Objective To investigate the clinical, biochemical and genetic features of a Chinese boy with holocarboxylase synthetase deficiency (HCSD). Methods The clinical and genetic data of a rare case of HCSD were retrospectively analyzed. Results After birth, the boy showed development delay. At 3 months old, the boy was started with rehabilitation. Tandem mass spectrum and gas chromatography analysis was carried in the 5th month after birth because of the recurrent upper respiratory tract infection and elevated level of C5-OH in the blood and decreased level of C0,and elevated level of 3-OH-propionic, pyruvic acid, methylcrotonylglycine in the urine were in accordance with the HCSD. Genetic analysis found compound heterozygous mutations of c.1648G>A and c.1544G>A in gene, of which the latter one is novel. After the treatment of biotin (20 mg/d) and L-Carnitine, the condition of this boy was gradually improved. Conclutions HCSD is characterized with slow onset and inconspicuous manifestations. The confirmed diagnosis can be built with MS/MS, GC/MS analysis and gene mutation analysis. The effect of early biotin treatment is satisfactory. In this study,we carried out clinical and genetic diagnosis,which lays a solid foundation for prenatal diagnosis and early treatment.

Objective To explore the clinical features, diagnosis, and treatment of congenital disorder of glycosylation type 1a (CDG-Ⅰa), a rare inherited metabolic disease. Methods The clinical data and the gene detection results of one case of CDG-Ia which was discovered because the case had encephalopathy and hepatopathy were retrospectively analyzed. The related literatures were reviewed. Results Male infant suffered with face and trunk rash, motor development retardation, malnutrition, cheek fat plump, low limbs muscle tone, and bilateral crater nipple at 3 months old. Abnormal liver function and mild renal impairment were found after examination. The development quotient was low. Head MRI showed that bilateral frontal and temporal sulcus widening, and cerebellar atrophy. Urinary organic acids, amino acids, carnitine, and biotin activities were normal. Gene sequencing revealed that there were two heterozygous mutations, c.430T>C (p.F144L) and c.713G>C (p.R238P), in the PMM2 gene. The diagnosis of CDG-Ⅰa was confirmed. Both of the infant's parents were healthy, and each of them carries a pathogenic mutation. The infant had an elder brother who had mental disorder and died for liver and kidney function damage and hydronephrosis at 8 months old. Conclusion CDG-Ⅰa is an autosomal recessive disease. For infants with unexplained multiple organ damage, especially combined with intelligent and motor development retardations, strabismus, nipple retraction, and cerebellar atrophy, the possibility of CDG-Ⅰa should be considered. Gene detection of PMM2 can help the diagnosis.

Intellectual disability is a common disease in children′s nervous system, which seriously endangers children′s physical and mental health.The etiology of the intellectual disability is complex, and many genetic and environmental factors are involved in the process of it.Inherited metabolic disorders are an important cause of the disease.With the improvement of diagnosis and treatment level, the clinical outcome of children with inherited metabolic disorders can be greatly improved after early diagnosis and treatment.Therefore, it is of great significance for guiding the treatment, prognosis and reproduction of patients to identify the inherited metabolic disorders that lead to intellectual disability in time and as early as possible.Now, the known inherited metabolic disorders that lead to intellectual disability, such as phenylketonuria, mitochondrial disease, urea circulatory disorder, creatine deficiency syndrome, and lysosomal storage syndrome, etc, are summarized, which are helpful to understand its clinical characteristics and improve the clinical recognition.

Objective:To analyze the neurodevelopmental characteristics of the children with methylmalonic acidemia and investigate its possible influencing factors.Methods:The clinical questionnaire was used to collect clinical data of children with methylmalonic acidemia at the First Affiliated Hospital of Henan University of Chinese Medicine from February 2016 to February 2018, and Gesell development scal was used to evaluate the neurodevelopment.Results:Among the 86 patients, 45 cases were boys and 41 cases were girls.They were 2.4 to 62.5 months, and the minimum age was 8.3 months.Thirty-three cases were detected by neonatal screening, 53 cases were diagnosed after onset.The energy zone in this children were mild to severe developmental defects.Twenty-eight cases were 0 to 6 months old, and fine exercise, the large exercise and adaptability developmental defects were significant of them; 24 cases were >6 to 12 months old, and the language, adaptability and personal-social developmental defects were significant of them; 23 cases were >12 to 36 months old, and the language, adaptability and large movements developmental defects were significant of them; 11 cases aged >36 to 72 months had significant developmental defects in language, personal-social contact and adaptability.The developmental quotients of fine movements, big movements, adaptability, personal-social and language of the children diagnosed by newborn screening were much better than those diagnosed after onset in each energy zone(all P<0.05). Conclusions:Although the treatment is actively regulated, most children with methylmalonic acidemia still have neurodevelopmental abnormalities with varying degrees of severity.The children before the age of 6 months have significant defects in motor movement and adaptability development.The patients after the age of 6 months usually have language, adaptability and social contact defects.Newborn screening is important and nervous system damage is milder in the children diagnosed by newborn screening.

Objective Mitochondrial DNA depletion syndrome is a rare autosomal recessive disorder characterized by complex genetic and clinical manifestations.This study aimed to investigate the clinical and laboratory features of a boy with mitochondrial encephalomyopathy caused by SUCLG1 mutation.Methods The clinical data and genetic test of a patient with mitochondrial DNA depletion syndrome were retrospectively analyzed.Result The proband presented with limb weakness at the 4th month after birth,and presented dystrophic appearance,muscular hypotonia,psychomotor retardation,failure to thrive,hearing impairment,scoliosis,thoracocyllosis and facial features at 9 months old.Laboratory tests showed blood lactic acid and pymvate increased,liver damage and abnormal myocardial enzymes.Plasma camitine ester profiling showed that amino acids decreased and C4-dicarboxylic-carnitine increased.Urinary organic acid analysis showed increased concentration of methylmalonic acid and its metabolites indicating methyl malonic aciduria.MRI showed bilateral T2 hyperintensities in bilateral caudate nuelei and lenticular and brain atrophy-like changes.Brainstem auditory evoked potential showed severe hearing loss.His development quotient was 35.Genetic sequencing of MUT,,MMAA,MMAB and other classic mitochondrial disease related genes of the proband revealed no mutation.Two heterozygous mutations,c.961C＞G and c.713T＞C,inherited from the phenotype of normal parents were detected in his SUCLG1 gene.The copy number of mitochondrial DNA was 244/cell in peripheral blood leukocytes,equivalent to 68.4％ of that in normal control.Conclusion In this study,an infant with muscular hypotonia,psychomotor retardation,deafness and slightly increased urine methyl malonic acid was diagnosed by genetic test.For patients with unexplained hypotonia,mental retardation,abnormal movements,hearing disorder together with increased blood pyruvic acid and lactic acid,mild methylmalonic acidemia and abnormal acylcarnitine,mitochondrial DNA depletion syndrome should be considered.Gene analysis is important for diagnosis and prenatal diagnosis of the next pregnancy.

Objective:To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency.Methods:This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively.Results:The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders.Conclusions:Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Acute respiratory tract infection is the most common infectious disease in children, which seriously threatens children′s health.Rapid and accurate etiological diagnosis is of great significance for the clinical treatment and control of these diseases.Pathogen nucleic acid test was applied and became the main method of respiratory tract infection diagnosis for its high sensitivity and specificity.To regulate the application of pathogen nucleic acid amplification test in respiratory tract infection in children, improve the diagnosis level, expert consensus on nucleic acid amplification test of respiratory pathogens in children was prepared to guide the application and promote pathogens diagnosis ability.

Objective:This study aimed to provide basic data for the prevention, diagnosis and treatment of pediatric viral myocarditis (VMC) in China through analyzing the epidemic characteristics and disease burden of pediatric inpatients with VMC from 2016 to 2021.Methods:We performed a descriptive statistical analysis to the age, genders, seasons, regions and hospitalization cost and days of pediatric VMC inpatients and the death. All of the information was obtained from 27 Children′s hospitals or Maternal and Child Health hospitals of 23 provinces of China from 2016 to 2021.Results:A total of 7 647 599 cases including 1 646 VMC inpatients were admitted into our study. The annual numbers of hospitalizations were 173, 227, 313, 301, 295 and 337, with the hospitalized constituent ratios being 14.9/100 000, 17.9/100 000, 23.0/100 000, 20.5/100 000, 26.5/100 000 and 26.4/100 000 from 2016 to 2021. In recent 6 years, the proportion of VMC hospitalizations had increased yearly ( P<0.001), and had associated with the onset age ( P<0.001). Aged 12-≤18 years owned the highest hospitalized constituent ratio. The Northeast of China owned the largest number of VMC inpatients, and the East second to it. Among the 1 646 VMC children, there were 68 deaths, with the hospitalized case fatality rate of 4.13%. There were no significant differences between genders, age, seasons, years and fatality rate of VMC inpatients. For the diseases burden, the median of hospitalization days of all VMC inpatients was 10 days (IQR 6, 21), and the median of hospitalization cost was 1 1 842.3 RMB (IQR 6 969.22, 19 714.78). The median of hospitalization days of deceased VMC children was only 1 day (IQR 1, 3), the median cost could be 8 874.03 RMB (IQR 5 277.94, 5 6 151.59). Conclusions:In this study, we found that proportion of hospitalization of VMC children increased year by year, adolescence might be a risk factor of VMC. The fatality of VMC inpatients could be up to 4.13%, and the death led to a huge economic burden of society, family and individuals.