Treatment and management for children with urea cycle disorder in chronic stage. / å°¿ç´ å¾ªçŽ¯éšœç¢æ‚£å„¿æ ¢æ€§æœŸæ²»ç–—å’Œç®¡ç†.

Urea cycle disorder (UCD) is a group of inherited metabolic diseases with high disability or fatality rate, which need long-term drug treatment and diet management. Except those with Citrin deficiency or liver transplantation, all pediatric patients require lifelong low protein diet with safe levels of protein intake and adequate energy and lipids supply for their corresponding age; supplementing essential amino acids and protein-free milk are also needed if necessary. The drugs for long-term use include nitrogen scavengers (sodium benzoate, sodium phenylbutyrate, glycerol phenylbutyrate), urea cycle activation/substrate supplementation agents (N-carbamylglutamate, arginine, citrulline), etc. Liver transplantation is recommended for pediatric patients not responding to standard diet and drug treatment, and those with severe progressive liver disease and/or recurrent metabolic decompensations. Gene therapy, stem cell therapy, enzyme therapy and other novel technologies may offer options for treatment in UCD patients. The regular biochemical assessments like blood ammonia, liver function and plasma amino acid profile are needed, and physical growth, intellectual development, nutritional intake should be also evaluated for adjusting treatment in time.

[Analysis of clinical features, biochemical indices and genetic variants among children with Short/branched-chain acyl-CoA dehydrogenase deficiency detected by neonatal screening].

OBJECTIVE: To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. METHODS: A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. RESULTS: Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. CONCLUSION: SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.

Effect of hot water extracts of Arthrospira maxima (spirulina) against respiratory syncytial virus.

BACKGROUND: Spirulina (Arthrospira maxima) hot water extracts such as calcium spirulan (Ca-SP) have demonstrated antiviral effects against herpes simplex virus (HSV), human immunodeficiency virus-1 (HIV-1), and influenza virus infections. There is no prior evidence suggesting the anti-viral activity of the spirulina hot water extract against respiratory syncytial virus (RSV). PURPOSE: There are currently no effective antivirals available to treat RSV infection. Therefore, the development of safe and novel anti-RSV drugs is urgent and necessary. The aim of this work was to demonstrate the anti-RSV activity of spirulina hot water extracts and determine the potential mechanism of action. METHODS: Cytotoxicity and anti-RSV activity of spirulina hot water extracts were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutralization assays, respectively. Potential mechanisms and components were assessed using time of addition, attachment, internalization, pull-down assays, and composition analysis. RESULTS: The polysaccharide-enriched high-molecular weight fraction (>100 kDa, SHD1) had a high total sugar content, with rhamnose accounting for approximately 60 mol% of total monosaccharides. The main glycosyl linkages included 3-, 4-, and 2,3-rhamnopyranosyl linkages. All spirulina hot water extracts showed no toxicity toward human epithelial type 2 (HEp-2) cells but demonstrated anti-RSV activity. The SHD1 had a half maximal effective concentration (EC50) of 0.0915 mg/ml and a selective index (SI) of >261.5 against RSV. SHD1 significantly reduced viral yield in a dose-dependent manner during the RSV attachment stage. SHD1 disrupted RSV internalization and inhibited RSV attachment (G) protein binding to heparan sulfate receptors on the host cell surface, thus preventing RSV attachment and entry. CONCLUSION: SHD1 serves as an effective candidate for novel drug development against RSV infection.

Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients.

To investigate the incidence rate, clinical and gene mutation characteristics of multiple acyl-CoA dehydrogenase deficiency (MADD) in newborns in Zhejiang province. A total of 3 896 789 newborns were screened for MADD using tandem mass spectrometry in Zhejiang Neonatal Screening Center during January 2009 and December 2020. Patients of MADD were confirmed by urine organic acid and electron transferring flavoprotein (or electron transferring flavoprotein dehydrogenase () gene detection. MADD patients were given diet and life management, supplemented with L-carnitine, riboflavin and coenzyme Q 10 treatment, and their growth and intellectual development were evaluated during the followed up.Thirteen patients with MADD were diagnosed, with an incidence of 1/299 753. One patient was type Ⅱ, and the rest were type Ⅲ. Patients were followed up for 1 case died, 4 cases had acute metabolic disorders with hypoglycemia as the main manifestation due to infection, 1 case had hypotonia, and the rest 7 cases developed well. Patients had raised levels of C4-C18:1 acylcarnitines in the initial screening. Thirteen children were genetically tested, 1 case with compound heterozygous mutation in the gene, 1 case with homozygous mutation in the gene, 1 case with compound heterozygous mutation in the gene, 8 cases with compound heterozygous mutation and 1 case with homozygous mutation in the gene, 1 case that only 1 locus of gene was detected. The c.250G>A was the hotspot mutation in this study.The clinical manifestations of MADD are highly heterogeneous. The neonatal-onset form is serious, and late onset form usually has no obvious clinical symptoms. C4-C18:1 acylcarnitines usually increased in the initial screening, and the hotspot gene mutation is c.250G>A.

Diagnosis, treatment and outcome of glutaric aciduria type I in Zhejiang Province, China.

BACKGROUND: Glutaric aciduria type I (GA I; MIM 231670) is a rare autosomal recessive disorder resulting from glutaryl-CoA dehydrogenase deficiency. This article reports our experience in the diagnosis, treatment and outcome of GA I patients in Zhejiang Province, China. MATERIAL/METHODS: A total of 129,415 newborns (accounting for approximately one-tenth of the annual births in Zhejiang Province) and 9640 high-risk infants were screened for inborn errors of metabolism in the Neonatal Screening Center of Zhejiang Province during a 3-year period. Tandem mass spectrometry and gas chromatography-mass spectrometry were used for diagnosis of the patients. Dietary modification, carnitine supplementation and aggressive treatment of intercurrent illnesses were adapted for GA I patients. RESULTS: Three infants were diagnosed with GA I by high-risk screening (detection rate: 1/3,213) and 2 were diagnosed by newborn screening (incidence: 1/64,708). Four patients (3 by high-risk screening and 1 by neonatal screening) undergoing MRI examination showed remarkable changes on T2-weighted image. Four patients accepted timely treatment, and in the patient diagnosed by neonatal screening, treatment was delayed until hypotonia appeared 3 months later. Neuropsychological assessment showed mental and motor retardation in 3 patients after treatment, including the patient diagnosed by neonatal screening. CONCLUSIONS: Individualized timely treatment and close monitoring of GA I patients needs to be optimized in China. Appropriate communication with parents may help to achieve successful management of GA I patients.

[Screening for neonatal inborn errors of metabolism by electrospray ionization-tandem mass spectrometry and follow-up].

OBJECTIVE: To determine the impact of expanded newborn screening using tandem mass spectrometry (MS/MS) on the overall detection rate of inborn errors of metabolism in Zhejiang province and to assess the outcome of the patients who were diagnosed. METHOD: Blood spots were collected between days 3 and 6 of life from the newborns. All samples were subjected to MS/MS analysis using Waters Quattro API. Confirmation tests included amino acid analysis, urinary organic acids by GC-MS, routine blood analysis, biochemistry, blood gas analysis, blood glucose and ammonia tests, blood homocysteine, lactate and pyruvate tests, urine acetone tests, biotin and biotin enzyme profile and DNA analysis. Standard treatment protocol was given to the patients. Protein restricted diet, special powdered formula and medicines recommended for the patients with amino acidemias. Protein restricted diet and L-carnitine, folic acid and Vitamin B12 supplementation were given for the patients with organic acidemia. L-carnitine was given to the patients with primary carnitine deficiency. The overall epidemiology, prognosis, follow-up of the screening program were also investigated in the neonates. RESULT: A total of 129 415 neonates were investigated for 26 inborn errors of metabolism during the period. Twenty-three newborns were confirmed as having inborn errors of metabolism, including 13 with amino acidemias, 6 with organic acidemias and 4 with fatty acid oxidation disorders. The prevalence was 1:5626. Positive predictive value was 2.10%, specificity was 99.72% and sensitivity 100%. Seventeen children remain asymptomatic during the follow-up. Five patients had motor and mental developmental delay. One patient presented metabolic disorders during the follow-up. No death occurred in this series of patients. CONCLUSION: This strategy represents a valuable preventive medicine approach by enabling diagnosis and treatment before the onset of symptoms.

The survey of serum retinol of the children aged 0~4 years in Zhejiang Province, China.

BACKGROUND: Vitamin A can have a positive impact on growth and development of children, but vitamin A deficiency (VAD) was found to be a public health problem in Zhejiang Province, China in 1998. There have been no studies on this topic in Zhejiang Province recently. This study was designed to evaluate the serum retinol levels of children aged 0~4 years in Zhejiang Province, southeast China. This epidemiological data will help design supplementation strategies for vitamin A in high-risk groups and improve their vitamin A status. METHODS: Children were randomly recruited for this study using a stratified sampling method. A blood sample was collected from each child. Assessment included C-reactive protein (CRP), serum retinol was measured with HPLC and a questionnaire completed providing for family information and nutritional status. Logistic regression analysis was used to evaluate the risk factors for VAD in children. RESULTS: A group of 357 subjects aged 1 day to 4 years were recruited. The mean plasma retinol concentration was 1.653 (sd 0.47) mumol/L. There were 3.08% (11/357) of children affected with VAD, and 7.28% (26/357) of children had low vitamin A status, but none of the children showed any clinical symptoms of VAD. There was no significant difference in the levels of plasma retinol and the incidence rate of VAD between male and female children. Multivariate logistic regression analysis showed that living in urban region, having parents with good education and taking vitamin A capsule regularly prevented children from VAD, whereas being young (less than 2 years old) was a risk factor. CONCLUSION: Low vitamin A status remains a nutritional problem in Zhejiang Province. The high-risk group in this study were young, dwelled in rural regions, had parents with poor education and did not take a regular vitamin A containing supplement.