Clinical characteristics and molecular genetic analysis of ten cases of ornithine carbamoyltransferase deficiency in southeastern China.

BACKGROUND: This study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD. METHODS: A retrospective analysis was performed on the clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 at Quanzhou Maternity and Children's Hospital of Fujian Province in China. RESULTS: Five boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. In contrast, five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all presenting with hepatic impairment, and four with hepatic failure.Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T > A(p.M56K). Of seven patients who died, five had early-onset disease despite active treatment. Three patients survived, and two of them underwent liver transplantation. CONCLUSIONS: The clinical manifestations of OTCD lack specificity. However, elevated blood ammonia levels serve as a crucial diagnostic clue for OTCD. Genetic testing aids in more accurate diagnosis and prognosis assessment by clinicians. In addition, we identified two novel pathogenic variants and expand the mutational spectrum of the gene OTC, which may contribute to a better understanding of the clinical and genetic characteristics of OTCD patients.

Chinese familial central precocious puberty with hyperuricemia due to recurrent DLK1 mutation: Case report and review of the literature.

BACKGROUND: Central precocious puberty (CPP) is a precocious puberty due to premature activation of the hypothalamic-pituitary-gonadal axis (HPG). MKRN3 defects are well-known causes of CPP, while DLK1 mutations were recently identified in a few patients with CPP. METHODS: The study was approved by the Institutional Review and the scientific committee of the hospital. The clinical data were collected. Whole-exome sequencing (WES) was performed to detect causative variants. Key words 'DLK1', 'MKRN3', and "central precocious puberty" were used for literature search in PubMed, Google Scholar, HGMD, and OMIM databases. RESULTS: The patient, a male, whose puberty began before age nine, had significant metabolic abnormalities including overweight, hyperlipidemia, and hyperuricemia. WES detected a recurrent frame-shift mutation, NM_003836.5:c.479delC(p.P160fs*50) in DLK1 in the patient and his father. CONCLUSION: The familial DLK1-CPP was identified in China for the first time, which supported that short stature is predicted in patients with CPP without GnRHa treatment. Therefore, we recommend that children with DLK1-CPP should be treated as early as possible to improve adult height. The patient in this study had persistent hyperuricemia, further suggests that this antiadipogenic factor represents a link between reproduction and metabolism.

Clinical effect of methimazole combined with selenium in the treatment of toxic diffuse goiter in children.

BACKGROUND: The incidence of toxic diffuse goiter (Graves' disease) is higher in adolescents and preschool-aged children, with an upward trend. The incidence at 6-13 years of age is approximately 11.0%, and the incidences in men and women are 7.8% and 14.3%, respectively. AIM: To explore the clinical effect of methimazole combined with selenium in the treatment of toxic diffuse goiter (Graves' disease) in children and its effect on serum anti-thyroglobulin antibody (TRAb) and anti-thyroid peroxidase antibody (TPOAb). METHODS: A total of 103 children with Graves' disease treated in our hospital from January 2018 to June 2021 were divided into a traditional group and a combined group (15-20 mg methimazole orally given to children) and a combined group (50 µg selenium added on the basis of traditional treatment) according to different treatment methods to explore the therapeutic effects of the two methods and to observe the changes in thyroid volume and serum TRAb, TPOAb, free thyroxine (FT4) and inflammatory factor levels before and after treatment. The time taken for FT4 to return to normal was compared between the two groups. RESULTS: Treatment was significantly more effective in the combined group than in the traditional group (P < 0.05). The thyroid volumes of the children in the two groups was measured before and after treatment. Thyroid volume decreased significantly after treatment in both groups, and the thyroid volume was significantly lower in the combined group than in the traditional group (P < 0.05). The serum levels of interleukin-6 (IL-6), IL-8, TRAb, TPOAb and FT4 in the two groups were detected before and after treatment. The levels of IL-6, IL-8, TRAb, TPOAb and FT4 were significantly lower in the combined group than in the traditional group (P < 0.05). Follow-up of the children in the two groups showed that compared with the traditional group, it took less time for children in the combined group to return to the normal level (P < 0.05). CONCLUSION: Methimazole combined with selenium can effectively treat Graves' disease in children, reduce the expression of TRAb, TPOAb, FT4 and inflammatory factors, and improve the curative effect. Thus, the combined treatment warrants further clinical research.

Case report: A novel c.1842_1845dup mutation of ETFDH in two Chinese siblings with multiple acyl-CoA dehydrogenase deficiency.

This article reports the characterization of two siblings diagnosed with late-onset multiple Acyl-CoA dehydrogenase deficiency (MADD) caused by mutations in electron transfer flavoprotein(ETF)-ubiquinone oxidoreductase (ETF-QO) (ETFDH) gene. Whole exome sequencing (WES) was performed in the proband's pedigree. Clinical phenotypes of Proband 1 (acidosis, hypoglycemia, hypotonia, muscle weakness, vomiting, hypoglycemia, hepatomegaly, glutaric acidemia, and glutaric aciduria) were consistent with symptoms of MADD caused by the ETFDH mutation. However, Proband 2 presented with only a short stature. The patients (exhibiting Probands 1 and 2) showed identical elevations of C6, C8, C10, C12, and C14:1. c.1842_1845 (exon13)dup, and c.250 (exon3) G > A of the ETFDH gene were compound heterozygous variants in both patients. The novel variant c.1842_1845dup was rated as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines (ACMG). This is the first report on the c.1842_1845dup mutation of the ETFDH gene in patients with late-onset MADD, and the data described herein may help expand the mutation spectrum of ETFDH.

Clinical, biochemical, and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report.

BACKGROUND: Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in defects in several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions. CASE PRESENTATION: In this paper, we report a Chinese Han pedigree with HLCS deficiency diagnosed by using next-generation sequencing and validated with Sanger sequencing of the HLCS and BTD genes. The Chinese proband carries the common missense mutation c.1522C > T (p.Arg508Trp) in exon 9 of the HLCS gene, which generates an increased Km value for biotin. A novel frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15) in exon 6 of the HLCS gene is predicted to be deleterious through PROVEAN and MutationTaster. A novel heterozygous mutation, c.638_642delAACAC (p.His213Profs*4), in the BTD gene is also identified. CONCLUSIONS: The Chinese proband carries the reported Arg508Trp variant, the novel 2-bp frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15), which expands the mutational spectrum of the HLCS gene, and the novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4), which expands the mutational spectrum of the BTD gene. Furthermore, reversible hearing damage is rarely reported in patients with HLCS deficiency, which deserves further discussion.

[The diagnostic value of serum beta-hydroxybutyrate in diabetic ketosis or diabetic ketoacidosis].

OBJECTIVE: To determine the diagnostic value of serum beta-hydroxybutyrate (betaOHB) in diabetic ketosis or diabetic ketoacidosis. METHODS: We conducted a retrospective review of clinical data, in West China Hospital from May 2011 to May 2013, of 1 209 patients with non-ketosis diabetics (DM group), 262 patients with diabetic ketosis or diabetic ketoacidosis (DK/DKA group), and 480 healthy people undergoing routine medical examinations (normal control group). Logistic regression analyses and ROC curves were performed in determining the diagnostic value of betaOHB for DK/DKA. RESULTS: The level of serum betaOHB was much higher in the DK/DKA patients than that of the participants in the DM group and normal control group (P < 0.01). The serum betaOHB turned negative earlier than urine ketone (P < 0.01) in the DK/DKA patients. The logistic regression analysis indicated that betaOHB was one of the independent risk factors for DK/DKA. The betaOHB had an area under of 0.975 in ROC curve, with 1 mmol/L [sensitivity (Sen.) 85.1%, specificity (Spe.) 95. 3%, positive predictive value (PV+) 80.36%, negative predictive value (PV-) 96.89%] as a diagnostic point for DK/DKA and 0.66 mmol/L (Sen. 95%, Spe. 89.2%, PV+ 66.41%, PV- 99.9%) as a screening point. CONCLUSION: Diabetic patients with a level or higher than 1 mmol/L serum betaOHB can accurately predict DK/DKA. Patients with a level or lower than 0.66 mmol/L serum betaOHB are unlikely to have DK/DKA.

[Procalcitonin as a predictor of trauma severity and post-traumatic sepsis in children].

OBJECTIVE: To determine the association of procalcitonin (PCT) with trauma severity and post traumatic sepsis in children. METHODS: The blood samples of 30 children with acute trauma in a Pediatric unit were collected for four consecutive days. The levels of PCT, IL-6, CRP and WBC were measured. The pediatric trauma score (PTS), length of stay in hospital, incidence of sepsis and clinical outcomes of the children were recorded. The value of PCT for predicting prognosis of children with trauma was compared with other inflammatory markers. RESULTS: Plasma PCT levels increased significantly in the patients in our study. Sepsis occurred in 23.33% of the patients. The patients with sepsis had higher levels of PCT than those with and without systemic inflammatory response syndrome (SIRS) and the healthy controls (P < 0.05). The peak level of PCT emerged on day 2 after trauma. The plasma PCT levels were positively correlated with trauma severity. The level of PCT on day 2 was an independent predictor for post-trauma sepsis and SIRS. CONCLUSION: Plasma PCT levels increase markedly in post trauma children. Plasma PCT of day 2 after trauma is an independent predictor of post-traumatic sepsis and SIRS complications. There is a significant correlation between the severity of injury and plasma PCT.