Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil.

Biotinidase deficiency is an autosomal recessive inherited metabolic disorder caused by mutations in the BTD gene. Clinical manifestations can be treated and effectively prevented with pharmacological doses of biotin. Nine novel mutations in BTD are reported in 14 children diagnosed by the newborn screening program in Minas Gerais, Brazil, from June 2013 to December 2017. Serum BTD enzyme activity was determined for all cases and some parents. Two of the mutations are deletions and seven missense mutations located in the exonic region of the BTD gene, mostly in exon 4. Two newborns were profoundly biotinidase-deficient (one homozygous p.A534V [c.1601C > T] and another, double heterozygous for a novel mutation p.R211S [c.631C > A] co-inherited with an already described mutation p.T532 M [c.1595C > T]). Two mutations were associated with a partial deficiency of biotinidase (p.F361 V [c.1081 T > G] in two homozygous children, and p.S311 T [c.932G > C] in a compound heterozygous child who co-inherited a known severe mutation p.Y438X [c.1314 T > A]). The remaining five mutations were found in compound heterozygous children. Hence, a definitive conclusion about the degree of biotinidase deficiency is not possible yet. These results emphasize the importance of sequencing the BTD gene as an important tool to gain a better understanding of the correlation between biochemical phenotype and genotype.

Tracking the turnover of SARS-CoV-2 VOCs Gamma to Delta in a Brazilian state (Minas Gerais) with a high-vaccination status.

The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.

High Incidence of Biotinidase Deficiency from a Pilot Newborn Screening Study in Minas Gerais, Brazil.

OBJECTIVE: To assess the incidence of biotinidase deficiency among newborns and their clinical outcome up to one year of age in a large pilot screening study in Minas Gerais, Brazil. METHODS: A prospective cohort study was conducted from September 2007 to June 2008 with heel-prick blood samples collected on filter paper for the purpose of newborn screening. A qualitative colorimetric test was used as the primary screening method. Colorimetric-positive cases were further tested with a serum confirmatory assay. Gene sequencing was performed for eight children suspected with biotinidase deficiency and for some of their parents. Positive cases were daily supplemented with oral biotin and were followed up for approximately six years. RESULTS: Out of 182,891 newborns screened, 129 were suspected of having biotinidase deficiency. Partial deficiency was confirmed in seven children (one was homozygous for p.D543E) and profound deficiency in one child (homozygous p.H485Q). Thus the incidence was one in 22,861 live births (95% confidence interval 1:13,503 to 1:74,454) for profound and partial biotinidase deficiency combined. Two novel mutations were detected: p.A281V and p.E177K. In silico analysis and estimation of the enzyme activity in the children and their parents showed that p.A281V is pathogenic and p.E177K behaves like p.D444H. CONCLUSION: The incidence of biotinidase deficiency in newborn screening in Minas Gerais was higher than several international studies. The sample size should be larger for final conclusions. Oral daily biotin apparently precluded clinical symptoms, but it may have been unnecessary in some newborns.

Incidence of cervical intraepithelial neoplasia in a cohort of HIV-infected women.

OBJECTIVE: To assess cervical intraepithelial neoplasia (CIN) incidence in HIV-positive women and the risk factors for these lesions. METHODS: A retrospective and longitudinal cohort study was conducted from June 13, 1997, to December 18, 2009. At the first visit, the 348 participants had a normal cytologic finding but a negative Schiller test result, or an abnormal cytologic finding but no histologic diagnosis of CIN. Infection with HPV was detected by polymerase chain reaction. The main outcome measure was CIN incidence. RESULTS: During a mean follow-up of 40 months, 47 women (13.5%) developed CIN, for an incidence of 4.1 cases per 100 person-years of follow-up. The HPV prevalence was 68.1%, 42 women (89.4%) developed CIN 1, and no invasive cervical cancers were identified. On multivariate analysis, women younger than 19 years at first sexual intercourse (RR, 2.6; 95% CI, 1.24-5.35) and women who had never used antiretrovirals or used them only during pregnancy (RR, 2.3; 95% CI, 1.31-4.19) were at higher risk for CIN. CONCLUSION: The CIN incidence was low despite the high HPV prevalence. Being younger than 19 years at first sexual intercourse and not using antiretroviral medications were found to be the main risk factors for CIN.