- Developmental outcomes and prevalence of SLC2A1 variants in young infants with hypoglycorrhachia. [Journal Article]
- BDBrain Dev 2019 Jul 17
- CONCLUSIONS: Hypoglycorrhachia may be a potential biomarker for neurodevelopmental delay instead of for GLUT1DS in neurologically asymptomatic young infants.
- Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families. [Case Reports]
- JPJ Pediatr Endocrinol Metab 2019 Jul 04
- Nephrogenic diabetes insipidus (NDI) is a rare disorder of the renal collecting tubules, characterized by an inability to concentrate urine due to an impaired response to arginine vasopressin (AVP), …
Nephrogenic diabetes insipidus (NDI) is a rare disorder of the renal collecting tubules, characterized by an inability to concentrate urine due to an impaired response to arginine vasopressin (AVP), resulting in dilute urine and polyuria. Causes of NDI are heterogeneous and diagnosing congenital NDI (cNDI) in young infants is clinically challenging, as typical symptoms are often unappreciated or inconspicuous. Instead, young infants may present with non-specific signs such as vomiting, poor feeding, failure to thrive, unexplained fevers, irritability, constipation or diarrhea. We report a 37-day-old infant who presented with polyuria and severe hypernatremic dehydration that was unresponsive to vasopressin. The patient was treated with amiloride, indomethacin and hydrochlorothiazide. Genetic analysis revealed a novel contiguous deletion involving the entire AVPR2 gene and the last exon of the adjacent ARHGAP4 gene. A study of the family confirmed the carrier status in the mother. This case illustrates the importance of molecular testing in confirming the diagnosis in the index patient, as well as in identifying asymptomatic at-risk female carriers so that appropriate genetic counselling can be given for reproductive planning. All pediatric patients with suspected cNDI should undergo genetic analysis for a definitive diagnosis.
- Expanded Prenatal Genetic and Newborn Screening: One Family's Wild Ride. [Journal Article]
- JPJ Pediatr Health Care 2019 Jun 24
- The exponential rate at which genetic testing has been integrated into routine and high-risk obstetric care has been exciting to watch. With this technical explosion, however, the knowledge surroundi…
The exponential rate at which genetic testing has been integrated into routine and high-risk obstetric care has been exciting to watch. With this technical explosion, however, the knowledge surrounding the benefits and limitations of prenatal genetic and newborn screening can be overlooked by both parents and providers. The following case exemplifies how a couple with infertility who underwent comprehensive prenatal expanded genetic carrier screening and parental karyotype experienced the benefits and limitations of such testing. It guides the reader through diagnostic testing for an infant, born to a father with a balanced translocation, who presented with an abnormal newborn screening result for an inherited metabolic disorder of fatty acid oxidation metabolism, very-long-chain acyl-coenzyme dehydrogenase deficiency, for which the prenatal expanded carrier screening result was negative.
- GeneReviews®: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- Medium-chain acyl-coenzyme A dehydrogenase (MCAD) is one of the enzymes involved in mitochondrial fatty acid β-oxidation. Fatty acid β-oxidation fuels hepatic ketogenesis, which provides a major sour…
Medium-chain acyl-coenzyme A dehydrogenase (MCAD) is one of the enzymes involved in mitochondrial fatty acid β-oxidation. Fatty acid β-oxidation fuels hepatic ketogenesis, which provides a major source of energy once hepatic glycogen stores become depleted during prolonged fasting and periods of higher energy demands. MCAD deficiency is the most common disorder of fatty acid β-oxidation and one of the most common inborn errors of metabolism. Most children are now diagnosed through newborn screening. Clinical symptoms in a previously apparently healthy child with MCAD deficiency include hypoketotic hypoglycemia and vomiting that may progress to lethargy, seizures, and coma triggered by a common illness. Hepatomegaly and liver disease are often present during an acute episode. Children appear normal at birth and – if not identified through newborn screening – typically present between age three and 24 months, although presentation even as late as adulthood is possible. The prognosis is excellent once the diagnosis is established and frequent feedings are instituted to avoid any prolonged periods of fasting.
- A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family. [Journal Article]
- MGMol Genet Genomic Med 2019 Jun 18; :e825
- CONCLUSIONS: This article reports one infant with CRYAB-related neonatal onset MFM with a novel homozygous variant in CRYAB. To our knowledge, this is the first reported case of infantile alpha-Bcrystallinopathy in the Chinese population.
- Pregnancy outcomes and mother-to-child transmission rate in HTLV-1/2 infected women attending two public hospitals in the metropolitan area of Rio de Janeiro. [Journal Article]
- PNPLoS Negl Trop Dis 2019; 13(6):e0007404
- HTLV-1/2 are transmitted sexually, by whole cell blood products and from mother-to-child (MTC), mainly through breastfeeding. HTLV-1/2 prevalence in pregnant women is high in Rio de Janeiro, however …
HTLV-1/2 are transmitted sexually, by whole cell blood products and from mother-to-child (MTC), mainly through breastfeeding. HTLV-1/2 prevalence in pregnant women is high in Rio de Janeiro, however there were no local studies addressing the rate of adverse pregnancy outcomes (APO) and MTC transmission. The aim was to study sociodemographic characteristics which may be associated to HTLV-1/2 infection and describe pregnancy outcomes and MTC transmission in HTLV-1/2-positive women. The cross-sectional study screened 1,628 pregnant women in of Rio de Janeiro (2012-2014) and found 12 asymptomatic carrier mothers (prevalence = 0.74%). Pregnancy outcome information was retrieved from medical records. Sociodemographic characteristics were similar between the positive and negative groups except for maternal age, which was higher in carrier mothers. The incidence of adverse pregnancy outcomes was similar in infected and non-infected patients (p = 0.33), however there was a high rate of premature rupture of membranes (PROM) amid infected mothers (3/12). Multilevel logistic regression found that for each additional year of age, the chance of being HTLV-1/2-positive increased 11% and that having another sexually transmitted infection (STI) increased 9 times the chance of being infected. Carrier mothers had more antenatal visits (OR = 5.26). Among the children of HTLV-1/2-positive mothers there was one fetal death, one infant death and one loss of follow-up. After two years of follow-up there was one case of MTC transmission (1/9). The mother reported breastfeeding for one month only. Knowledge about factors associated to HTLV-1/2 infection, its impact on pregnancy outcomes and the MTC transmission rate is important to guide public health policies on antenatal screening and management.
- Pneumococcal conjugate vaccines for preventing acute otitis media in children. [Journal Article]
- CDCochrane Database Syst Rev 2019 05 28; 5:CD001480
- CONCLUSIONS: Administration of the licenced CRM197-PCV7 and PHiD-CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all-cause AOM is far more uncertain. We found no evidence of a beneficial effect on all-cause AOM of administering PCVs in high-risk infants, after early infancy (i.e. in children one year and above), and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain and/or tenderness. We found no evidence of a difference in more severe local reactions, fever, or serious adverse events judged causally related to vaccination.
- Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant with Primary Immunodeficiency. [Journal Article]
- OOMICS 2019; 23(5):285-290
- Primary immunodeficiencies (PIDs) are a rare and heterogeneous group of inherited genetic disorders that are characterized by an absent or impaired immune system. In this report, we describe the use …
Primary immunodeficiencies (PIDs) are a rare and heterogeneous group of inherited genetic disorders that are characterized by an absent or impaired immune system. In this report, we describe the use of next-generation sequencing to investigate a male infant with clinical and immunological manifestations suggestive of a PID. Whole-exome sequencing of the infant along with his parents revealed a novel nucleotide variant (cytosine to adenine substitution at nucleotide position 252) in the coding region of the interleukin 2 receptor subunit gamma (IL2RG) gene. The mother was found to be a carrier. These findings are consistent with a diagnosis of X-linked severe combined immunodeficiency and represent the first such reported mutation in an Indian family. This mutation leads to an asparagine to lysine substitution (p.Asn84Lys) located in the extracellular domain of IL2RG, which is predicted to be pathogenic. Our study demonstrates the power of next-generation sequencing in identifying potential causative mutations to enable accurate clinical diagnosis, prenatal screening, and carrier female detection in PID patients. We believe that this approach, which is not a current routine in clinical practice, will become a mainstream component of individualized medicine in the near future.
- Exceptional diazoxide sensitivity in hyperinsulinaemic hypoglycaemia due to a novel HNF4A mutation. [Journal Article]
- EDEndocrinol Diabetes Metab Case Rep 2019 May 16; 2019
- Diazoxide is the first-line treatment for patients with hyperinsulinaemic hypoglycaemia (HH). Approximately 50% of patients with HH are diazoxide resistant. However, marked diazoxide sensitivity resu…
Diazoxide is the first-line treatment for patients with hyperinsulinaemic hypoglycaemia (HH). Approximately 50% of patients with HH are diazoxide resistant. However, marked diazoxide sensitivity resulting in severe hyperglycaemia is extremely uncommon and not reported previously in the context of HH due to HNF4A mutation. We report a novel observation of exceptional diazoxide sensitivity in a patient with HH due to HNF4A mutation. A female infant presented with severe persistent neonatal hypoglycaemia and was diagnosed with HH. Standard doses of diazoxide (5 mg/kg/day) resulted in marked hyperglycaemia (maximum blood glucose 21.6 mmol/L) necessitating discontinuation of diazoxide. Lower dose of diazoxide (1.5 mg/kg/day) successfully controlled HH in the proband, which was subsequently confirmed to be due to a novel HNF4A mutation. At 3 years of age, the patient maintains age appropriate fasting tolerance on low dose diazoxide (1.8 mg/kg/day) and has normal development. Diagnosis in proband's mother and maternal aunt, both of whom carried HNF4A mutation and had been diagnosed with presumed type 1 and type 2 diabetes mellitus, respectively, was revised to maturity-onset diabetes of young (MODY). Proband's 5-year-old maternal cousin, also carrier of HNF4A mutation, had transient neonatal hypoglycaemia. To conclude, patients with HH due to HNF4A mutation may require lower diazoxide than other group of patients with HH. Educating the families about the risk of marked hyperglycaemia with diazoxide is essential. The clinical phenotype of HNF4A mutation can be extremely variable. Learning points: Awareness of risk of severe hyperglycaemia with diazoxide is important and patients/families should be accordingly educated. Some patients with HH due to HNF4A mutations may require lower than standard doses of diazoxide. The clinical phenotype of HNF4A mutation can be extremely variable.
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- Serotype and molecular diversity of nasopharyngeal Streptococcus pneumoniae isolates from children before and after vaccination with the ten-valent pneumococcal conjugate vaccine (PCV10) in Ethiopia. [Journal Article]
- BIBMC Infect Dis 2019 May 10; 19(1):409
- CONCLUSIONS: This study highlights the presence of very diverse serotypes in Ethiopia where non-vaccine serotypes were predominant. Completion of the PCV10 schedule was associated with an approximately 50% reduction of vaccine-type carriage and increase of non-vaccine types. PCV13 would potentially reduce vaccine-type carriage by further 10%.