Allan-Herndon-Dudley syndrome in a female patient and related mechanisms.

peer reviewedAllan-Herndon-Dudley syndrome (AHDS) is characterized by neuropsychomotor developmental delay/intellectual disability, neurological impairment with a movement disorder, and an abnormal thyroid hormone profile. This disease is an X-linked disorder that mainly affects men. We described a female patient with a de novo variant in the SLC16A2 gene, a milder AHDS phenotype, and a skewed X chromosome inactivation profile. We discuss the mechanisms associated with the expression of the phenotypic characteristics in female patients, including SLC16A2 gene variants and cytogenomic alterations, as well as preferential inactivation of the normal X chromosome

Intraventricular hemorrhage in preterm infants: risk factors and neurodevelopmental outcomes

Introduction: Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is the most common form of intracranial hemorrhage in preterm infants. We evaluated risk factors for GMH-IVH in preterm infants born before 32 weeks of gestational age. Secondary outcomes included the characterization of neurodevelopmental (ND) prognosis at 24-36 months of corrected age. Methods: We included infants admitted to our Neonatal Intensive Care Unit between May 2011 and January 2017. A total of 161 infants were enrolled, divided into the GMH-IVH group (n = 40) and control group (n = 121). A secondary cohort included the follow-up group (n = 124) at 24-36 months of corrected age. The association of GMH-IVH with risk factors and ND outcomes was investigated. Results: The incidence of GMH-IVH was 24.8%. Significant risk factors for GMH-IVH were exposure to any resuscitation in the Delivery Room (adjusted odds ratio [aOR]: 34.1; 95% confidence interval [CI] 1.8-657.5) and a low Apgar score at 5 minutes of life (aOR: 0.4; 95% CI: 0.2-0.9). The incidence of retinopathy of prematurity was significantly higher in the grade I GMH-IVH (p < 0.001) group. Gross motor and locomotion dysfunction were significantly more frequent in the GMH-IVH group (24.1% vs. 4.4%; p = 0.004) as was auditory and language dysfunction (24.1% vs. 7.8%; p = 0.040). GMH-IVH was independently associated with visual impairment (aOR: 21.6; 95% CI: 3.2-145.0).  Conclusions: Lower Apgar score at 5 minutes of life and any resuscitation were independent risk factors for GMH-IVH. GMH-IVH was associated with higher ND morbidity. ND prognosis of grade II GMH-IVH was comparable to grade III GMH-IVH

Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant

Research reportFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226392/Introduction: Combined oxidative phosphorylation deficiency 20 (COXPD20) is a mitochondrial respiratory chain complex (RC) disorder, caused by disease-causing variants in the VARS2 gene, which encodes a mitochondrial aminoacyl-tRNA synthetase. Here we describe a patient with fatal mitochondrial encephalopathy caused by a homozygous VARS2 gene missense variant. Case Report: We report the case of a girl, the first child of non-consanguineous and healthy parents, born from an uneventful term pregnancy, who presented, in the neonatal period, major hypotonia and microcephaly. At 4 months of age she showed poor eye contact, nystagmus, global psychomotor development delay and failure to thrive, without dysmorphic features. Focal seizures started at 24 months which evolved to a severe epileptic encephalopathy and finally to super refractory status epilepticus, leading to her death at 28 months of age. Etiologic investigation encompassing metabolic and genetic causes failed to disclose a diagnosis. Post-mortem exome sequencing allowed the identification of a pathogenic variant in VARS2 gene in the homozygous state (c.1100C > T, p.Thr367Ile) in the patient, inherited from her heterozygous parents, leading to the diagnosis of COXPD2. Conclusion: To the best of our knowledge, this is the fifth case described in the literature of a child with disease-causing variant in VARS2. With this report we expand the knowledge about the phenotype associated with this very rare mitochondrial defect, further emphasizing the use of exome sequencing as a very powerful diagnostic tool.info:eu-repo/semantics/publishedVersio

Frequência de Mutações de Resistência aos ARVs em novos casos de infeção por VIH-1, diagnosticados em Portugal no ano 2018

Introdução: A avaliação da presença de mutações que confiram resistência aos fármacos usados no tratamento da infeção por VIH-1, faz parte da avaliação laboratorial efetuada no quadro de um diagnóstico de novo, e a monitorização da sua prevalência é preconizada internacionalmente. Objetivos: Avaliar a frequência de mutações de resistência (MR) entre doentes com diagnóstico estabelecido em 2018 e identificar determinantes para a sua ocorrência.N/