Clinical, neuroimaging, and molecular spectrum of TECPR2-associated hereditary sensory and autonomic neuropathy with intellectual disability.

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms. A cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea as core manifestations. A review of brain magnetic resonance imaging scans demonstrated a thin corpus callosum in 52%. We evaluated 17 distinct variants. Missense variants in TECPR2 are predominantly located in the N- and C-terminal regions containing ß-propeller repeats. Despite constituting nearly half of disease-associated TECPR2 variants, classifying missense variants as (likely) pathogenic according to ACMG criteria remains challenging. We estimate a pathogenic variant carrier frequency of 1/1221 in the general and 1/155 in the Jewish Ashkenazi populations. Based on clinical, neuroimaging, and genetic data, we provide recommendations for variant reporting, clinical assessment, and surveillance/treatment of individuals with TECPR2-associated disorder. This sets the stage for future prospective natural history studies.

Hemorragia subaracnoidea aneurismática en la unidad de cuidados intensivos del Hospital Luis Vernaza, Guayaquil, Ecuador / Aneurysmal subarachnoid hemorrhage in the intensive care unit of Luis Vernaza Hospital, Guayaquil, Ecuador

La hemorragia subaracnoidea puede producirse por un traumatismo cráneo encefálico o cuando el denominado aneurisma (defecto en la estructura de la pared de un vaso sanguíneo) se rompe produciendo flujo de sangre en el espacio subaracnoideo. Al respecto, se desarrolló un estudio con enfoque mixto, de tipo no experimental, descriptivo, longitudinal prospectivo; cuyo fin fue describir la hemorragia subaracnoidea aneurismática en pacientes atendidos en la unidad de cuidados intensivos del Hospital Luis Vernaza, en la ciudad de Santiago de Guayaquil, Ecuador, durante el período comprendido desde enero hasta septiembre de 2016. En el mismo participa-ron 31 pacientes con diagnóstico de hemorragia subaracnoidea aneurismática, los que fueron atendidos en ese servicio de la institución en cuestión. Entre los resultados observados se puede destacar que: 24 de los 31 involucrados eran de género femenino, más del 90% de la población de estudio tenían más de 40 años de edad; la arteria comunicante posterior resultó la más afecta-da en los pacientes estudiados (32,26 %); el 58,33% de los casos tuvo compromiso cerebral con distintos grados de afectación; el 38,71% de la población de estudio desarrolló isquemia cere-bral tardía; se estableció una relación estadísticamente significativa entre esa última complica-ción y la administración de ácido tranexámico como parte del tratamiento para evitar resangra-do, el que se presentó solamente en el 16,13% de los pacientes participantes.

Subarachnoid hemorrhage can be caused by a traumatic brain injury or when the so-called aneu-rysm (defect in the structure of the wall of a blood vessel) ruptures causing blood flow in the subarachnoid space. Based on this, it was developed a study with a mixed approach, of a non-ex-perimental, descriptive, longitudinal, prospective type in order to describe aneurysmal subara-chnoid hemorrhage in patients treated in the intensive care unit of Luis Vernaza Hospital, in the city of Santiago de Guayaquil, Ecuador, during the period from January to September 2016. The study population was constituted by 31 patients diagnosed with aneurysmal subarachnoid hemo-rrhage and treated at the service mentioned above. The results were: 24 of the 31 patients were female, more than 90% of the study population were over 40 years of age. The posterior commu-nicating artery was the most affected in the patients representing 32.26%, 58.33% of the cases had cerebral involvement with different degrees of involvement, 38.71% of the patients develo-ped late cerebral ischemia. A statistically significant relationship was established between this last complication and the administration of tranexamic acid as part of the treatment to avoid rebleeding, which occurred only in 16.13% of the participating patients.

Patient recommendations for PrEP information dissemination at family planning clinics in Atlanta, Georgia.

OBJECTIVE: Family planning (FP) clinics are an ideal setting to disseminate information about pre-exposure prophylaxis (PrEP), but little is known about women's preferences for learning about PrEP in this setting. STUDY DESIGN: We surveyed 500 women seeking care at 4 FP clinics in Atlanta. Before their provider visit, participants completed an HIV-risk screener. After, we asked participants about the HIV prevention counseling they received and how clinics could share information about PrEP. We performed descriptive analyses on demographics, HIV risk, and PrEP awareness/interest, and conducted thematic analysis on open-ended responses. RESULTS: Only 18% knew about PrEP before the study; 28% of 376 sexually-active women had≥1 risk indicator consistent with PrEP eligibility. Three hundred forty seven women (69%) shared suggestions about how clinics should share PrEP information. We categorized suggestions into 4 themes - Advertising, Conversations, Awareness and Access. Participants (n=150) suggested clinics should advertise PrEP via brochures, posters, texts, or emails; 134 wanted providers to talk to patients about PrEP. Several (n=71) suggested sharing PrEP information broadly in the community and with other clinics/providers; others (n=11) wanted improved access to PrEP services. CONCLUSIONS: Our results demonstrate overwhelming patient interest in learning more about PrEP through educational materials and directly from FP providers. Women were vocal about increasing PrEP awareness in the community, particularly among populations especially at risk for HIV (e.g., teens). These suggestions can be translated into actionable steps FP clinics can take to increase PrEP awareness and expand their reach to benefit women at risk for HIV. IMPLICATIONS: High HIV rates among women in the South make it imperative to increase awareness of PrEP among women. Atlanta women seeking care in FP clinics valued learning about PrEP and recommended feasible strategies for disseminating information about PrEP in community settings, the clinic or during patient-provider discussion.

Severe Neonatal Cholestasis as an Early Presentation of McCune-Albright Syndrome

McCune-Albright syndrome (MAS) is a rare genetic disorder characterized by café-au-lait macules, polyostotic fibrous dysplasia and multiple endocrinopathies. Liver involvement, although described, is a rare complication. We review the case of a child with MAS whose initial presentation was characterized by severe neonatal cholestasis. The case demonstrates a severe phenotype of persistent cholestasis in MAS requiring liver transplantation. This phenotype has been previously considered to be a more benign feature. This case highlights the importance of consideration of MAS as an uncommon but important cause of neonatal cholestasis. Early diagnosis may allow for prompt recognition and treatment of other endocrinopathies.

Biotinidase deficiency: Spectrum of molecular, enzymatic and clinical information from newborn screening Ontario, Canada (2007-2014).

Untreated profound biotinidase deficiency results in a wide range of clinical features, including optic atrophy, cutaneous abnormalities, hearing loss and developmental delay. Ontario, Canada incorporated this treatable deficiency in newborn screening over the past 8years. This study elucidates the molecular, biochemical, and clinical findings from the pilot project. Information from initial screens, serum biotinidase activity level assays, molecular testing, and family history for 246 positive newborns screens were analyzed. A mutation spectrum was created for the province of Ontario, including common mutations such as D444H, D444H/A171T, Q456H, C33fs, and R157H. Individuals with partial deficiency were separated into 3 groups: D444H homozygotes (Group 1); compound heterozygotes for D444H with another profound allele (Group 2); compound heterozygotes with two non-D444H alleles (Group 3). Biochemical phenotype-genotype associations in partial deficiency showed a significant difference in serum biotinidase activity in between any given two groups. Three children with partial deficiency discontinued biotin for varied lengths of time. Two of whom became symptomatic with abnormal gait, alopecia, skin rashes and developmental delay. A need for more congruency in diagnostic, treatment and educational practices was highlighted across the province. Heterogeneity and variation in clinical presentations and management was observed in patients with the partial deficiency.

Severe scoliosis in a patient with severe methylenetetrahydrofolate reductase deficiency.

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessively inherited inborn error of folate metabolism. We report a new patient with severe MTHFR deficiency who presented at age 4 months with early onset severe scoliosis associated with severe hypotonia. Markedly decreased MTHFR enzyme activity (0.3 nmoles CHO/mg protein/h; reference range>9) and compound heterozygous mutations (c. 1304T>C; p.Phe435Ser and c.1539dup; p.Glu514Argfs∗24) in the MTHFR gene confirmed the diagnosis. She was treated with vitamin B12, folic acid and betaine supplementation and showed improvements in her developmental milestones and hypotonia. To the best of our knowledge, this is the first patient with MTHFR deficiency reported with severe early onset scoliosis. Despite the late diagnosis and treatment initiation, she showed favorable short-term neurodevelopmental outcome. This case suggests that homocysteine measurement should be included in the investigations of patients with developmental delay, hypotonia and scoliosis within first year of life prior to organizing genetic investigations.

Virus de inmunodeficiencia humana y complicaciones neurológicas / VIH and neurologics complications

La infección por el virus de inmunodeficiencia humana (VIH) y el SIDA han aumentado su prevalencia en niños, los que presentan distintos tipos de compromiso neurológico, por infección viral directa o secundario al trastorno inmune. Se revisan las características de este compromiso en relación a mecanismos y formas de presentación, diagnóstico y su tratamiento. Se enfatiza la necesidad de acciones de prevención por parte del pediatra en el adolescente.