Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients.

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD. METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review. RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at the time of data collection was 9.0 years (interquartile range = 5.3-15.9 years, range = fetal to 31.8 years). A total of 24 different TANGO2 alleles were observed. Patients showed normal development in early infancy, with progressive delay in developmental milestones thereafter. Symptoms included ataxia, dystonia, and speech difficulties, typically starting between the ages of 1 to 3 years. A total of 46/71 (65%) patients suffered metabolic crises, and of those, 30 (65%) developed cardiac crises. Metabolic crises were significantly decreased after the initiation of B-complex or multivitamin supplementation. CONCLUSION: We provide the most comprehensive review of natural history of TDD and important observational data suggesting that B-complex or multivitamins may prevent metabolic crises.

Setting a research agenda for vascular Ehlers-Danlos syndrome using a patient and stakeholder engagement model.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare, syndromic, heritable condition with life-threatening complications that include aortic and arterial aneurysms, dissection, and rupture. This study describes the formation of the vEDS Research Collaborative and methods used for stakeholder engagement. METHODS: The vEDS Research Collaborative was established with an engagement award from the Patient-Centered Outcomes Research Institute to create a framework for a patient-researcher partnership. Between October 1, 2017, and September 30, 2018, the Collaborative used the Patient-Centered Outcomes Research Institute Engagement Rubric to conduct stakeholder engagement to develop a patient-centered research agenda. A modified Delphi technique was used to develop and to refine research topics and questions, gathering input from all stakeholders during three rounds of feedback. RESULTS: Four topic areas were deemed important: mental health and quality of life issues, creating a care team, a holistic approach to vEDS management (medical and surgical), and pregnancy management. An online survey to rank a list of 12 research questions in these topic areas in order of importance was disseminated. The questions were ranked in order of importance through an online survey (N = 197 responses). The survey showed a high degree of alignment in the top priorities among stakeholders. There was a high degree of interest in pragmatic clinical trials evaluating medical management options and health-related quality of life outcomes. CONCLUSIONS: The vEDS Research Collaborative has built a sustainable, coalition model of patient and stakeholder engagement, supported by the vEDS community, to identify a patient-centered, prioritized list of research questions. In articulating a shared vision for the future of vEDS research, the Collaborative has laid the groundwork for developing research protocols aligned with the highest priority questions for the individuals affected by this serious condition that can be translated into future clinical trials.

Immunizations, neonatal jaundice, and animal-induced injuries.

PURPOSE OF REVIEW: Published studies during the past year about three topics important to the pediatric clinician-- immunizations, neonatal jaundice, and animal-induced injuries-are concisely reviewed. RECENT FINDINGS: Recent updates regarding vaccines including the questionable link with autism, implementation of universal influenza vaccination for young children, the efficacy of pneumococcal vaccine against invasive disease, and new information on pertussis, varicella, hepatitis A, hepatitis B, measles, and rotavirus vaccination are discussed. No association between measles/mumps/rubella vaccine or thimerosal-containing pertussis vaccine and autism is evident. Universal influenza vaccination for children 6 to 23 months of age will be recommended for the 2004-2005 flu season, and this implementation should reduce significant school absenteeism as well as complications seen last year including encephalopathy, seizures, respiratory failure, and pneumonia. Pneumococcal vaccine significantly reduces rates of invasive pneumococcal vaccine in healthy and HIV-infected children, although it does not appear to greatly affect otitis media rates. A reduction in post-vaccine febrile seizures appears to be present since the introduction of acellular pertussis vaccine. Multiple outbreaks in varicella have been reported since the introduction of the varicella vaccine, and a booster vaccination may be necessary in the future. Methods for detecting and preventing severe neonatal hyperbilirubinemia are reviewed, as well as anticipated recommendations from the American Academy of Pediatrics for the detection and management of hyperbilirubinemia. High bilirubin levels in preterm infants may result in hearing dysfunction and developmental impairment. The American Academy of Pediatrics has recommended a higher level of monitoring for newborn jaundice and treatment of hyperbilirubinemia in an effort to prevent kernicterus and sequelae from elevated bilirubin levels, including post-discharge follow-up appointment by day 3 to 5 of age. Dog bites in children with resultant post-traumatic stress disorder, rabies, and salmonellosis from pet reptiles in the home are also addressed. Clinicians need to be aware of the risk for rabies bites, need to recognize that dog bites in children appear to cause post-traumatic stress disorder in more than half of cases, and need to know how to educate patients on how to prevent salmonellosis from pet reptiles and amphibians. SUMMARY: Progress has been made in immunizations, especially immunization for influenza, pneumonia, and pertussis. It is recommended that monitoring for neonatal hyperbilirubinemia be more thorough to prevent the consequences of this condition. Rabies, post-traumatic stress disorder from dog bites, and salmonellosis associated with pet reptiles constitute an important area for patient education.