RESUMEN
PURPOSE: Describe the clinical and molecular findings of patients with Kabuki syndrome (KS) who present with hypoglycemia due to congenital hyperinsulinism (HI), and assess the incidence of KS in patients with HI. METHODS: We documented the clinical features and molecular diagnoses of 9 infants with persistent HI and KS via a combination of sequencing and copy-number profiling methodologies. Subsequently, we retrospectively evaluated 100 infants with HI lacking a genetic diagnosis, for causative variants in KS genes. RESULTS: Molecular diagnoses of KS were established by identification of pathogenic variants in KMT2D (n = 5) and KDM6A (n = 4). Among the 100 infants with HI of unknown genetic etiology, a KS diagnosis was uncovered in one patient. CONCLUSIONS: The incidence of HI among patients with KS may be higher than previously reported, and KS may account for as much as 1% of patients diagnosed with HI. As the recognition of dysmorphic features associated with KS is challenging in the neonatal period, we propose KS should be considered in the differential diagnosis of HI. Since HI in patients with KS is well managed medically, a timely recognition of hyperinsulinemic episodes will improve outcomes, and prevent aggravation of the preexisting mild to moderate intellectual disability in KS.
Asunto(s)
Anomalías Múltiples/genética , Hiperinsulinismo Congénito/genética , Proteínas de Unión al ADN/genética , Cara/anomalías , Enfermedades Hematológicas/genética , Histona Demetilasas/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Enfermedades Vestibulares/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/fisiopatología , Preescolar , Hiperinsulinismo Congénito/complicaciones , Hiperinsulinismo Congénito/diagnóstico , Hiperinsulinismo Congénito/fisiopatología , Cara/fisiopatología , Femenino , Predisposición Genética a la Enfermedad , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/fisiopatología , Humanos , Lactante , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual/fisiopatología , Masculino , Mutación , Patología Molecular , Estudios Retrospectivos , Enfermedades Vestibulares/complicaciones , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/fisiopatologíaRESUMEN
The author Diva D. De Leon was incorrectly listed as instead of Diva D. De Leó-Critchlow in the original version of this paper.
RESUMEN
BACKGROUND: Newborn Screening Connect (NBS Connect) is a web-based self-reported patient registry and resource for individuals and families affected by disorders included in the newborn screening panel. NBS Connect was launched in 2012 by Emory University after years of planning and grassroots work by professionals, consumers, and industry. Individuals with phenylketonuria (PKU), maple syrup urine disease (MSUD) or tyrosinemia (TYR) have been recruited through distribution of outreach materials, presentations at parent organization meetings and direct recruitment at clinic appointments. Participants complete online profiles generating data on diagnosis, treatment, symptoms, outcomes, barriers to care, and quality of life. Resources such as education materials, information on the latest research and clinical trials, recipes, interactive health tracking systems, and professional support tools are described. In addition, to examine the ability of NBS Connect to generate data that guides hypothesis-driven research, data pertaining to age at diagnosis, bone health, and skin conditions in individuals with PKU were assessed. The objective of this paper is to describe the development of NBS Connect and highlight its data, resources and research contributions. RESULTS: In September 2016, NBS Connect had 442 registered participants: 314 (71%) individuals with PKU, 68 (15%) with MSUD, 20 (5%) with TYR, and 40 (9%) with other disorders on the NBS panel. Age at diagnosis was less than 4 weeks in 285 (89%) of 319 respondents to this question and between 1 month and 14 years in 29 (9%) individuals. Of 216 respondents with PKU, 33 (15%) had a DXA scan in the past year. Of 217 respondents with PKU, 99 (46%) reported at least one skin condition. CONCLUSIONS: NBS Connect was built and refined with feedback from all stakeholders, including individuals with inherited metabolic disorders. Based on patient-reported data, future studies can be initiated to test hypotheses such as the relationship between PKU and skin conditions. Patient registries like NBS Connect can inform hypothesis-driven research, contributing to knowledge generation and following the current trend in moving from traditional medicine towards evidence-based practice. NBS Connect will help clinicians understand long-term outcomes of rare disorders, contributing to better patient care and quality of life.