Systematic analysis of physical examination characteristics of 94 individuals with Joubert syndrome: Keys to suspecting the diagnosis.

Joubert syndrome (JS) is a neurodevelopmental disorder characterized by hypotonia and developmental delay, as well as the obligatory molar tooth sign on brain imaging. Since hypotonia and developmental delay are nonspecific features, there must be a high level of clinical suspicion of JS so that the diagnostic brain imaging and/or molecular testing for the >38 genes associated with JS is/are obtained. The goal of this study was to analyze clinical photographs of a cohort of patients with JS to define a list of physical examination features that should prompt investigation for JS. Analysis of photographs from 94 individuals with JS revealed that there is a recognizable pattern of facial features in JS that changes over time as individuals age. Macrocephaly, head tilting even when looking straight ahead, eye movement abnormalities (oculomotor apraxia, nystagmus, strabismus), and ptosis are common in those with JS. Distinctive features in younger children include triangular-shaped open mouth with tongue protrusion; in older children and adults, mandibular prognathia and prominent nasal bridge are common.

A structured genetics rotation for pediatric residents: an important educational opportunity.

PURPOSE: As the integral role of genetics in health and disease becomes increasingly understood, pediatricians must incorporate genetic principles into their care of patients. Structured exposure to genetics during residency may better equip future pediatricians to meet this goal. METHODS: Pediatric interns in the Johns Hopkins pediatric residency program have the option to spend one week immersed in clinical genetics by attending outpatient clinics and seeing inpatient consults. A pretest assessing clinical genetics knowledge is given before the rotation and compared with an identical post-test. Interns have a "scavenger hunt" to introduce genetic resources useful to pediatricians and complete a logbook of patient experiences. An evaluation is completed at the end of the rotation. RESULTS: Since the selective started in July 2016, 50 interns have participated. Average pretest score was 2.5/5 compared with a post-test score of 4.3/5, p < 0.0001. Interns saw on average ten patients and four different diagnoses. Overall evaluation was 4.4 on a 5-point scale, 5 being "excellent." CONCLUSION: This experience suggests that a structured rotation in genetics provides pediatric interns with an opportunity to learn basic clinical genetics knowledge and skills and see patients whom they may otherwise not encounter during residency.

Outcomes of cases with 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency - Report from the Inborn Errors of Metabolism Information System.

INTRODUCTION: 3-Methyl crotonyl CoA carboxylase (3MCC) deficiency is an inborn error of leucine metabolism whose detection was increased with the advent of expanded newborn screening. While most NBS-identified infants appear clinically normal, prior studies suggest a possible increased risk for developmental or metabolic abnormalities. As yet, no predictive markers are known that can identify children at risk for biochemical or developmental abnormalities. METHOD: All available 3-MCC cases diagnosed by newborn screening in the Inborn Errors of Metabolism Information System (IBEM-IS) were reviewed for markers that might be predictive of outcome. RESULTS: A limited number of cases were identified with traditional biochemical symptoms including acidosis, hyperammonemia or lactic acidosis, and 15% of those with available developmental information had recorded developmental disabilities not clearly attributable to other causes. There was no correlation between newborn screening (NBS) C5OH level and presence of metabolic, newborn, later-life or developmental abnormalities in these cases. DISCUSSION: This sample, obtained from the IBEM-IS database, attempts to avoid some of the ascertainment bias present in retrospective studies. An increase in developmental abnormalities and in traditionally described metabolic symptoms remains apparent, although no specific biochemical markers appear predictive of outcome. The role that prevention of fasting plays in outcome cannot be ascertained. These data suggest that C5OH level found on newborn screening by itself is not sufficient for diagnostic or predictive purposes.

The remarkable journey of one female individual with ornithine transcarbamylase deficiency diagnosed post-mortem.

Urea cycle disorders (UCDs) comprise a group of inborn errors of metabolism with impaired ammonia clearance and an incidence of ~1:35 000 individuals. First described in the 1970s, the diagnosis and management of these disorders has evolved dramatically. We report on a 59-year-old woman with a UCD who contributed to advances in the understanding and treatment of this group of disorders. This individual was diagnosed with carbamoyl phosphate synthetase 1 deficiency based on a biochemical assay under a research context predating genetic sequencing, treated longitudinally as having this metabolic disorder, and was among the first participants to trial UCD pharmaceutical therapies. She ultimately succumbed to a SARS-CoV-2 infection while maintaining unexpectedly normal ammonium levels. Postmortem genetic testing revealed ornithine transcarbamylase deficiency. This individual's contributions to the field of UCDs is discussed herein.