Cardiac Evaluation of Children With a Family History of Sudden Death.

BACKGROUND: After sudden death occurs in the young, first-degree family members should undergo clinical screening for occult cardiac disease, but the diagnostic yield from screening is not well-defined in the United States. OBJECTIVES: The purpose of this study was to determine the clinical predictors of cardiac diagnosis in children referred for evaluation following a sudden death in the family. METHODS: Patients referred for a family history of sudden death were evaluated in a retrospective review from a tertiary pediatric referral center. RESULTS: Among 419 pediatric relatives of 256 decedents, 27% of patients were diagnosed with a disease or had a clinical finding of uncertain significance. Patients were diagnosed with heritable cardiac disease in 39 cases (9.3%). Nonheritable cardiac disease was diagnosed in another 5.5% of patients. Clinical findings of uncertain significance were present in 52 patients (12.4%), including abnormal electrophysiological test results (41 of 52) or imaging test results (11 of 52). Among patients diagnosed with a heritable cardiac disease, the nearest affected relative was almost always a first-degree relative (37 of 39, 95%). The strongest predictors for a successful diagnosis in the patient were an abnormal electrocardiogram and a first-degree relationship to the nearest affected relative (odds ratios: 24.2 and 18.8, respectively). CONCLUSIONS: Children referred for a family history of sudden death receive cardiac disease diagnoses (14%), but clinical findings of uncertain significance increase the challenge of clinical management. The importance of a diagnosis in first-degree affected relatives supports the clinical practice of testing intervening family members first when patients are second- or higher-degree relatives to the decedent.

Polysomnography Outcomes after Supraglottoplasty in Children with Obstructive Sleep Apnea.

OBJECTIVE: Laryngomalacia has been reported to contribute to the severity of obstructive sleep apnea (OSA) in children. It is unclear if surgical treatment of laryngomalacia improves polysomnography (PSG) outcomes in these patients. The objective of this study is to report the impact of supraglottoplasty on PSG parameters in children with laryngomalacia-related OSA. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: Historical cohort study of consecutive children with laryngomalacia who underwent supraglottoplasty and who had undergone overnight PSG before and after surgery. RESULTS: Forty-one patients were included in the final analysis: 22 (53.6%) were male, and 19 (46.3%) were female. The mean ± SEM age of patients at preoperative PSG was 1.3 ± 0.89 years (range, 0.003-2.9). In entire cohort, the mean obstructive apnea-hypopnea index score was reduced from 26.6 events/h before supraglottoplasty to 7.3 events/h after surgery (P = .003). Respiratory disturbance index was reduced from 27.3 events/h before supraglottoplasty to 7.8 events/h after surgery (P = .003). The percentage of REM sleep decreased from 30.1% ± 2.4 to 24.8% ± 1.3 (P = .04). Sleep efficiency was improved (P = .05). CONCLUSION: Overall, supraglottoplasty significantly improved several PSG outcomes in children with laryngomalacia. However, mild to moderate OSA was still present postoperatively in most children. This suggested a multifactorial cause for OSA in this population.

Hepatic HKDC1 Expression Contributes to Liver Metabolism.

Glucokinase (GCK) is the principal hexokinase (HK) in the liver, operating as a glucose sensor to regulate glucose metabolism and lipid homeostasis. Recently, we proposed HK domain-containing 1 (HKDC1) to be a fifth HK with expression in the liver. Here, we reveal HKDC1 to have low glucose-phosphorylating ability and demonstrate its association with the mitochondria in hepatocytes. As we have shown previously that genetic deletion of HKDC1 leads to altered hepatic triglyceride levels, we also explored the influence of overexpression of HKDC1 in hepatocytes on cellular metabolism, observing reduced glycolytic capacity and maximal mitochondrial respiration with concurrent reductions in glucose oxidation and mitochondrial membrane potential. Furthermore, we found that acute in vivo overexpression of HKDC1 in the liver induced substantial changes in mitochondrial dynamics. Altogether, these findings suggest that overexpression of HKDC1 causes mitochondrial dysfunction in hepatocytes. However, its overexpression was not enough to alter energy storage in the liver but led to mild improvement in glucose tolerance. We next investigated the conditions necessary to induce HKDC1 expression, observing HKDC1 expression to be elevated in human patients whose livers were at more advanced stages of nonalcoholic fatty liver disease (NAFLD) and similarly, found high liver expression in mice on diets causing high levels of liver inflammation and fibrosis. Overall, our data suggest that HKDC1 expression in hepatocytes results in defective mitochondrial function and altered hepatocellular metabolism and speculate that its expression in the liver may play a role in the development of NAFLD.