Initial assessment and ongoing monitoring of lysosomal acid lipase deficiency in children and adults: Consensus recommendations from an international collaborative working group.

BACKGROUND: Lysosomal acid lipase (LAL) deficiency is an ultra-rare, progressive, autosomal recessive disorder. Functional mutations in LIPA, the gene that encodes LAL, result in accumulation of cholesteryl esters and triglycerides in hepatocytes and in the macrophages of the intestines, vascular endothelial system, and numerous other organs. LAL deficiency has a broad clinical spectrum; children and adults can present with dyslipidemia, liver enzyme elevations, hepatosplenomegaly, hepatic steatosis, liver fibrosis and/or cirrhosis, and vascular disease, which may lead to significant morbidity and premature mortality in some patients. Given the systemic involvement and the wide range of healthcare specialists who manage patients with LAL deficiency, there is a need for guidelines to assess and monitor disease involvement. OBJECTIVES: To provide a set of recommendations for the initial assessment and ongoing monitoring of patients with LAL deficiency to help physicians in various disciplines effectively manage the disease based on the observed presentation and progression in each case. METHODS: A group of internationally recognized healthcare specialists with expertise in clinical genetics, pathology, hepatology, gastroenterology, cardiology, and lipidology convened to develop an evidence-based consensus of best practices for the initial assessment and ongoing monitoring of children and adults with LAL deficiency, regardless of treatment status; infants with LAL deficiency have been excluded from these guidelines because they require specialized care. RESULTS: The authors present guidance for the assessment and monitoring of patients with LAL deficiency based on age and disease manifestations that include the hepatic, cardiovascular, and gastrointestinal systems. A schedule for ongoing monitoring of disease progression is provided. In addition, the need to establish an interdisciplinary and integrated care team to optimize the approach to managing this systemic disease is highlighted. CONCLUSIONS: There is currently no published guidance on the assessment and monitoring of patients with LAL deficiency. These consensus recommendations for the initial assessment and ongoing monitoring of children and adults with LAL deficiency are intended to help improve the management of these patients.

Integrating lipid screening with ideal cardiovascular health assessment in pediatric settings.

Pediatric lipid screening and management with the aim of reducing and preventing adult disease is an internationally accepted concept, and guidelines have been published in several countries. However, implementation by the practicing pediatric community in the United States has been less than expected and delays have been attributed to uncertainty among providers. Reduced screening rates have also been reported for conditions contributing to arterial wall pathology such as obesity, hypertension, and prediabetes despite accumulating evidence that detection and intervention can lead to risk reversal. Consistent with graded and evidence-based national guidelines for comprehensive cardiovascular risk assessment and management, we present how the American Heart Association ideal cardiovascular health (ICVH) model can be integrated with lipid screening, and how it can be compatible with comprehensive pediatric lipidology practice and enhanced familial hypercholesterolemia detection. Since being introduced and retrospectively validated in adults and children in cross-sectional studies, ICVH evaluates thresholds for seven ideal health metrics representing measurements of obesity, dyslipidemia, diabetes risk, and blood pressure, and includes exercise, diet, and smoking behaviors. When each metric is valued as a point, the maximum health score is 7, but national surveys have shown unacceptable low scores in adolescence. Inverse correlation of scores with arterial structural change supports use of ICVH as a collection of treatable targets forming a cardiovascular prevention construct including and supporting lipid screening in pediatric settings, but implementation in clinical practice requires more expertise and administrative support than lipid screening alone.

Probabilistic Modeling Approach to Reducing Healthcare Costs With Reflex Testing.

OBJECTIVE: Statistical methods can be utilized to optimize the order for reflex diagnostic testing to attenuate patient and hospital costs without affecting quality of care. Our objective is to demonstrate the method of developing an order for testing and to apply this method to an illustrative example. METHODS: An algorithm was developed for minimizing costs for any given number of diagnostic tests, and it was retrospectively applied to a sample. RESULTS: The actual scenario of using both tests on all patients was compared to 2 other hypothetical reflex testing approaches: all patients are given 1 test, and those patients who tested negative were then given the second test. The 2 scenarios would have saved 37.1% and 17.4% in testing costs, respectively. CONCLUSION: These calculations could be applied to numerous situations to reduce costs for patients and hospitals. We propose that this methodology would be best used in conjunction with any existing quality improvement initiatives.

Self-assessment of sexual maturation in children and adolescents with diabetes mellitus.

OBJECTIVE: To evaluate the reliability of a self-assessment tool as a surrogate means for estimating phase of sexual maturation in children and adolescents with diabetes mellitus. METHODS: Children and adolescents between 8 and 16 years of age with the diagnosis of type 1 or type 2 diabetes mellitus were recruited from the pediatric endocrinology clinic at a children's hospital. Participants were given a series of gender-appropriate drawings representing the 5 Tanner stages of sexual maturation for genital development in boys and breast and genital development in girls and asked to select the illustration that best represented their current maturity stage. The self-assessments were compared with physical examination findings by pediatric endocrinologists. Demographic and clinical data including age, race, hemoglobin A1c level, type of diabetes, and body mass index were also collected. Agreement rates between participants and physician assessment were compared. A level of agreement greater than 80% and a kappa coefficient greater than 0.61 were considered substantial. RESULTS: Eighty-seven children and adolescents completed the study. Agreement rates for girls were greater than 80%. Agreement rates for boys were 76%. All kappa coefficients for boys and girls were greater than 0.61, corresponding to good agreement. However, peripubertal participants overestimated their sexual maturity rating almost half the time. The role of age, metabolic control (as measured by hemoglobin A1c), race, type of diabetes, and body mass index did not influence a participant's ability to accurately assess sexual maturity. CONCLUSION: While useful in mid- to late-pubertal youth with diabetes, this self-assessment tool does not appear to be helpful in identifying the early stages of puberty.