RESUMEN
PURPOSE OF REVIEW: To provide an overview about the molecular basis of familial hypercholesterolemia. RECENT FINDINGS: Familial hypercholesterolemia is a common hereditary cause of premature coronary heart disease. It has been estimated that 1 in every 250 individuals has heterozygous familial hypercholesterolemia and that fewer than 1% of patients with familial hypercholesterolemia have been identified across the globe. If heterozygous familial hypercholesterolemia is left untreated, it is likely that coronary heart disease will manifest clinically prior to the age of 55 years and that half of all patients will prematurely die from the consequences of myocardial infarction. It is crucial to understand the molecular basis of familial hypercholesterolemia to diagnose familial hypercholesterolemia properly. SUMMARY: The phenotype of familial hypercholesterolemia is caused by more than 1700 mutations the LDLR, apoB and PCSK9 genes, which explains approximately 85% of familial hypercholesterolemia cases. By means of next-generation sequencing, an increasing number of mutations in established and putative novel genes associated with this phenotype have been identified.
RESUMEN
OBJECTIVE: The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults. METHODS: Investigators reviewed medical records of LAL D patients ages ≥5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset. RESULTS: A total of 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first disease-related abnormality was 9.0 years (range 0-42); mean age at diagnosis was 15.2 years (range 1-46). Twenty-nine (60%) were male patients, and 27 (56%) were <20 years of age at the time of consent/assent. Serum transaminases were elevated in most patients with 458 of 499 (92%) of alanine aminotransferase values and 265 of 448 (59%) of aspartate aminotransferase values above the upper limit of normal. Most patients had elevated low-density lipoprotein (64% patients) and total cholesterol (63%) at baseline despite most being on lipid-lowering therapies, and 44% had high-density lipoprotein levels below the lower limit of normal. More than half of the patients with liver biopsies (nâ=â31, mean age 13 years) had documented evidence of steatosis (87%) and/or fibrosis (52%). Imaging assessments revealed that the median liver volume was â¼1.15 multiples of normal (MN) and median spleen volume was â¼2.2 MN. Six (13%) patients had undergone a liver transplant (ages 9-43.5 years). CONCLUSION: This study provides the largest longitudinal case review of patients with LAL D and confirms that LAL D is predominantly a pediatric disease causing early and progressive hepatic dysfunction associated with dyslipidemia that often leads to liver failure and transplantation.