Cheng-Hung Huang1, Pao-Chin Chiu2, Hao-Chuan Liu3, Yung-Hsiu Lu1, Jun-Kai Huang3, Min-Ji Charng4, Dau-Ming Niu5. 1. Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, R.O.C; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. 2. Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. 3. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. 4. School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. Electronic address: mjcharng@vghtpe.gov.tw. 5. Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, R.O.C; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. Electronic address: dmniu1111@yahoo.com.tw.
Abstract
BACKGROUND: Clinical observation and treatment of children with homozygous familial hypercholesterolemia (HoFH) has rarely been reported. We report clinical observations and treatment of 10 ethnic Chinese children with HoFH due to low-density lipoprotein receptor (LDLR) defect. OBJECTIVES: In children with HoFH, we evaluated the response to conventional cholesterol-lowering drug therapy and performed LDLR gene analysis. METHODS: A retrospective review of lipid profile changes in pediatric patients diagnosed with HoFH seen in our pediatric endocrinology outpatient clinic was performed. HoFH was diagnosed by molecular study of these patients and their parents. RESULTS: One novel (c.64del G) and 12 known mutations were found in the LDLR gene. Mutation of p.C308Y was the most common and was found in 26% of the studied alleles.Seven patients had fair responses to conventional drug therapy (high-dose statin with ezetimibe) with a reduction of 50% or more of the total cholesterol levels. The low-density lipoprotein-cholesterol levels of three patients decreased to lower than 160 mg/dL. One who had a good response to conventional drug therapy developed significant atheromatous plaques (largest plaque: 7.4 × 2.7 cm) in the extracranial carotid arteries and myocardial ischemia changes at 11 years old. CONCLUSION: The results suggest that despite aggressive therapy, many patients are not well controlled; atherosclerosis may progress, and novel therapies are required.
BACKGROUND: Clinical observation and treatment of children with homozygous familial hypercholesterolemia (HoFH) has rarely been reported. We report clinical observations and treatment of 10 ethnic Chinese children with HoFH due to low-density lipoprotein receptor (LDLR) defect. OBJECTIVES: In children with HoFH, we evaluated the response to conventional cholesterol-lowering drug therapy and performed LDLR gene analysis. METHODS: A retrospective review of lipid profile changes in pediatric patients diagnosed with HoFH seen in our pediatric endocrinology outpatient clinic was performed. HoFH was diagnosed by molecular study of these patients and their parents. RESULTS: One novel (c.64del G) and 12 known mutations were found in the LDLR gene. Mutation of p.C308Y was the most common and was found in 26% of the studied alleles.Seven patients had fair responses to conventional drug therapy (high-dose statin with ezetimibe) with a reduction of 50% or more of the total cholesterol levels. The low-density lipoprotein-cholesterol levels of three patients decreased to lower than 160 mg/dL. One who had a good response to conventional drug therapy developed significant atheromatous plaques (largest plaque: 7.4 × 2.7 cm) in the extracranial carotid arteries and myocardial ischemia changes at 11 years old. CONCLUSION: The results suggest that despite aggressive therapy, many patients are not well controlled; atherosclerosis may progress, and novel therapies are required.