Objective: Dyslipidemia is a disease characterized by a genetic or multifactorial disorder of lipid and/or lipoprotein metabolism. Childhood dyslipidemia is a rare genetic metabolic disease that can cause serious cardiovascular disease and seriously endanger children's health.
Methods: We retrospectively analyzed the clinical data of 10 patients with dyslipidemia who were admitted to the Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine from August in 2009 to August in 2017. Seven probands and two of their parents underwent next generation sequencing.
Result: There were differences in the clinical phenotype of 10 probands, and four probands, P2 to P5, had strong pathogenic mutations.
1. Clinical phenotypes: (1) 10 cases of proband were from Zhejiang Province, there was 5 males and 5 females; (2) The median age of diagnosis is 4.7 years old; The age of onset clinical symptoms in hyperchylomicronemia were early; (3) The clinical manifestations were mostly xanthomas. Three of probands (P1,P2 and P10) were found that the creamy plasma appearance; (5) Among the clinical phenotypes, 5 cases were hypercholesterolemia, 4 cases were combined hyperlipidemia, and 1 case was hypertriglyceridemia.Two of them were low high density lipoproteinemia.
2. Molecular genetic results:LPL gene mutation was found in P2; the mutation of LDLR gene were found in P3. There were ABCG5 gene mutations in P4 and P5 (1 missense mutation and 1 nonsense mutation). There was a complex heterozygous mutation in P4, one is c.1166 G> A, a homozygous missense mutation of ABCG5, and both father and mother were heterozygous carriers. Another is heterozygous missense mutations of c.5002G>A and c.3121C>G of ABCA1. In P5, there was a homozygous nonsense mutation of c.751C>T in ABCG5. Both parents (normal phenotype) were heterozygous carriers.None of the above gene mutations were new mutations, and no pathogenic gene was found in P6 and P7.
3. Treatment and prognosis: They were all given dietary control of cholesterol intake, infants were controlled long-chain fatty acid intake. xanthoma of 2 sitosterolemia cases(P4 and P5) became larger. But after controlling animal and phytosterol intake simultaneously, the xanthoma has improved.No early-onset coronary heart disease has been found in these probands.
Conclusion: Children with dyslipidemia have diverse clinical phenotype and high genetic heterogeneity.Genetic testing can increase the accuracy of clinical diagnosis and contribute to early diagnosis and treatment of diseases.Sitosterolemia may be an important cause of hypercholesterolemia in China.The restriction of cholesterol and phytosterol intake should be suggested for sitosterolemia.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology