Mutation Analysis Of Two Children With Xanthomatosis And Review Of The Literatures

Background and objectives:Xanthomatosis is a type of skin disease which is often associate d with lipid metabolic disorders.Children with xanthomatosis are rare,t he most common in inherited metabolic disease such as Familial hyp-ercholesterolemia,and it is Closely related to LDLR,ABCG5,ABCG8,PSCK9,and CYP27 A gene mutations.Children with those yellow lesions are associated with early atherosclerosis and coronary heart disease,even with the nervous system,digestive system damage,seriously affecting the health of them.We collected 2 cases of children with x-anthomatosis and review the literatures published on databases such as CKNI,WANFANG data,VIP data to domestic reports from 2000 t-o 2018 of 33 cases of children with xanthomatosis to analyzed,in o rder to further understand the incidence of the disease in our country,clinical characteristics,diagnosis and treatment,to improve clinical ph-ysicians and patients' understanding of the disease.Method:To collect clinical data(history,physical examination and family survey)of 2 patients with xanthomatosis diagnosed and treated in the dermatology clinic of Children's Hospital of Chongqing Medical University,conduct laboratory examination and imaging examination,detect the pathogenic gene,follow-up the therapy.Through the search of "children with xanthomatosis,xanthoma" and other keywords in CNKI,Wanfang and VIP database,and analysis systematically the 33 cases of children with xanthomatosis from 2000 to 2018 by retrieving the literatures.Result:Proband 1,female,1 year old and 5months,who was admitted to the dermatology clinic of our hospital in 2016 due to "yellowwish plaques on the hips of the limbs".When the child was 1 year old,there are yellow plaques on the wrists,ankles and buttocks,and the yellow plaques gradually increase,involving the underarms,buttocks,thighs,and armpits.There was no obvious abnormality in the system of the child,and there was no similar history in the family.Blood lipid examination showed an increase in total cholesterol(TC)and low-density lipoprotein(LDL),and no abnormalities were observed in blood routine,liver function kidney,cardiac ultrasound,and carotid ultrasound.The parents had normal blood lipid levels.The gene detection showed: c.751C>T(exon6)and c.1419delC(exon10)complex heterozygous mutation of ABCG5 gene,andc.1419delC(exon10)is a new variation.After 1 year of low-fat and low plant sterol diet,all the xanthomas disappeared,and TC and LDL level decreased slightly.Proband 2: Female,10 years old,who was admitted to the dermatology clinic of our hospital due to "eyelid,limb rash on the joints for10 years" in 2018,the child found yellowish plaques on the limbs after birth,did not pay attention,the rash gradually Increased,there are still new rashs after surgical resection of the external hospital.There was no obvious abnormality in the system of the child,and his father had a history of hyperlipidemia.Blood lipid examination showed that TC and LDL increased,blood routine,liver function kidney,cardiac color Doppler ultrasound,carotid ultrasound did not show obvious abnormalities,genetic testing showed: LDLR gene c.676T>C(exon4)and c.1474G>A(exon10)Compound heterozygous mutations.After treatment with fenofibrate 200mg*d,the TC after 3 months decreased slightly compared with the previous one,and there was no significant change in the rash.She is now continued to be treated with oral fenofibrate.Literature review results:This case summarizes 33 cases of children with xanthomatosis reported in China from 2000 to 2018,include 2 patients in this study,there are 35 cases in total.The age of 35 patients in China is 1month to 17 years old.The mean age of diagnosed is(9.61±5.90)years old;the average age of rash appeared was(4.31±4.50)years old;of the 35 patients,21(60%)were female and 14(40%)were male,the ratio of male to female is 3:2.Of the 35 cases,29 cases(82.86%)were genetically related,of which 23 cases were familial hypercholesterolemia(65.71 %).Among the 35 patients,7 cases(20%)had cardiovascular involvement,2(5.71%)had corneal ring,and 4(11.43%)had abnormal liver and spleen.Of the 35 patients,34 reported total cholesterol(TC)values in 34 patients,with an average of(16.22 ± 4.96)mmol/L,of which 34 cases(97.15%)were higher than normal;low density lipoprotein(LDL)values were reported.In 29 cases,the average was(12.29±4.41)mmol/L,27 cases(77.14%)were higher than the normal value;the cases of perfecting the detection of disease-causing genes were limited,including 9 cases of two probands in this article,a total of 9 cases were found,and LDLR gene mutation was found in 5 cases,3 cases of ABCG5 gene mutation and 1 case of ABCG8 gene mutation.Conclusion:1.Skin lesions in children with xanthomatosis occur earlier,but are often ignored,so that the condition can not be diagnosed in time and delay treatment.2.Familial hypercholesterolemia caused by mutation of LDLR gene is the most common primary disease of children with xanthomatosis,followed by sitosterolemia caused by mutation of ABCG5 gene.Mutation of exon 3and exon 4 of the LDLR gene in xanthomatosis plays animportant role in the pathogenesis,The mutation of LDLR gene has certain regional aggregation.The R446 X mutation of ABCG5 gene may be a domestic hot spot for mutation,providing prenatal genetic diagnosis the theoretical basis.3.Children with xanthomatosis are associated with a significant increase in TG and LDL levels,and even premature cardiovascular damage and other systemic damage.4.The principle of treatment of childhood xanthomatosis is to treat the primary disease and improve the prognosis of the cardiovascular system.When the primary disease is controlled,the lesions of most patients can subside.