Kolesterol ester depo hastalığının olası ön göstergelerinin araştırılması ve lizozomal asit lipazın referans aralığının belirlenmesi
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Dosyalar
Tarih
2016
Yazarlar
Dergi Başlığı
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Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç: Kolesterol ester depo hastalığı nadir görülen, otozomal resesif kalıtılan lizozomal depo hastalığıdır. Hücre içi triaçilgliserol ve kolesterol esterlerin hidrolizinden sorumlu lizozomal asid lipaz (LAL) enziminin eksikliği veya yetersizliği sonucu oluşur. Sunulan çalışmanın birinci amacı klinik şüphe (hepatik disfonksiyon ve/veya dislipidemi varlığı) olan olgularda LAL eksikliğinin araştırılmasıdır. LAL aktivitesi düşük saptanan olgularda bu düşüklüğün bağlantılı olabileceği biyobelirteçleri belirlemek ve LAL için Türk popülasyonuna ait referans aralığını belirlemek, çalışmamızın ikincil amaçlarıdır. Araştırılan biyobelirteçlerin başında lizozomal hastalıkların tanı ve izleminde kullanılan "kitotriozidaz", non-alkolik steatohepatitde apoptozisten sorumlu "cytokeratin-18", ateroskleroz ve non alkolik steatohepatitte değerli bir gösterge olan hsCRP, ve lipid peroksidasyonunda önemli rolleri olan TBARS ve MPO ile ilişkinin araştırılması planlandı. Gereç ve Yöntem: Çalışmaya 0- 18 yaş aralığında toplam 360 çocuk alındı. 40'ı kontrol; 320'si hepatomegali(+/-), transaminaz yüksekliği(+/-) ve/veya hiperlipidemi saptanan non-obez tarama olguları idi. Bu hastalardan LAL aktivitesi <0.6 nmol/ml/saat Grup 1'i oluşturdu; LAL aktivitesi {601}0.6 nmol/ml/saat Grup 2'i meydana getirdi (Şekil 1). Olguların yaş, cinsiyet, ailede hiperlipidemi öyküsü gibi demografik verileri ve fizik muayene bulguları kaydedildi. Hasta dosyalarından lipid profili, hemogram, biyokimya, koagulasyon parametreleri, abdomen USG ve viral seroloji (HbsAg, Anti Hbs, Anti HCV) sonuçları kaydedildi. LAL aktivitesi çalışılması için kapiller kuru kan örneği; LAL aktivitesi düşük saptanan olgularda kitotriosidaz, hsCRP, cytokeratin-18, MPO ve TBARS çalışılması için eş zamanlı 2 cc düz tüpe kan ayrıldı. Referans enzim olarak sfingomyelinaz çalışıldı. LAL enzim düzeyi enzim inhibisyon (Lalistat 2) yöntemi ile çalışıldı. Bulgular: Çalışmaya katılan tüm olguların yaş ortancası 5 ( 0-18) yıl saptandı. Bu olguların 154 (%42)'ü erkek, 206 (%58)'sı kız idi. Tarama grubunda akraba evliliği ve ailesel hiperlipidemi anlamlı yüksek saptandı (p<0.05). Boy- ve ağırlık- SDS ortancaları tarama grubunda anlamlı düşük bulundu (p<0.05). Tarama grubunda LAL düzeyi kontrol grubu ile karşılaştırıldığında anlamlı düşük bulundu (p<0.001), fakat LAL eksikliği (LAL<0.03 nmol/ml/saat) olan olgu saptanmadı. Kontrol ve tarama grupları karşılaştırıldığında hemoglobin ve trombosit parametreleri tarama grubunda anlamlı düşük saptandı (p<0.05). Beklendiği gibi tarama grubunda AST, ALT, total bilirubin düzeyi anlamlı yüksek bulundu (p<0.05). Grup 1 ile kontrol grubu karşılaştırıldığında Grup 1'de ailevi hiperlipidemi öyküsü, ALT, AST ve total bilirubin anlamlı yüksek; Hb, lökosit ve trombosit sayıları anlamlı düşük bulundu (p<0.05). Ayrıca, Grup 1'de LDL-kolesterol ve trigliserid anlamlı yüksek, HDL-kolesterol anlamlı düşük saptandı (p<0.05). Kontrol ve Grup 1 TBARS düzeyleri (sırası ile: 11.25 (3.75-49.38),14.38 (5-37.5) mmol/ml) anlamlı olarak farklı bulundu (p=0.035). Diğer parametrelerle ilişki saptanmadı. Ayrıca, hepatomegalisi olanlarda hastalarda ortanca LAL aktiviteleri anlamlı olarak düşük saptandı (p=0.013). Tüm çalışma grubu değerlendirildiğinde: LAL düzeyi ile LDL, trigliserid ve ALT arasında negatif korelasyon saptandı. Ayrıca ALT ve trigliserid düzeylerinin sırası ile 1.8 ve 1.4 kat artışları LAL aktivitesinde anlamlı bir düşüşe neden oldukları görüldü. Kadın ve erkek için aynı olmak üzere referans aralık 0.26-6.2 nmol/ml/saat olarak belirlendi. Sonuçlar:KEDH tanısı alan olgu tanımlanmadı. LAL düşüklüğünün ALT, LDL-kolesterol ve trigliserid ile negatif korelasyon gösterdiği saptandı.LAL düşüklüğü TBARS ile ilişkili bulundu. Eve gidecek mesaj: Pediatrik yaş grubunda dislipidemi ve/veya transaminaz yüksekliği LAL enzim aktivitesinde düşüklük ile birliktedir.
Introduction and Aim: Cholesterol ester storage disease is a rare, lysosomal storage disease with autosomal recessive inheritance. It results from the deficiency or insufficiency of lysosomal acid lipase (LAL) enzyme in charge of the hydrolysis of intracellular triacylglycerol and cholesterol esters. The initial objective of the present study is to search for LAL deficiency in the cases with clinical suspicion (hepatic dysfunction and /or existence of dislipidemia). In the cases determined to have low LAL activity, the secondary objectives of our study are to determine the biomarkers with which this lowness will be associated and to determine the reference range of Turkish population for LAL. At the lead of the searched biomarkers, it was planned to search the relationship with “kitotriozidaz” used in the diagnosis and follow up of lysosomal diseases, with “cytokeratin-18” responsible for apoptosis in non-alcoholic steatohepatitis, with hsCRP which is a valuable marker in atherosclerosis and non-alcoholic steatohepatitis, and with TBARS and MPO which have important roles in lipid peroxidation. Material-Methods: A total of 360 children were included in the study with the age range of 0-18. 40 of them were included in the control group and other 320 were the non-obese scanning cases diagnosed with hepatomegaly (+/-), transaminase elevation (+/-) and/ or hyperlipidemia. Of these patients, those with LAL activity of <0.6 nmol/ml/hour formed Group 1; those with LAL activity of ≥0.6 nmol/ml/hour formed Group 2. The cases demographic data such as age, gender, family history of hyperlipidemia and results of physical examination were recorded. From the patient files, the results of lipid profile, hemogram, biochemistry, coagulation parameters, abdomen USG and viral serology (HbsAg, Anti Hbs, Anti HCV) were recorded. To study LAL activity, capillary dry blood sample was sorted out; in cases with low LAL activity blood was simultaneously sorted out into 2 cc plain tube to study kitotriosidasis , hsCRP, cytokeratin-18, MPO and TBARS. Sfingomyelinaz was studied as reference enzyme. LAL enzyme level was studied with enzyme inhibition (Lalistat 2 ) method. Results: Average age of all cases in the study was found to be 5 years (0-18). 154 of the cases (42%) were male and 206 of them (58%) were female. In the scan group, kin marriage and familial hyperlipidemia were found to be significantly high (p<0.05). Height and weight SDS averages were found to be significantly low in the scan group (p<0.05). LAL level in the scan group were found to be significantly low in comparison to control group (p<0.001), yet no case with LAL deficiency (LAL < 0.03 nmol/ml/hour) was found. When the control and scan groups were compared, hemoglobin and thrombocyte parameters were found to be significantly low in scan group (p<0.05). As might be expected, AST, ALT total bilirubin levels were found to be significantly high in scan group (p<0.05). When Group 1 was compared to control group, family history of hyperlipidemia, ALT, AST and total bilirubin were found to be significantly high ; Hemoglobin, leukocyte and platelets numbers were found to be significantly low in Group 1 (p<0.05). Also in Group 1, LDL-cholesterol and trigliserid were found to be significantly high, HDL-cholesterol to be significantly low (p<0.05). TBARS levels of Control group and Group 1were found to be significantly different (11.25 (3.75-49.38),14.38(5-37.5) mmol/ml, respectively) (p=0.035). No relationship was found with other parameters. Besides, in patients with hepatomegali, LAL activities were found to be significantly low (p=0.013). when the whole study group was assessed, a negative correlation was determined between LAL level and LDL, and between trigliserid and ALT. Also, it was seen that 1.8 and 1.4 times increase of ALT and trigliserid levels respectively caused a significant decrease in LAL activity. Reference range was determined to be 0.26-6.2 nmol/ml/hour, as being the same for males and females. Conclusion: • No patient with KEDH diagnosis was determined. • LAL lowness was found to show negative correlation with ALT, LDL-cholesterol and trigliserid. • LAL lowness was found to be related to TBARS. The message to home: Dyslipidemia and /or transaminase elevation is together with LAL enzyme activity lowness in pediatric age group.
Introduction and Aim: Cholesterol ester storage disease is a rare, lysosomal storage disease with autosomal recessive inheritance. It results from the deficiency or insufficiency of lysosomal acid lipase (LAL) enzyme in charge of the hydrolysis of intracellular triacylglycerol and cholesterol esters. The initial objective of the present study is to search for LAL deficiency in the cases with clinical suspicion (hepatic dysfunction and /or existence of dislipidemia). In the cases determined to have low LAL activity, the secondary objectives of our study are to determine the biomarkers with which this lowness will be associated and to determine the reference range of Turkish population for LAL. At the lead of the searched biomarkers, it was planned to search the relationship with “kitotriozidaz” used in the diagnosis and follow up of lysosomal diseases, with “cytokeratin-18” responsible for apoptosis in non-alcoholic steatohepatitis, with hsCRP which is a valuable marker in atherosclerosis and non-alcoholic steatohepatitis, and with TBARS and MPO which have important roles in lipid peroxidation. Material-Methods: A total of 360 children were included in the study with the age range of 0-18. 40 of them were included in the control group and other 320 were the non-obese scanning cases diagnosed with hepatomegaly (+/-), transaminase elevation (+/-) and/ or hyperlipidemia. Of these patients, those with LAL activity of <0.6 nmol/ml/hour formed Group 1; those with LAL activity of ≥0.6 nmol/ml/hour formed Group 2. The cases demographic data such as age, gender, family history of hyperlipidemia and results of physical examination were recorded. From the patient files, the results of lipid profile, hemogram, biochemistry, coagulation parameters, abdomen USG and viral serology (HbsAg, Anti Hbs, Anti HCV) were recorded. To study LAL activity, capillary dry blood sample was sorted out; in cases with low LAL activity blood was simultaneously sorted out into 2 cc plain tube to study kitotriosidasis , hsCRP, cytokeratin-18, MPO and TBARS. Sfingomyelinaz was studied as reference enzyme. LAL enzyme level was studied with enzyme inhibition (Lalistat 2 ) method. Results: Average age of all cases in the study was found to be 5 years (0-18). 154 of the cases (42%) were male and 206 of them (58%) were female. In the scan group, kin marriage and familial hyperlipidemia were found to be significantly high (p<0.05). Height and weight SDS averages were found to be significantly low in the scan group (p<0.05). LAL level in the scan group were found to be significantly low in comparison to control group (p<0.001), yet no case with LAL deficiency (LAL < 0.03 nmol/ml/hour) was found. When the control and scan groups were compared, hemoglobin and thrombocyte parameters were found to be significantly low in scan group (p<0.05). As might be expected, AST, ALT total bilirubin levels were found to be significantly high in scan group (p<0.05). When Group 1 was compared to control group, family history of hyperlipidemia, ALT, AST and total bilirubin were found to be significantly high ; Hemoglobin, leukocyte and platelets numbers were found to be significantly low in Group 1 (p<0.05). Also in Group 1, LDL-cholesterol and trigliserid were found to be significantly high, HDL-cholesterol to be significantly low (p<0.05). TBARS levels of Control group and Group 1were found to be significantly different (11.25 (3.75-49.38),14.38(5-37.5) mmol/ml, respectively) (p=0.035). No relationship was found with other parameters. Besides, in patients with hepatomegali, LAL activities were found to be significantly low (p=0.013). when the whole study group was assessed, a negative correlation was determined between LAL level and LDL, and between trigliserid and ALT. Also, it was seen that 1.8 and 1.4 times increase of ALT and trigliserid levels respectively caused a significant decrease in LAL activity. Reference range was determined to be 0.26-6.2 nmol/ml/hour, as being the same for males and females. Conclusion: • No patient with KEDH diagnosis was determined. • LAL lowness was found to show negative correlation with ALT, LDL-cholesterol and trigliserid. • LAL lowness was found to be related to TBARS. The message to home: Dyslipidemia and /or transaminase elevation is together with LAL enzyme activity lowness in pediatric age group.
Açıklama
Anahtar Kelimeler
Lizozomal Asid Lipaz, Kolesterol Ester Depo Hastalığı, Kitotriozidaz, CK-18, hsCRP, MPO, TBARS, Lysosomal Acid Lipase, Wolman Disease, Cholesterol Ester Storage Disease, Chitotriosidase
