The Frequency of Lysosomal Acid Lipase Deficiency in Children With Unexplained Liver Disease

Abstract

Objectives: Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study.

Methods: Patients (aged 3 months-18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D(<0.02), intermediate (0.02-0.37) or normal (>0.37). Asecond dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result.

Results: A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (<1%). LAL activity was normal in 634 (78%) and intermediate in 174 (21%) patients. LAL-D was identified in 2 siblings aged 15 and 6 years born to unrelated parents. Dyslipidemia, liver steatosis, and mild increase in aminotransferases were common features in these patients. Moreover, the 15-year-old patient showed growth failure and microvesicular steatosis, portal inflammation, and bridging fibrosis in the liver biopsy. Based on 795 families, 2 siblings in the same family were identified as LAL-D cases, making the prevalence of LAL-D in this study population, 0.1% (0.125%-0.606%). In the repeated measurement (76/174), LAL activity remained at the intermediate level in 38 patients.

Conclusions: Overall, the frequency of LAL-D patients in this study (0.1%) suggests that LAL-D seems to be rare even in the selected high-risk population.

C1 [Kuloglu, Zarife; Kansu, Aydan; Selbuz, Suna] Ankara Univ, Sch Med, Dept Pediat Gastroenterol Hepatol & Nutr, Ankara, Turkey.

[Kalayci, Ayhan G.] Ondokuz Mayis Univ, Sch Med, Dept Pediat Gastroenterol Hepatol & Nutr, Samsun, Turkey.

[Sahin, Gulseren] Dr Sami Ulus Childrens Hosp, Dept Pediat Gastroenterol Hepatol & Nutr, Ankara, Turkey.

[Kirsaclioglu, Ceyda Tuna] Haematol Oncol Training & Res Hosp, Ankara Child Hlth Dis, Turkish Republ Hlth Minist, Dept Pediat Gastroenterol Hepatol & Nutr, Ankara, Turkey.

[Demiroren, Kaan] Yuzuncu Yil Univ, Fac Med, Dept Pediat Gastroenterol Hepatol & Nutr, Van, Turkey.

[Dalgic, Buket] Gazi Univ Univ, Dept Pediat Gastroenterol Hepatol & Nutr, Ankara, Turkey.

[Kasirga, Erhun] Celal Bayar Univ, Fac Med, Dept Pediat Gastroenterol Hepatol & Nutr, Manisa, Turkey.

[Onal, Zerrin] Univ Med Sci, Bakirkoy Dr Sadi Konuk Res & Training Ctr, Dept Pediat Gastroenterol Hepatol & Nutr, Istanbul, Turkey.

[Islek, Ali] Ataturk Univ, Fac Med, Dept Pediat Gastroenterol Hepatol & Nutr, Erzurum, Turkey.

[Eren, Esra] Ondokuz Mayis Univ, Sch Med, Samsun, Turkey.

[Hosnut, Ferda Ozbay] Dr Sami Ulus Childrens Hosp, Ankara, Turkey.

[Urganci, Nafiye; Usta, Ayse Merve] Sisli Etfal Training & Res Hosp, Istanbul, Turkey.

[Yaman, Aytac] Haematol Oncol Training & Res Hosp, Ankara Child Hlth Dis, Turkish Republ Hlth Minist, Ankara, Turkey.

[Ozkan, Tanju] Uludag Univ, Fac Med, Bursa, Turkey.

[Bozbulut, Eksi] Gazi Univ, Fac Med, Ankara, Turkey.

[Dogan, Guzide] Celal Bayar Univ, Fac Med, Manisa, Turkey.

[Arslan, Duran] Erciyes Univ, Fac Med, Kayseri, Turkey.

[Akcam, Mustafa] Suleyman Demirel Univ, Sch Med, Isparta, Turkey.

[Isik, Ishak Abdurrahman] Antalya Training & Res Hosp, Antalya, Turkey.

[Ecevit, Cigdem Omur; Erdemir, Gulin] Dr Behcet Uz Children Dis & Surg Training & Res H, Izmir, Turkey.

[Usta, Yusuf] Mersin Univ, Fac Med, Mersin, Turkey.

[Ozgur, Taner] Uludag Univ, Fac Med, Bursa, Turkey.

[Ozcay, Figen; Gulsan, Meltem] Baskent Univ, Fac Med, Ankara, Turkey.

[Balamtekin, Necati] Guhane Training & Res Hosp, Ankara, Turkey.

[Ozturk, Yesim] Dokuz Eylul Univ, Fac Med, Izmir, Turkey.

[Cantez, Serdar] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.

[Gulerman, Fulya; Guven, Burcu] Kirikkale Univ, Fac Med, Kirikkale, Turkey.

[Ustundag, Gonca Handan] Bulent Ecevit Uni, Fac Med, Zonguldak, Turkey.

[Emiroglu, Halil Haldun] Selcuk Univ, Fac Med, Konya, Turkey.

[Karacabey, Neslihan] Erciyes Univ, Fac Med, Kayseri, Turkey.

[Comba, Atakan] Hitit Univ, Fac Med, Corum, Turkey.

[Aydogan, Aysen Uncuoglu] Kocaeli Univ, Sch Med, Kocaeli, Turkey.

[Gokce, Selim] Bezmialem Univ, Fac Med, Istanbul, Turkey.

[Kuyum, Pinar] Dokuz Eylul Univ, Fac Med, Izmir, Turkey.

[Tosun, Mahya Sultan] Denizli State Hosp, Denizli, Turkey.

[Tokgoz, Yavuz] Adnan Menderes Univ, Fac Med, Adnan, Turkey.

[Yuksekkaya, Hasan] Necmenttin Erbakan Univ, Fac Med, Ankara, Turkey.

[Tumgor, Gokhan; Agin, Mehmet] Cukurova Univ, Fac Med, Ankara, Turkey.

[Eren, Makbule] Eskisehir Osmangazi Univ, Fac Med, Eskisehir, Turkey.

[Baran, Masallah] Izmir Tepec Training & Res Hosp, Izmir, Turkey.

[Gumus, Meltem] Konya Egitim Konya Training & Res Hosp, Konya, Turkey.

[Canan, Oguz] Adana Baskent Univ, Adana, Turkey.

[Kocamaz, Halil] Pamukkale Univ, Fac Med, Denizli, Turkey.

[Cakir, Murat] Karadeniz Tech Univ, Fac Med, Trabzon, Turkey.

[Hizli, Samil; Balci Sezer, Oya] Kecioren Training & Res Hosp, Ankara, Turkey.

[Dogan, Yasar; Deveci, Ugur] Firat Univ, Fac Med, Elazig, Turkey.

[Celtik, Coskun] Sifa Univ, Izmir, Turkey.