Early onset lysosomal acid lipase deficiency presenting as secondary hemophagocytic lymphohistiocytosis: Two infants treated with sebelipase alfa - 27/04/18

Doi : 10.1016/j.clinre.2018.03.012

Ermelinda Santos Silva ^a,^b,^{^{1
Both authors equally contributed to this manuscript.},}^⁎ , Maja Klaudel-Dreszler ^c,^{^{1
Both authors equally contributed to this manuscript.}} , Agnieska Bakuła ^c , Teresa Oliva ^d , Tereza Sousa ^e , Paula Cristina Fernandes ^f , Anna Tylki-Szymańska ^g , Elena Kamenets ^h , Esmeralda Martins ^b,ⁱ , Piotr Socha ^c
^a Gastroenterology unit, Pediatrics Division, Child and Adolescent Department, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto, Largo da Maternidade, 4050-651 Porto, Portugal
^b Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal
^c Department of Gastroenterology, Hepatology, Nutritional Disorders and Paediatrics, Children's Memorial Health Institute, Warsaw, Poland
^d Pediatrics Division, Instituto Português de Oncologia do Porto, Portugal
^e Laboratorial Hematology Division, Instituto Português de Oncologia, Porto, Portugal
^f Pediatric Intensive Care Division, Child and Adolescent Department, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto, Portugal
^g Department of Paediatrics, Nutrition and Metabolic Disorders, Children's Memorial Health Institute, Warsaw, Poland
^h Research Centre for Medical Genetics, Moscow, Russia
ⁱ Metabolic Diseases Unit, Pediatrics Division, Child and Adolescent Department, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto, Portugal

^⁎Corresponding author. Gastroenterology unit, Pediatrics Division, Child and Adolescent Department, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto, Largo da Maternidade, 4050-651 Porto, Portugal.Gastroenterology unit, Pediatrics Division, Child and Adolescent Department, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto, Largo da Maternidade, 4050-651 Porto, Portugal.

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Summary

Two unrelated infants were diagnosed with and initially treated for hemophagocytic lymphohistiocytosis (HLH), but progressed to cholestasis and liver failure. Early onset lysosomal acid lipase deficiency (EO-LAL-D) was suspected due to lymphocytes with cytoplasmic vacuolation and/or adrenal calcifications and confirmed by enzymatic and genetic analysis. Enzyme replacement therapy with sebelipase alfa was implemented, but both children died, despite initial improvement. Since this inborn error of metabolism progresses rapidly in infants, early diagnosis is crucial, and appropriate treatment should be started as soon as possible. The authors suggest that the diagnosis of EO-LAL-D should be considered in infants with symptoms of HLH.

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Keywords : Hemophagocytic lymphohistiocytosis, Early onset lysosomal acid lipase deficiency, Wolman disease, Hepatosplenomegaly, Neonatal cholestasis, Sebelipase alfa

Abbreviations : ALT, AST, CESD, EO-LALD, FHL, HLH, HSCT, rhLAL, LDL, LAL-D, GGT