Case Report: Wolman disease caused by LIPA variants in two Chinese infants and a focused literature synthesis

Abstract

Background Wolman disease is the severe infantile form of lysosomal acid lipase deficiency, caused by biallelic pathogenic variants in the Lysosomal Acid Lipase (LIPA) gene. It is rapidly progressive and often fatal within the first year of life without disease-specific therapy. Because early manifestations are non-specific, timely diagnosis remains challenging. Case presentation We report the cases of two Chinese male infants with genetically confirmed Wolman disease. Case 1 involved an 8-week-old infant—born to consanguineous parents—who presented with persistent diarrhea, recurrent low-grade fever, abdominal distension, hepatosplenomegaly, ascites, bilateral adrenal involvement, anemia, thrombocytopenia, hypoproteinemia, dyslipidemia, coagulopathy, and electrolyte disturbances. Liver biopsy showed diffuse hepatocyte vacuolization. Genetic testing identified a novel homozygous LIPA variant—c.285G > T/p.Trp95Cys—inherited from heterozygous carrier parents. Lysosomal acid lipase activity was markedly reduced to 0.62% of the normal control level. Case 2 involved an 11-week-old infant who presented with failure to thrive, poor feeding, abdominal distension, cough, progressive hepatosplenomegaly, ascites, bilateral adrenal calcifications, hepatic dysfunction, systemic inflammation, coagulopathy, anemia, and thrombocytopenia. He carried compound heterozygous LIPA non-sense variants, c.796G > T/p.Gly266* and c. 193C > T/p.Arg65*, inherited from his mother and father, respectively. Despite supportive care, both infants developed progressive multiorgan failure and died. Conclusion These cases expand the clinical and molecular spectrum of Wolman disease in Chinese infants and highlight important diagnostic challenges, including non-specific early manifestations and inflammatory presentations mimicking hematologic disorders. Recognition of the characteristic combination of hepatosplenomegaly, failure to thrive, dyslipidemia, adrenal calcification, reduced lysosomal acid lipase activity, and LIPA variants may facilitate early diagnosis. Timely identification is essential because early enzyme replacement therapy may alter the otherwise fatal natural course of this rapidly progressive disease.