Natural history and management of liver dysfunction in lysosomal storage disorders

Abstract

Lysosomal storage disorders (LSD) are a rare group of genetic disorders. The major LSDs that cause liver dysfunction are disorders of sphingolipid lipid storage [Gaucher disease (GD) and Niemann-Pick disease] and lysosomal acid lipase deficiency [cholesteryl ester storage disease and Wolman disease (WD)]. These diseases can cause significant liver problems ranging from asymptomatic hepatomegaly to cirrhosis and portal hypertension. Abnormal storage cells initiate hepatic fibrosis in sphingolipid disorders. Dyslipidemia causes micronodular cirrhosis in lipid storage disorders. These disorders must be keenly differentiated from other chronic liver diseases and non-alcoholic steatohepatitis that affect children and young adults. GD, Niemann-Pick type C, and WD also cause neonatal cholestasis and infantile liver failure. Genotype and liver phenotype correlation is variable in these conditions. Patients with LSD may survive up to 4-5 decades except for those with neonatal onset disease. The diagnosis of all LSD is based on enzymatic activity, tissue histology, and genetic testing. Enzyme replacement is possible in GD and Niemann-Pick types A and B though there are major limitations in the outcome. Those that progress invariably require liver transplantation with variable outcomes. The prognosis of Niemann-Pick type C and WD is universally poor. Enzyme replacement therapy has a promising role in cholesteryl ester storage disease. This review attempts to outline the natural history of these disorders from a hepatologist's perspective to increase awareness and facilitate better management of these rare disorders.

Keywords: Children; Cholesteryl ester; Gaucher; Lysosomal; Niemann-Pick; Wolman.

Figure 1

Pathogenesis of Gaucher disease. GD: Gaucher disease.

Figure 2

Histology of Gaucher disease. Red arrow shows Gaucher cells.

Figure 3

Pathogenesis of Niemann-Pick disease types A, B, and C. NPD: Niemann-Pick disease.

Figure 4

Fundus examination showing a cherry red spot (red arrow) with a background of white retina.

Figure 5

Histology in Niemann-Pick disease type B. Red arrow shows a foamy vacuolated histiocyte.

Figure 6

Infant with Niemann-Pick disease type C presenting as cholestasis, dilated abdominal veins, and massive hepatosplenomegaly.

Figure 7

Pathogenesis of lysosomal acid lipase deficiency. CESD: Cholesteryl ester storage disease; VLDL: Very low-density lipoproteins.

Figure 8

Computed tomography of the abdomen in an infant with Wolman disease showing bilateral adrenal calcifications.