Natural history and management of liver dysfunction in lysosomal storage disorders

Table 1 Lysosomal storage disorders: Classification and clinical features

Diseases	Cardinal features	Degree of hepatosplenomegaly	Liver involvement
Diseases with major liver dysfunction: Sphingolipid and lipid storage disorders
Gaucher	Bone and lung infiltration, neurological (type II), nonneurological (type I), and intermediate (type III) forms; Paralytic squint (type II), Oculomotor apraxia/horizontal supranuclear gaze palsy (type III); Bone marrow failure, hematolymphoid malignancy (type I); Lymphadenopathy (type I)	Moderate to marked	Neonatal cholestasis, cirrhosis, portal hypertension, adenoma, hepatocellular carcinoma
Niemann-Pick A and B	Lung infiltration, neurological (type A) and nonneurological (type B); Cherry red spot (50%); Lymphadenopathy (type A)	Moderate to marked	Fetal hydrops (type A), cirrhosis, portal hypertension
Niemann-Pick C	Vertical supranuclear gaze palsy; Neurodegeneration	Moderate to marked	Neonatal cholestasis, fetal hydrops, liver failure, cirrhosis, portal hypertension
Lysosomal acid lipase deficiency	Steatorrhea, adrenal calcification (50%); Abnormal lipid profile	Mild to moderate	Asymptomatic hypertransaminasemia, liver failure
Diseases without major liver dysfunction
Group 1: Sphingolipid and lipid storage disorders
GM gangliosidosis	Neuroregression, dysostosis, cherry red spot	Absent to mild	Asymptomatic hepatomegaly
Farber	Subcutaneous nodules, joint involvement	Mild to moderate	Asymptomatic hepatomegaly
Group 2: Mucolipidoses
Mucolipidoses I, II and III	Seizures and cherry red spot (type I), kyphoscoliosis, joint contractures, dysostosis, cardiomyopathy	Mild to moderate	Asymptomatic hepatomegaly
Group 3: Glycoprotein storage disorders
Galactosialodosis	Mimics GM gangliosidosis, mental retardation	Mild to moderate	Asymptomatic hepatomegaly
Fucosidosis	Angiokeratoma, mental retardation	Mild to moderate	Asymptomatic hepatomegaly
α-Mannosidosis	Deafness, mental retardation	Mild to moderate	Asymptomatic hepatomegaly
Group 4: Mucopolysaccharidoses
Mucopolysaccharidoses I,II, III, IV, VI, VII	Coarse facies, corneal clouding (types I, IV, VII), mental retardation (types I, III, VII), dysostosis (types I, IV, VI), cardiomyopathy	Mild to moderate. Absent in milder variants	Asymptomatic hepatomegaly