Table 2: Known WD and CESD mutations.

Disease Mutation Exon Base Change Amino Acid Change Remaining Enzyme Activity (% of WT) Phenotypic Presentations Ref.
WD E3∆8bp 3 8 bp deletion Nonsense “deficient” Hepatosplenomegaly, adrenal calcifications, abdominal distension, vomiting, steorrhea, failure to thrive. Death at 3 months (heart failure) [128]
WD Y22X 3 C to G Tyr to X <1% Abdominal distension with hepatosplenomegaly, frequent diarrhea and vomiting. Calcified and enlarged adrenals, hepatosplenomegaly. Death at 114 days [129]
WD R44X 3 C to T Arg to X Not reported Not reported [34]
WD E4skip 4 Unknown Nonsense <4% Bilateral adrenal calcifications. Death at 4 months [46]
WD G60V 4 G to T Gly to Val <1% Calcified adrenals, hepatosplenomegaly [53]
WD W116X 4 G to A Trp to X <1% Liver necrosis/fibrosis, vacuolated lymphocytes. Bone marrow showed lipid laden histiocytes. Enlarged and calcified adrenal glands. Death at 4 months due to liver and renal failure [46]
WD E4∆2bp 4 TC deletion Nonsense Undetectable Hepatosplenomegaly, adrenal calcifications, abdominal distension, vomiting, steorrhea, failure to thrive. Death at 2.5 months (respiratory and cardiac arrest) [128]
WD S106X 5 C deletion Ser to X <1% Pregnancy terminated after chorionic villus biopsy demonstrated lipase deficiency. Previous sibling died at 3 months and had hepatosplenomegaly, diarrhea, anemia, and calcified adrenals [53]
WD fs177 6 T to TT Nonsense Near absent Failure to thrive, diarrhea, hepatomegaly [46]
WD L179P 6 T to C Leu to Pro <5% Pregnancy terminated and diagnosis was confirmed in cultured fibroblasts. Previous siblings with WD had hepatosplenomegaly, failure to thrive, and adrenal calcification [130]
WD fs219 7 T deletion Nonsense <1% Liver necrosis/fibrosis, vacuolated lymphocytes. Bone marrow showed lipid laden histiocytes. Enlarged and calcified adrenal glands. Death at 4 months due to liver and renal failure [46]
WD Q277X 8 C to T Gln to X Undetectable Hepatosplenomegaly, adrenal calcification, failure to thrive [131]
WD E8SJM+1 8 G to A 24 AA deletion <1% Hepatomegaly, diarrhea, failure to thrive [54]
WD E8SJM-3 8 C to T 24 AA deletion Undetectable Hepatosplenomegaly, adrenal calcification, failure to thrive [131]
WD Y303X 10 T to A Tyr to X Undetectable Hepatomegaly, failure to thrive, diarrhea, adrenal gland calcifications [55]
CESD c.57_60delTGAG 2 TGAG deletion Nonsense Low (No units provided) Hepatomegaly, microvesicular steatosis in the hepatic parenchyma. Portal tracts had foamy macrophages [132]
CESD Q64R 4 A to G Gln to Arg 3-8% Hepatomegaly, hypercholesterolemia, and hypoalphalipoproteinemia. Mild fibrosis in the liver with microvacuolated histiocytes [55]
CESD G66V 4 G to T Gly to Val Not reported Vacuolized hepatocytes, hypercholesterolaemia and hyptertriglycerdaemia (diagnosed at 22 years of age) [59]
CESD N98S 4 A to G Asn to Ser Not reported Hepatomegaly presentation at 26 years of age. Liver biopsy revealed foamy macrophages [133]
CESD R100G 4 A to G Arg to Gly Not reported Not reported [34]
CESD H108P 4 A to C His to Pro Not reported No symptoms until 44 years of age. Increased total cholesterol and aminotransferases. Hepatomegaly presented 1 year with some subcutaneous tumors on the chest and abdominal wall [74]
CESD H108R 4 A to G His to Arg 2.7% Diagnosed postmortem after death at 57 years of age. Hepatomegaly and moderate splenomegaly presented at 18 months of age. Liver biopsies revealed lipid storage typical of CESD [134]
CESD fs112 5 TC deletion Nonsense <15% Hepatic splenic enlargement evident at 11 years of age, not diagnosed till 22 years of age [46]
CESD P181L 6 C to T Pro to Leu Not reported Hepatomegaly, hypercholesterolaemia, hypertriglyceridemia. Cirrhosis and storage of birefringent material in hepatocytes [59]
CESD E7SJM 6 A to G 48 AA deletion Not reported Hepatomegaly, hypercholesterolaemia, hyptertriglycerdiaemia. Cirrhosis and storage of birefringent material in hepatocytes [59]
CESD G245X 7 G to T Gly to X <1% Pregnancy terminated after chorionic villus biopsy demonstrated lipase deficiency. Previous sibling died at 3 months and had hepatosplenomegaly, diarrhea, anemia, and calcified adrenals [53]
CESD T267I 7 C to T Thr to Ile 3-8% Hepatomegaly, hypercholesterolemia, and hypoalphalipoproteinemia. Mild fibrosis in the liver with microvacuolated histiocytes [55]
CESD E7SJM-2 7 A to G 48 AA deletion Not reported Hepatomegaly, hypercholesterolaemia, hypertriglyceridemia. Cirrhosis and storage of birefringent material in hepatocytes [59]
CESD N250H 7 A to C Asn to His 5.9% Hepatomegaly presented in middle school, but patient was diagnosed at 69 years of age. Cirrhosis of the liver. Liver also had foamy macrophages [135]
CESD L264P 7 T to C Leu to Cys <1% Massive hepatomegaly and splenomegaly. Vomiting and diarrhea a few days prior to hospital visit. Diagnosed at 11 years of age – evaluated at hospital due to gastroenteritis [136]
CESD S289C 8 C to G Ser to Cys 6% Hepatomegaly, chronic diarrhea, fever, weight loss. Adrenal calcifications. Sinusoidal fibrosis. Foamy histiocytes in the bone marrow. Cholesterol crystals in lysosome [46]
CESD L273S 8 T to C Leu to Ser Not reported Hepatosplenomegaly presentation at 5 years of age. Hypercholesterolaemia and hypertriglyceridemia presentation at 15 years of age [59]
CESD H274Y 8 C to T His to Tyr 3-7% N/A [137]
CESD E8SJM-1 8 G to A 24 AA deletion 1.2% Hepatomegaly. Fatty changes without macrovesicular steatosis of the liver [46]
CESD E10∆AG 10 AG deletion Nonsense Not reported Hepatosplenomegaly, hypercholesterolemia, hypertriglyceridemia, and elevated live function tests [57]
CESD E10∆C 10 C deletion Nonsense <1% Mildly enlarged liver. Diagnosed at 28 years of age [46]
CESD E10∆G 10 G deletion Nonsense 7% Hepatomegaly, hypercholesterolemia. Liver biopsy revealed cholesteryl esters in hepatocytes as well as foamy macrophages. Elevated LDL and triglyceride levels with reduced HDL [138]
CESD G321W 10 G to T Gly to Trp Undetectable Hepatosplenomegaly, adrenal calcifications, abdominal distension, vomiting, steorrhea, failure to thrive. Death at 2.5 months (respiratory and cardiac arrest) [128]
CESD G342R 10 G to A Gly to Arg 6% Hepatomegaly, chronic diarrhea, fever, weight loss. Adrenal calcifications. Sinusoidal fibrosis. Foamy histiocytes in the bone marrow. Cholesterol crystals in lysosome [46]
CESD L336P 10 T to C Leu to Pro 14.2% Hepatomegaly, elevated apoB levels [139]