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] |