Table 3.
Sterol concentrations in cerebrospinal fluid (CSF)
| Systematic Name | Common Name (Abbreviation) | Control (n = 5) |
CTX (n = 5) |
CDCA (n = 3) |
Note | |||
|---|---|---|---|---|---|---|---|---|
| Mean | Range | Mean | Range | Mean | Range | |||
| GC-MS | ||||||||
| Total cholest-5-en-3β-ol | Total cholesterol | 2.4 μg/ml | 1.5–3.3 | 5.6 μg/ml | 2.1–7.5 | 4.5 μg/ml | 4.1–4.7 | |
| Total 5α-cholestan-3β-ol | Total 5α-cholestanol | 2.9 ng/ml | 2.9–3.0 | 19.7 ng/ml | 1.7–47.2 | 5.4 ng/ml | 0.3–11.3 | |
| Total cholest-5-ene-3β,7α-diol | Total 7α-hydroxycholesterol (7α-HC) | 1.29 ng/ml | 1.12–1.42 | 10.62 ng/ml | 1.05–37 | 1.16 ng/ml | 0.3–2.87 | |
| Total cholest-5-ene-3β,(25R)26-diol | Total 27-hydroxycholesterol (27-HC) | 1.23 ng/ml | 0.73–1.94 | 0 | - | 0 | - | a |
| LC-MS (all values in ng/ml and for free oxysterols) | ||||||||
| Monohydroxycholesterols | ||||||||
| Cholest-5-ene-3β,7α-diol | 7α-Hydroxycholesterol (7α-HC) | 0.16 | 0.09–0.21 | 0.69 | 0.12–2.66 | 0.16 | 0.05–0.27 | |
| 7α-Hydroxycholest-4-en-3-one | 7α-Hydroxycholestenone (7α-HCO) | 0.00 | - | 1.48 | 0.14–6.09 | 0.04 | 0.02–0.07 | a,b,d |
| Cholest-5-ene-3β,24S-diol | 24S-Hydroxycholesterol (24S-HC) | 0.00 | 0–0.01 | 0.09 | 0–0.23 | 0.03 | 0.01–0.07 | d |
| Cholest-5-ene-3β,25-diol | 25-Hydroxycholesterol (25-HC) | 0.00 | - | 1.97 | 0–6.34 | 1.43 | 0–4.28 | d |
| Cholest-5-ene-3β,(25R)26-diol | 27-Hydroxycholesterol (27-HC) | 0.02 | 0.01–0.03 | 0.00 | - | 0.00 | - | a,d |
| Dihydroxycholesterols and dihydroxycholestenones | ||||||||
| 7α,12α-Dihydroxycholest-4-en-3-one | 7α,12α-Dihydroxycholestenone (7α,12α-diHCO) | 0.03 | 0–0.08 | 8.76 | 0.32–31.97 | 0.13 | 0.1–0.15 | a,d |
| 7α,24-Dihydroxycholest-4-en-3-one | 7α,24-Dihydroxycholestenone (7α,24-diHCO) | 0.00 | - | 0.00 | - | 0.00 | - | d |
| 7α,25-Dihydroxycholest-4-en-3-one | 7α,25-Dihydroxycholestenone (7α,25-diHCO) | 0.00 | - | 0.17 | 0.12–0.24 | 0.09 | 0.04–0.13 | a,b,d |
| 7α,(25R)26-Dihydroxy-cholest-4-en-3-one | 7α,27-Dihydroxycholestenone (7α,27-diHCO) | 0.01 | 0–0.03 | 0.01 | 0.00–0.04 | 0.00 | - | d |
| Trihydroxycholestenones | ||||||||
| 7α,12α,25-Trihydroxy-cholest-4-en-3-one | 7α,12α,25-Trihydroxycholestenone (7α,12α,25-triHCO) | 0.11 | 0.07–0.23 | 0.43 | 0.17–0.86 | 0.05 | 0.00–0.1 | a,c,d,e |
| Monohydroxycholestenoic and oxocholestenoic acids | ||||||||
| 3β-Hydroxycholest-5-en-(25R)26-oic acid | 3β-Hydroxycholestenoic acid (3β-HCA) | 0.61 | 0.41–0.87 | 0.00 | - | 0.01 | 0.00–0.02 | a,d |
| 3-Oxocholest-4-en-(25R)26-oic acid | 3-Oxocholestenoic acid | 0.00 | - | 0.00 | - | 0.00 | - | d |
| Dihydroxycholestenoic and monohydroxyoxocholestenoic acids | ||||||||
| 3β,7α-Dihydroxycholest-5-en-(25R)26-oic acid | 3β,7α-Dihydroxycholestenoic acid (3β,7α-diHCA) | 0.00 | - | 0.00 | - | 0.00 | - | d |
| 7α-Hydroxy-3-oxocholest-4-en-(25R)26-oic acid | 7α-Hydroxy-3-oxocholestenoic acid (7αH,3O-CA) | 13.21 | 6.93–30.36 | 0.10 | 0.00–0.17 | 0.00 | - | a,d |
| 3β,7α-Dihydroxycholest-5-en-(25S)26-oic acid | 3β,7α-Dihydroxycholestenoic acid (25S) (3β,7α-diHCA (25S)) | 0.00 | - | 0.00 | - | 0.00 | - | d |
| 7α-Hydroxy-3-oxocholest-4-en-(25S) 26-oic acid | 7α-Hydroxy-3-oxocholestenoic acid(25S) (7αH,3O-CA (25S)) | 2.85 | 1.59–7.21 | 0.20 | 0.12–0.32 | 0.11 | 0.08–0.17 | a |
| 3β,25-Dihydroxycholest-5-en-26-oic acid and/or 3β,25,X-Trihydroxycholest-5-en-Y-one | 3β,25-Dihydroxy-cholestenoic acid and/or 3β,25,X-Trihydroxycholest-5-en-Y-one | 0.00 | - | 0.00 | - | 0.00 | - | e,f,g |
| Dihydroxyoxocholestenoic acids | ||||||||
| 7α,12α-Dihydroxy-3-oxocholest-4-en-26-oic acid and/or 7α,12α,25-Trihydroxycholest-4-ene-3,24-dione | 7α,12α-Dihydroxy-3-oxocholestenoic acid and/or 7α,12α,25-Trihydroxycholest-4-ene-3,24-dione | 0.36 | 0.16–0.73 | 0.50 | 0.00–1.85 | 0.00 | - | e,d,f,h |
| 7α,24-Dihydroxy-3-oxocholest-4-en-26-oic acid | 7α,24-Dihydroxy-3-oxocholestenoic acid | 0.20 | 0.11–0.48 | 0.01 | 0.00–0.03 | 0.01 | 0.00–0.01 | a,d,f |
| 7α,25-Dihydroxy-3-oxocholest-4-en-26-oic acid | 7α,25-Dihydroxy-3-oxocholestenoic acid | 0.76 | 0.49–1.6 | 0.00 | - | 0.00 | - | a,d,f |
| Dien-sterols | ||||||||
| 3β-Hydroxycholesta-5,7-dien-26-oic acid and/or 3β-Hydroxycholesta-5,Y-dien-26-oic acid | 3β-Hydroxycholest-5,7-dienoic acid and/or 3β-Hydroxycholesta-5,Y-dien-26-oic acid | 0.00 | - | 0.00 | - | 0.00 | - | d |
| 3-Oxocholesta-4,6-dien-26-oic acid and/or 3-Oxocholesta-4,Y-dien-26-oic acid | 3-Oxocholesta-4,6-dienoic acid and/or 3-Oxocholesta-4,Y-dien-26-oic acid | 2.08 | 0.87–3.84 | 0.01 | 0.00–0.02 | 0.03 | 0.00–0.08 | a,b,d |
| 12α-Hydroxycholesta-4,6-dien-3-one | 12α-Hydroxycholesta-4.6-dien-3-one (12α-HC-4,6-dien-3-one) | 0.00 | - | 4.59 | 0.54–11.97 | 0.00 | - | a,d |
| 24 or 25-Hydroxycholesta-4,6-dien-3-one and/or 24 or 25-Hydroxycholesta-4,8-dien-3-one | 24 or 25-Hydroxycholesta-4,6-dien-3-one and/or 24 or 25-Hydroxycholesta-4,8-dien-3-one | 0.00 | - | 0.00 | - | 0.00 | - | d |
CTX, cerebrotendinous xanthomatosis; CDCA, chenodeoxycholic acid.
CTX group: Patients CTX 4–8, CDCA group: Patients CTX 1, CTX 2, and CTX 5
a
P < 0.0125 for comparison between controls and untreated patients with CTX.
b
P < 0.0125 for comparison between controls and patients with CTX treated with 750 mg/day CDCA.
c
P < 0.0125 for comparison between drug-naive and CDCA-treated patients with CTX.
d
Values below limit of quantification of 0.1 ng/ml in CSF or 0.5 ng/ml in serum.
e
Identification based on exact mass retention time and MS3 spectrum in the absence of an authentic standard.
f
MS3 spectra do not allow the differentiation between the isomers/epimers.
g
The position of the additional hydroxy group is not determined.
h
In CTX, there is no direct synthesis of (25R)26-oic acids and most likely a 25-hydroxy-3,24-dione structure is present.