Background
Methods
Patients
Family | I | II | ||
---|---|---|---|---|
Case No | 1 | 2 | 1 | 2 |
Gender
|
F
|
M
|
M
|
M
|
Age (years) | 54 | 50 | 31 | 29 |
Age at CTX diagnosis (years) | 37 | 32 | 24 | 23 |
Disease duration at neuromuscular study (years) | 49 | 45 | 21 | 17 |
Body height (cm) | 143 | 155 | 164 | 175 |
Body weight (kg) | 45 | 50 | 74 | 114 |
Genetic mutation (CYP 27 gene) | Homozygous: 305delC (exon 2) | Heterozygous: 1333C > T (exon 8) and IVS 7+1G > A (intron 7) | ||
Clinical manifestation | ||||
Tendinous xanthomatosis | + | + | + | + |
Cataracts | + | + | + | + |
Osteoporosis with multiple fractures | + | + | - | - |
Mental retardation | + | + | + | + |
Cerebellar sign | + | + | + | + |
Pyramidal sign | + | + | + | + |
Parkinsonism | + | + | - | - |
Glove-stock paresthesia | - | - | - | - |
Hyporefelxia | - | - | - | - |
Distal foot muscle atrophy | - | - | - | - |
Posture related problems | - | - | - | - |
Sphincter problems | - | - | - | - |
Sweating problems | - | - | - | - |
Nerve conduction study and electromyography study
Muscle biopsies
Skin biopsies and quantitation of skin innervation
Autonomic function assessments
Q-Sweat recordings
Results
NCS and EMG
Case | Median | Ulnar | Superficial radial | Peroneal | Tibial | Sural | H-reflex (N < 27.6) | |||
---|---|---|---|---|---|---|---|---|---|---|
Motor | Sensory | Motor | Sensory | |||||||
I-1 | R DL (ms) | 4.4 (N < 3.6) | 2.8 | 2.9 (N < 2.8) | 2.2 | 1.9 | 4.0 (N < 4.2) | 2.7 (N < 4.9) | Absent | 31.0 |
L DL (ms) | 4.4 | 3.0 | 2.5 | 2.9 | 1.7 | 4.0 | 3.7 | Absent | 30.4 | |
R CV (m/s) | 50 (N > 57.8) | 50 (N > 51.7) | 50 (N > 61.4) | 56 (N > 56.3) | 63 (N > 50) | 39 (N > 48.6) | 45 (N > 50.5) | Absent (N > 47.4) | ||
L CV (m/s) | 49 | 47 | 54 | 49 | 71 | 42 | 40 | Absent | ||
R Amp | 7.6 (N > 11.9) | 47 (N > 33) | 11 (N > 11.7) | 32 (N > 26.1) | 23 (N > 15) | 4.1 (N > 6.0) | 5.5 (N > 13.1) | Absent (N > 12.5) | ||
L Amp | 7.1 | 21 | 8.1 | 38 | 33 | 4.5 | 9.6 | Absent | ||
R F waves | 26.8-0.7 (N < 25.4) | 27.0-0.8 (N < 25.0) | 49.8-0.4 (N < 44.7) | 50.2-0.8 (N < 45.0) | ||||||
L F waves | 27.9-0.8 | 26.4-1.0 | 47.4-0.4 | 50.4-0.8 | ||||||
I-2 | R DL (ms) | 4.4 | 2.7 | 3.2 | 2.6 | 2.1 | 4.2 | 5.0 | Absent | 32.4 |
L DL (ms) | 4.0 | 2.8 | 3.0 | 2.2 | 1.8 | 3.9 | 3.3 | Absent | 32.6 | |
R CV (m/s) | 49 | 53 | 54 | 46 | 57 | 39 | 41 | Absent | ||
L CV (m/s) | 51 | 50 | 51 | 54 | 67 | 41 | 40 | Absent | ||
R Amp | 8.6 | 23 | 7.3 | 26 | 34 | 2.9 | 10.5 | Absent | ||
L Amp | 9.2 | 31 | 8.8 | 13 | 60 | 3.8 | 6.7 | Absent | ||
R F waves | 30.0-0.5 | 28.8-1.0 | 50.5-1.0 | 51.8-1.0 | ||||||
L F waves | 28.3-1.0 | 28.4-1.0 | 50.1-0.6 | 53.9-1.0 | ||||||
II-1 | R DL (ms) | 4.3 | 2.8 | 3.0 | 2.4 | 2.1 | Absent | 4.5 | Absent | 38.4 |
L DL (ms) | 4.1 | 3.0 | 2.8 | 2.5 | 2.0 | 4.9 | 5.1 | Absent | 37.5 | |
R CV (m/s) | 44 | 50 | 42 | 50 | 56 | Absent | 32 | Absent | ||
L CV (m/s) | 46 | 47 | 43 | 48 | 60 | 30 | 34 | Absent | ||
R Amp | 10.3 | 42 | 11.5 | 20 | 25 | Absent | 4.0 | Absent | ||
L Amp | 11.7 | 47 | 9.9 | 29 | 32 | 2.4 | 2.6 | Absent | ||
R F waves | 32.6-1.0 | 32.1-1.0 | Absent | 70.6-0.6 | ||||||
L F waves | 30.4-0.9 | 30.4-1.0 | 79.2-0.2 | 75.7-0.9 | ||||||
II-2 | R DL (ms) | 4.0 | 2.5 | 2.8 | 2.0 | 1.7 | 4.4 | 3.4 | Absent | 31.9 |
L DL (ms) | 4.2 | 2.7 | 3.0 | 2.3 | 1.7 | 3.8 | 3.8 | Absent | 31.6 | |
R CV (m/s) | 52 | 56 | 58 | 60 | 71 | 39 | 41 | Absent | ||
L CV (m/s) | 52 | 52 | 50 | 53 | 71 | 43 | 39 | Absent | ||
R Amp | 8.5 | 29 | 6.6 | 38 | 16 | 3.2 | 4.7 | Absent | ||
L Amp | 7.4 | 50 | 6.7 | 40 | 29 | 4.7 | 2.0 | Absent | ||
R F waves | 29.8-1.0 | 30.4-0.8 | 54.2-0.3 | 53.3-1.0 | ||||||
L F waves | 29.6-1.0 | 31.6-0.9 | 50.9-0.8 | 56.5-0.9 |
Muscle biopsies
I-1 | I-2 | II-1 | II-2 | |
---|---|---|---|---|
Changes of mitochondria | ||||
subsacrolemmal accumulation | +++ | +++ | ++ | + |
change in size and shape | +++ | ++ | ++ | + |
increase in amount | +++ | ++ | ++ | + |
Changes of membranous system
| ||||
triads proliferation, swollen | - | ++ | + | - |
increased amount of sacroplasmic reticulum | + | ++++ | - | +++ |
laminated bodies | - | - | - | ++ |
membranous debris | +++ | ++ | ++ | ++ |
Increased amount of lipid droplets
| + | ++ | +++ | ++++ |
Increased amount of lipofuscin
| + | + | + | ++ |
Increased amount of glycogen
| ++ | ++ | + | ++ |
Quantitation of skin innervations
Results of autonomic testings (Table 4)
I-1 | I-2 | II-1 | II-2 | ||
---|---|---|---|---|---|
RRIV (%) (N > 15) | 3.53 | 15.7 | 24.2 | 25.4 | |
Head-up tilt test | NR | NR | NR | NR | |
BR sensitivity (msec/mmHg) | -1.9 | -1.4 | 2.3 | 0.7 | |
30:15 ratio (N > 1.03) | 1.03 | 0.95 | 1.11 | 1.37 | |
SSR | |||||
onset latency (ms) | R palm | 1320 | 1700 | 1440 | 1720 |
L palm | 1400 | 1700 | 1400 | 1770 | |
R sole | 2300 | 2280 | 2060 | 2280 | |
L sole | 2290 | 2280 | 2250 | 2280 | |
amplitude (μV) | R palm | 2652 | 1569 | 978 | 1314 |
L palm | 2198 | 921 | 869 | 1099 | |
R sole | 315 | 159 | 61 | 688 | |
L sole | 399 | 239 | 74 | 562 | |
Q-Sweat test | |||||
onset latency (seconds) | Forearm | 137 | 219 | 185 | 275 |
Proximal leg | 217 | 194 | 165 | 128 | |
Distal leg | 165 | 148 | 168 | 136 | |
Foot | 165 | 203 | 189 | 122 | |
total volume (μl) | Forearm | 0.150 | 0.298 | 0.015 | 0.450 |
Proximal leg | 0.134 | 0.063 | 0.199 | 1.283 | |
Distal leg | 0.183 | 0.108 | 0.294 | 1.409 | |
Foot | 0.029 | 0.095 | 0.030 | 0.700 | |
skin temperature (°C) | Forearm | 36.5 | 36.4 | 36.5 | 35.4 |
Proximal leg | 35 | 35.8 | 36.4 | 35.7 | |
Distal leg | 35.6 | 36.3 | 34.9 | 35.3 | |
Foot | 35.7 | 35.2 | 34.7 | 35.4 | |
room temperature (°C) | 23 | 21 | 21 | 21 | |
room humidity (%) | 56 | 57 | 58 | 58 |
Discussion
Peripheral Nerve Abnormality
Reference No/ year | Total case No/gene mutation/ age or range of age (y/r) | Described type of neuropathy | Nerve conduction study | Sural nerve biopsy | Muscle biopsy |
---|---|---|---|---|---|
[5]/ 1079 | 4/ND/12-27 | S-M pnp | D | ND | ND |
[6]/1979 | 1/ND/25 | ND | D | D | ND |
[7]/1984 | 4/ND/35-43 | S-M pnp | D | D | D |
[8]/1985 | 1/ND/50 | S-M pnp | D | D | ND |
[9]/1986 | 3/ND/14-30 | demyelinated S-M pnp | D | D | ND |
[10]/1987 | 1/ND/29 | S-M pnp | D | D | D |
[11]/1990 | 1/ND/30 | S-M pnp | D | D | ND |
[12]/1991 | 1/ND/22 | Axonal pnp | D | D | ND |
[13]/1992 | 10/ND/26-44 | Mixed S-M pnp (2) and demyelinating S-M pnp (8) | D | ND | ND |
[14]/1995 | 1/ND/34 | Mixed | D | ND | ND |
[15]/2000 | 10/Da/24-54 | Axonal pnp (5), mixed pnp (1), pnp (1) | D | D | D |
[16]/2007 | 1/Db/47 | Polyneuropathy | D | ND | ND |
[17]/2007 | 1/Dc/42 | S-M polyneuropathy | D | D | ND |