Table 1.
Summary of Clinical Findings[Note]
|
Male Patients |
||||||||
| Affected |
Female Patients |
|||||||
| II-5 | II-6 | II-7 | II-8 | II-16 | II-11(Unaffected) | II-12 | II-13 | |
| Age at examination (years) | 66 | 53 | 62 | 15 | 35 | 56 | 37 | 39 |
| Height (cm) [percentile] | 167.5 [10] | 162.5 [3] | 162.5 [3] | 162.5 [25] | NA | 175.5 [50] | NA | NA |
| Head circumference (cm) [percentile] | 55 [30] | 56.5 [60] | 54.5 [25] | 53.5 [25] | 55.3 [40] | 58.6 [90] | NA | NA |
| Ear length (cm) | 7.5 | 7.3 | 7.3 | NA | 6.3 | NA | NA | NA |
| Midface hypoplasia | + | + | + | NA | − | − | NA | NA |
| Stub thumb | + | + | + | NA | − | − | NA | NA |
| Hyperextensible joints | + | + | + | NA | − | − | NA | NA |
| Hypotonia | + | NA | + | NA | − | − | NA | NA |
| Gastrointestinal problem | + | + | + | − | + | − | 25 | NA |
| Seizures | + | + | + | + | + | − | − | − |
| Movement disorder | − | + | + | + | − | − | NA | NA |
| Speech problem | + | + | + | + | + | − | − | − |
| Behavior disturbance | + | + | + | + | + | − | + | − |
| Intelligence quotient | 16 | 4 | 4 | NA | 9 | NA | 69 | 67 |
| Urine creatine:creatinine ratioa | 2.5 | NA | 1.7 | NA | NA | .4 | NA | NA |
| Creatine uptakeb (pmol creatine/μg protein) | 6.2 | ND | 6.9 | ND | ND | ND | ND | ND |
Note.— NA = not available; ND = not determined.
Urinary creatine was measured using capillary electrophoresis as described by Clark et al. (2001). A Beckman Pace MDQ capillary electrophoresis system was utilized for electrophoresis, and creatinine and creatine were monitored using a UV detector. Peak heights and migration times were calculated using Beckman software on an IBM 486 computer. A 50-mM phosphate buffer at pH 5.5 was used as the run buffer. The urine-dilution buffer consisted of the run buffer supplemented with 2% EDTA. The 0.020-mm capillary was 50 cm long (J&W Scientific). Each run included a 3-min wash with 1N NaOH followed by a 1-min wash with distilled water and a 3-min wash with run buffer. Each sample was injected for 5 s (20 psi) and was electrophoresed for 8 min at 25 kV. Absorbance was monitored at 214 nm. Urine was diluted 1:1 with the urine-dilution buffer and was electrophoresed. A set of standards for both creatine and creatinine were loaded with each sample run. Known concentrations were 0.5 mM, 1 mM, 2.5 mM, 5 mM, 7.5 mM, and 10 mM. For each sample, the concentration of both creatine and creatinine were calculated using standard curves derived from the set of standards. The creatine:creatinine ratio was calculated for both affected patients and the unaffected brother and control subjects.
Creatine uptake in fibroblasts was measured after a 24-h incubation in 500 mM creatine as described elsewhere (Salomons et al. 2001). The average uptake levels in two controls was 15.8 pmol creatine/μg protein.