Patient no. | Age at diagnosis (year of birth) | Clinical symptoms | Brain imaging, autopsy | Complex IV activity (% citric synthase) | Citric synthase activity (nmol/min/g protein) | Presence of c.841delCT SURF1 mutation at both alleles*/ | |
1 | 2 years (1987) | 4 months: motor regression, floppiness, bulbar symptoms, hirsutism, lactic acidaemia | <3.0 | 70.4 | c.841delCT | + | |
2 | 7 years (1987) | 12 months: trembling, uncertain gait, myoclonic jerks, strabismus | MRI: hyperintensive signals at lenticular nuclei areas | 5.7 | 146 | c.841delCT | + |
3 | 12 years (1987) | 30 months: dystonic movements, failure to thrive | MRI: symmetric hyperintensive signals at lenticular and caudate nuclei, medulla oblongata putamen, globi pallidi | 3.5 | 224.6 | c.841delCT | + |
4 | 3.5 years (1989) | 5 months: failure to thrive, floppiness, nystagmus, irregular ventilation, trembling, hirsutism. LS diagnosed at autopsy of older brother | 9.6 | 311 | c.841delCT | c.841delCT | |
5 | 4 years (1989) | 12 months: failure to thrive, vomiting, irregular ventilation. Death at the age of 4 | CT: Symmetric hypodensive changes in basal ganglia | NA | NA | c.841delCT | c.841delCT |
6 | 6.5 years (1990) | 16 months: speech difficulties, hypotonia, nystagmus, motor regression. LS diagnosed at autopsy of sibling (see patient 11) | 7.4 | 86 | c.841delCT | + | |
7 | 3.75 years (1990) | 2 years: difficulty in walking and speaking, failure to thrive, strabismus, hirsutism, hyperventilation episodes; CT of older brother: hypodense areas at LS typical localisation | 8.4 | 121.7 | c.841delCT | c.841delCT | |
8 | 3 years (1990) | 12 months: failure to thrive, floppiness, hirsutism, irregular respiration. CT and autopsy of older sister revealed typical LS changes | NA | NA | c.841delCT | c.841delCT | |
9 | 3 years (1991) | 14 months: regression of motor skills, failure to thrive, hirsutism, tremor, eye movement dissociation, apneic bouts, death at the age of 2.5 years | <3.0 | 175 | c.841delCT | c.841delCT | |
10 | 2.5 years (1992) | 3 months: failure to thrive, hypotonia, hirsutism; MRI of younger affected brother: LS changes in basal ganglia | CT: hypodensic areas in both cerebellar hemispheres and caudate nuclei | <3.0 | 136 | c.841delCT | c.841delCT |
11 | 10 years (1993) | 16 months: nystagmus, speech and walking difficulties. Died at age of >10 years | At autopsy: spongiform lesions; vascular proliferation and neuronal loss in mesencephalon, diencephalon, medulla, and white matter of cerebellum | <3.0 | 104.1 | c.841delCT | + |
12 | 1.75 years (1994) | 9 months: hypotonia, floppiness, failure to thrive, vomiting, tremor | NA | NA | c.841delCT | c.841delCT | |
13 | 2 years (1995) | 19 months: tremor, eye movement dissociation, dystonia, irregular breathing | CT: Symmetric hypodense areas of basal ganglia | 6.2 | 194.9 | c.841delCT | c.841delCT |
14 | 3 years (1996) | 12 months; floppiness, irregular respiration, eye movement dissociation, strabismus, hirsutism | MRI at 2.5 years: symmetric hyperintensive signals in basal ganglia | 3.7 | 111.4 | c.841delCT | + |
15 | 2.75 years (1997) | 4 months: motor regression, failure to thrive, floppiness, tremor, hirsutism, lactic acidaemia | 5.3 | 112.7 | c.841delCT | c.841delCT | |
16 | 9 months (1997) | 2 months: floppiness, vomiting, irregular respiration, eye dissociation, ptosis, hirsutism. LS in older brother | MRI at 4 years: symmetric hyperintensive signals in basal ganglia, brain atrophy | 3.6 | 223 | c.841delCT | c.841delCT |
17 | 1.5 years (1997) | 7 months; failure to thrive, vomiting, hypotonia, hirsutism, strabismus, lactic acidaemia | 5.8 | 174 | c.841delCT | c.841delCT | |
18 | 1.5 years (1998) | 14 months: motor regression, trembling, hirsutism, hypotonia | MRI: symmetric hyperintensive signals in basal ganglia | 4.3 | 133.2 | c.841delCT | c.841delCT |
19 | 1.5 years (2000) | 7 months: motor regression, irregular respiration, vomiting | MRI: symmetric hyperintensive signals in basal ganglia | <3.0 | 296.6 | c.841delCT | c.841delCT |
20 | 1 year (2000) | In infancy: failure to thrive, vomiting, tremor, irregular ventilation, lactic acidaemia. Prolonged artificial ventilation before death | Autopsy at 4 years: Massive encephalomalacia obscurring topography of possible lesions. Severe mixed liver steatosis (90%); numerous lipid vacuoles in proximal convoloted renal tubules | <3.0 | 104.1 | c.841delCT | + |
21 | 1.5 years (2002) | 6 months: failure to thrive, hypotonia, hyperventilation episodes, lactic acidaemia | MRI: symmetric hyperintensive signals at lenticular nuclei, putamen, crura cerebri, substantia nigra, cerebellum periventricular areas, medulla oblongata. | <3.0 | 209.7 | c.841delCT | c.841delCT |
Average (mean (SD)) | 4.7 (2.1) | 175.7 (38.2) | |||||
Reference (18 cases; mean (SD)) | 26.4 (7.4) | 123.0 (26.0) |
CT, computer tomography; MRI, magnetic resonance imaging; NA, not analysed; +, presence of non-c.841delCT mutations.13 27 36