Abstract
Sirs: Aceruloplasminemia is a rare neurodegenerative disease which is caused by homozygous mutations in the ceruloplasmin gene [8]. Apart from cerebellar and extrapyramidal movement disorders as well as dementia, affected patients have also presented with adultonset diabetes mellitus and retinal degeneration. Patients with heterozygous mutations in the ceruloplasmin gene are usually healthy. Recently, however, a few cases have been reported in which characteristic symptoms of aceruloplasminemia were found in association with heterozygous mutations in the ceruloplasmin gene [1, 2, 7]. The present report deals with a new case of this association. A previously healthy 16-year-old girl presented with a subacute, progressive primarily right-sided disorder of coordination and precision movements. The parents described a change in personality as well as an increased need for sleep. On examination she was found to have an oculomotor disorder with hypometric horizontal saccades and an abduction deficit on both sides. However, there was no evidence of Kayser-Fleischer rings or retinal degeneration. Dysdiadochokinesia and dysmetria were found, resulting in poor penmanship. Her gait was affected by involuntary movement of the right leg. Muscle tone was normal. There was abnormal limb drift on holding the outstretched upper and lower limbs as well as hyperkinesia of the right lower limb. MRI of brain and spinal cord were normal. The F-18-deoxyglucose-PET of the brain showed bilateral pathologically reduced glucose metabolism in the putamen, globus pallidus, caudate nucleus and posterior aspects of the thalamus (Fig. 1a, b). The EEG showed an intermittent left-sided parietal focus. Most laboratory results in the serum and cerebrospinal fluid were normal e. g. iron, transferrin, ferritin, liver enzymes, HIV-Testing, Vitamin B12, glucose tolerance test, ANA, ANCA, GM1-, GD1A,B-, Hu-antibodies, Antistreptolysin, Antistreptodornase, Gliadin-IgA-antibodies, oligoclonal banding and antibodies for borreliosis. Because of lowered serum copper (49μg/dl) as well as ceruloplasmin (10 mg/dl, normal range 20–60 mg/dl) and elevated “free” copper (~18μg/dl) Wilson’s disease was initially assumed. However, the point mutation (H1069Q of ATP7B gene) commonly found in Wilson’s disease was excluded. A six-week therapeutic trial with D-Pencillamine was unsuccessful. Finally, radio-copper testing as well as normal liver copper content in a biopsy specimen and normal urine copper values eliminated Wilson’s disease as being causative. Pantothenate kinase-associated neurodegeneration was also moleculargenetically excluded. Iron content in a liver biopsy specimen exceeded the normal expected range at 448 μg/g liver tissue. Serum ferroxidase activity was lowered (48.1 U/l, normal range 70–140 U/l; measured as described previously [13]). The molecular genetic analyses of ceruloplasmin gene, according to a PCR-based method [6], showed heterozygous mutation at the nucleotide position 2158. The usually conservative cytosine was replaced by thymine (C2158T), resulting in a missense mutation (Arg to Try) (Fig. 2). This heterozygous mutation was also found in the asympLETTER TO THE EDITORS
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