[Striatal uptake of I-123-beta-CIT and I-123-IBZM in patients with extrapyramidal symptoms]. / Striatale Aufnahme von I-123-beta-CIT und I-123-IBZM bei Patienten mit extrapyramidaler Symptomatik.

AIM: This pilot study deals with the question whether characteristic changes in local cerebral dopamine transporter function and D2-receptor binding capacity can be shown with SPET in idiopathic Parkinson syndrome (IPS) and secondary Parkinson syndrome (SPS). METHODS: In 16 patients (6 with IPS, 6 with SPS except Wilson's disease, and 4 with Wilson's disease) SPET studies were performed using I-123-beta-CIT and I-123-IBZM and a dual-head gamma camera. Images were obtained 20-24 h and 2 h post injection, respectively. For semiquantitative analysis count density ratios of basal ganglia (BG) and cerebellum (CER) were determined for I-123-beta-CIT and ratios between BG and medial frontal cortex (MFC) for I-123-IBZM. RESULTS: The BG/CER ratio in the I-123-beta-CIT studies averaged 3.04 +/- 0.83 in IPS and 7.73 +/- 3.28 in SPS (p < 0.01) (except Wilson's disease). In patients with IPS, the BG/MFC I-123-IBZM ratios of basal ganglia contralateral to the symptomatic side exceeded that of the individual ipsilateral BGs (1.75 +/- 0.12 vs. 1.61 +/- 0.16); these ratios were significantly reduced when compared with those of SPS patients, although the differences were less pronounced than those of I-123-beta-CIT uptake values. In some of the patients with Wilson's disease the BG/MFC ratio for I-123-IBZM was dramatically reduced (as low as 1.29), whereas I-123-beta-CIT uptake was only slightly reduced when compared with that of SPS patients (8.00 +/- 2.90, p < 0.01). CONCLUSION: It is concluded that the neurochemical changes that can be anticipated in the above diseases can be monitored with SPET. I-123-beta-CIT, however, appears to be more adequate to differentiate IPS from SPS than I-123-IBZM.

Three familial cases presenting with an immobile spine. Rigid spine or Emery-Dreifuss syndrome?

A father and his two sons presented with slowly progressive muscular weakness, contractures of the spine, elbows and ankles, and cardiac conduction disturbances in the father. Clinical and histological findings are discussed in relation to the hitherto reported cases of autosomal dominant variant of the Emery-Dreifuss syndrome and the distinction from the rigid spine syndrome.

Predictive testing for Wilson's disease using tightly linked and flanking DNA markers.

We studied DNA polymorphisms for five new chromosome 13 markers in 52 Wilson's disease (WD) families from Europe, North America, and the Middle East. There was significant evidence for linkage between the Wilson's disease locus (WND) and all the marker loci. Multilocus linkage analysis, using a genetic linkage map established from reference pedigrees, suggested that WND is most likely between D13S31 and D13S59, at distances of 0.4 and 1.2 centimorgans, respectively. Our results suggest that the chromosomal location of the Wilson's disease gene is the same in all families from the populations studied. This evidence and the availability of many close, flanking, and polymorphic DNA markers make possible accurate and informative testing of potential carriers and WD homozygotes in families with at least one previously affected child. An advantage of a genetic linkage test over other laboratory methods for prediction of genotype in WD is that a reliable diagnosis can be made at a much earlier stage in life, including prenatally. In addition, DNA testing can be used in place of an invasive liver biopsy procedure to confirm a diagnosis in patients with borderline serum ceruloplasmin levels. Presymptomatic identification will also allow therapeutic intervention to prevent symptoms before irreparable liver or neurologic damage occurs. We describe the implementation of prenatal and preclinical diagnosis for two families with WD.

Mode of action of triethylenetetramine dihydrochloride on copper metabolism in Wilson's disease.

The drug of choice for the initial treatment of "decoppering" in Wilson's disease, an inherited disorder of copper metabolism, is the chelating agent D-penicillamine. In the case of harmful side-effects an alternative drug is triethylenetetramine dihydrocholoride (trien or trientine). Using the 24-h-urine excretion of copper and the oral copper loading test with copper-64, a double function for trien was found: trien increases the urine copper excretion and decreases the intestinal copper absorption respectively.

[Wilson's disease in East Germany: in retrospect and perspectives -- an evaluation]. / Wilsonsche Erkrankung in der DDR: Rückblick und Ausblick--eine Bilanz.

Wilson's disease is an autosomal recessive inherited metabolic disorder due to a disturbance of copper metabolism. Although the primary genetic defect is not known a longlife treatment is necessary for establishing a negative copper balance by removing the metal of the abnormal body stores. Experiences in handling with this disease in our country over a period of 20 years are reported. Especially epidemiologic findings, the diagnostic procedures and the strategies in therapeutic regimes are discussed. Future advances in genomic diagnostics are mentioned.

[Nosologic evaluation of oculopharyngeal myopathic syndromes]. / Nosologischer Stellenwert okulopharyngealer myopathischer Syndrome.

Three patients with oculopharyngeal involvement of neuromuscular origin are presented: one patient suffering from an oculopharyngeal neuromuscular disease (developing an oculopharyngeal muscular dystrophy?) and two patients representing a neuromuscular mitochondriopathy. There is no evidence that the oculopharyngeal myopathy and neuromuscular disease, respectively, are the same, despite the simularity of the syndrome. The different clinico-pathological types of oculopharyngeal syndromes are discussed. Following-up the development of further manifestations of the oculopharyngeal syndrome can helf classifying them.

[Secondary muscular carnitine deficiency following immunosuppressive treatment]. / Sekundärer muskulärer Carnitinmangel nach immunsuppressiver Behandlung.

Carnitine deficiency syndromes can be classified into two groups: primary carnitine deficiency and secondary carnitine deficiency syndromes. A lipid storage myopathy with carnitine deficiency following an immunosuppressive therapy is described in a young man suffering from a possible polymyositis. After treatment with L-carnitine both biochemical and morphological features recovered. A secondary carnitine deficiency syndrome due to an immunosuppressive therapy is supposed.

[The carnitine level of the umbilical cord blood in relation to the course of labor]. / Der Carnitinspiegel des Nabelschnurblutes in Abhängigkeit vom Geburtsverlauf.

Total and free carnitine were analyzed in cord blood of 24 newborn babies, with uncomplicated delivery, and 12 neonates with protacted labour. At birth, the mean neonatal carnitine value (total 33.7 +/- 10.1; free 23.5 +/- 7.5 mumol/l) was lower than the mean adult value (60.0 +/- 10.0 and 50.5 +/- 7.3, resp.). The carnitine values in the group with protracted labour increase slowly with duration of delivery. In our opinion carnitine values of neonates are not suitable for diagnosis of systemic carnitine deficiency syndrome.

Long-term care and management of Wilson's disease in the GDR.

Diagnosis, long-term management and family investigations of Wilson's disease are provided by selected clinical institutions in the GDR. From 187 patients detected since 1949, 111 are alive. In spite of the principal effectiveness of penicillamine treatment, confirmed by the disappearance of most of the central nervous system symptoms and successful professional rehabilitation of many patients, insufficient therapeutic discipline, psychosocial disturbances and penicillamine side-effects forcing its substitution by zinc or triethylenetetramine dihydrochloride in 14 cases need our further attention.

Myopathy with mitochondrial abnormalities and rimmed vacuoles.

A man of 44 years suffering from an exercise-induced neuromuscular disease with mitochondrial abnormalities and rimmed vacuoles is reported. The mitochondrial abnormalities and rimmed vacuoles (autophagic vacuoles) are interpreted as sequential changes of the same pathogenetic process depending on the degree of energy deficiency.

The Kayser-Fleischer ring during long-term treatment in Wilson's disease (hepatolenticular degeneration). A follow-up study.

The role of Kayser-Fleischer rings is described in 67 patients with Wilson's disease, both in the asymptomatic and symptomatic stage of the disease during life-long therapy, which lasted up to 22 years. The rings were missing in 60% of patients in the presymptomatic stage and in 2% of those in the symptomatic stage at the time of diagnosis. The Kayser-Fleischer rings disappeared in 81% of the patients (completely in 41% and incompletely in 59%). In 2 of the 6 asymptomatic patients the rings did not reabsorb even after therapy of more than 10 years. The fading of Kayser-Fleischer rings seems to be independent not only of the stage of the disease but also of the effectiveness of the decopperizing treatment.

[Metabolic myopathies]. / Metabolische Myopathien.

Metabolic myopathies are a rare group of disorders. These myopathies reveal a varying severity of a proximal, distal or generalized muscular involvement indicating a progressive myopathy or recurrent episodes of weakness, pain, cramps and stiffness combined with exercise. Some important disorders and their biochemical defects are described. Particular attention is paid to helpful biochemical investigative methods.

[Detection, genetic counseling and phenotype prevention of Duchenne muscular dystrophy]. / Erfassung, genetische Beratung und Phänotypprophylaxe der Duchenneschen Muskeldystrophie.

Literature data and the own ascertainment of Duchenne muscular dystrophy cases concentrated on the Leipzig county confirm the necessity of early diagnosis and of central registration, search for female carries and genetic counselling. A newborn screening is supported provided that its organization will be practicable. About 12% of Duchenne cases are secondary affections of brothers. It should be possible to prevent one third of all cases by means of counselling also of the female relatives of the mothers. The repeated estimation of serum creatinkinase activity, completed by electromyography, has the greatest practical importance for the identification of heterozygous carriers. For the genetic counselling of definite carriers and women at risk it is possible only to recommend intrauterine sex prediction and the selective abortion of male fetuses.

[Acoustically evoked brain stem potential in Wilson disease]. / Akustisch evoziertes Hirnstammpotential bei der Wilsonschen Erkrankung.

By 48 patients with Wilson's disease the brainstem acoustic evoked potentials were stated. There were 35 pathological findings (73%), 13 were normal (27%). The waves, determined by the middle and upper brainstem (Pons and Mesencephalon) showed most of all pathological changes. Those patients with forms of Wilson's disease called Pseudoskelerose and Pseudoparkinson showed the most pathological findings. But one could watch these findings by about 30% of patients in preclinical stage. This method can possibly be used for early detection of disorders of brainstem functions and in the same way it can be used for control of treatment by patients in preclinical stage.