Congenital myasthenic syndromes in two kinships with end-plate acetylcholine receptor and utrophin deficiency.

We studied two families with five affected members suffering from ptosis and slowly progressive limb-girdle muscle weakness. All patients had abnormal decremental response on low-frequency nerve stimulation, but there were no repetitive responses to single stimuli. The patients improved on anti-acetylcholinesterase drugs. Intercostal muscle was obtained for special studies from one patient of each family. In vitro microelectrode studies were done in Patient 1. Miniature end-plate potentials were of low amplitude, and the quantal content of the evoked end-plate potentials was normal. Light microscopy revealed a marked type 1 fiber predominance. Acetylcholinesterase reactivity was dispersed over increased length of individual fibers in Patient 2. On morphometry of the end-plate ultrastructure, the number of secondary synaptic clefts per neuromuscular junction and the expansion of the postsynaptic area were markedly reduced. In Patient 1, but not in Patient 2, the envelopment of the nerve terminal by Schwann cell was increased. Acetylcholine-receptor (AChR) density was reduced as judged by the reduced immunoreactivity to antibodies against different receptor subunits. Immunohistochemical analysis of proteins known to be involved in orchestrating the end-plate structure showed deficiency of the AChR-associated protein utrophin. These patients appear to have a defect in the development or maintenance of the postsynaptic clefts; whether this defect results from or causes a reduced expression of utrophin or AChR is unclear.

Comparative morphometry of myelinated nerve fibres in the normal and pathologically altered human sural and tibial nerve.

To assess neuropathological changes in human nerves, biopsies are usually performed on the sural nerve or other nerves supplying only a small area of skin. It is not yet clearly understood to what extent the changes found in this sensory nerve correspond to the changes found in other distal sensomotory nerves. To answer this question, we made a comparative morphometric analysis of the sural and tibial nerve. In 39 autopsy cases (aged 22 - 90 years) the sural and the tibial nerve were subject of image analysis. The histological picture in this study group was clearly influenced by neuropathological changes as well as age-related changes. For each morphometric parameter in the sural and tibial nerve, we evaluated Pearson's correlation. The highest coefficient of correlation (r) was seen in those parameters that represented the condition of the myelin sheath area: the density of nerve fibre area (sum of measured nerve, fibre areas/analyzed endoneural area) (r = 0.86) and the density of myelin sheath area (sum of measured myelin areas/analyzed endoneural area) (r = 0.86). Similar correlations were obtained for the mean of axon diameter (r = 0.82), the numerical density of nerve fibre count (nerve fibre count/analyzed endoneural area) (r = 0.77), the mean of nerve fibre diameter (r = 0.77) and the mean of myelin sheath thickness (r = 0.72). Our results revealed a good or very good statistical correlation of morphometric parameters between the two examined nerves. They support the assumption that the sural nerve sufficiently reflects the histological changes in other distal sensomotoric nerves. This is valid at least in systemic neuropathological diseases and age-dependent processes.

[A patient with mixed collagen disease, antiphospholipid syndrome and Sjögren syndrome]. / Eine Patientin mit Mischkollagenose, Antiphospholipid-Syndrom und Sjögren-Syndrom.

CASE REPORT: A 32-year-old female patient is described who suffered from common symptoms such as Raynaud's phenomenon and swollen fingers, high titers of antibodies to U1RNP, SLE-like findings, scleroderma-like findings and polymyositis-like findings. A diagnosis of mixed connective tissue disease (Sharp-syndrome) was established. In addition, the patient had antibodies against cardiolipin, thrombocytopenia, recurrent fetal loss and a history of deep venous thrombosis of her left leg which is typical for an antiphospholipid syndrome. The symptoms dry eyes and dry mouth pointed at secondary Sjögren's syndrome. The diagnosis of these disease entities and the therapeutic regimens are described and discussed.

[Generalized myoclonus as the only symptom of neurosyphilis]. / Generalisierte Myoklonien als alleiniges Symptom einer Neurosyphilis.

Symptomatic myoclonus syndromes can be caused by a broad range of etiological factors. We report the case of a 40-year-old woman who showed spontaneous and continuous myoclonus with predominance distally and in the arms as the only neurological symptom. CSF evaluation revealed acute neurosyphilis. Six months after antibiotic treatment, the movement disorder had disappeared.

[Clinical aspects of ataxia teleangiectatica (Louis-Bar syndrome)]. / Zur Klinik der Ataxia teleangiectatica (Louis-Bar-Syndrom).

BACKGROUND: Ataxia telangiectasia is an autosomal recessive inherited multisystem disease of childhood characterized by progressive cerebellar ataxia, oculo-cutaneous telangiectasia, immunological defects with increased susceptibility to infection and malignant neoplasms. PATIENT: A 20-year-old patient with ataxia telangiectasia (Louis-Bar syndrome), demonstrating the typical features of this hereditary disease, is described. The ophthalmological findings showed telangiectasia of the horizontal conjunctival vessels in the exposed bulbar conjunctivae and oculomotor signs with pathological pursuit and command movements, dissociated nystagmus, failure of gaze holding and convergence. RESULTS: The ataxia is the first symptom and becomes apparent when the child starts to walk. The pathognomonic telangiectasia at the light-exposed areas of the bulbar conjunctiva point the way to the diagnosis. There is no specific treatment for this disease. CONCLUSIONS: The ophthalmologist is able to confirm the clinical diagnosis by demonstrating the telangiectasia. Due to the increased disposition to malignant neoplasms regular check-ups should be performed.

Mutation analysis in myophosphorylase deficiency (McArdle's disease).

Inherited deficiency of myophosphorylase leads to glycogen storage disease type V (McArdle's disease). We performed mutation analysis in 9 patients of eight unrelated families from Germany with typical clinical presentation of myophosphorylase deficiency. Beside previously described mutations we identified four novel mutations in the myophosphorylase gene. Four patients were homozygous for a nonsense mutation Arg49Stop that has been reported to be the most common mutation in white patients. Two affected siblings were compound heterozygotes for a novel missense mutation Gly685Arg and the nonsense mutation Arg49Stop. One patient carried a novel nonsense mutation Arg575Stop and a previously identified missense mutation Gly204Ser. In another patient, we identified a novel missense mutation Gln665Glu and a single-base deletion delA in Lys753. One patient of Turkish ancestry carried a newly identified homozygous A-to-G transition (ATG to GTG) abolishing the translation initiation codon of the myophosphorylase gene. These results suggest that Arg49Stop also is the most common genetic error associated with myophosphorylase deficiency in the German population. Our findings further demonstrate molecular heterogeneity of myophosphorylase deficiency among the clinically homogeneous patients we studied.