Diagnosis Of Duchenne Muscular Dystrophy Research Articles

False elevation of amniotic fluid enzymes of relevance for prenatal diagnosis: creatine kinase measurement in relation to Duchenne muscular dystrophy.

The creatine kinase activity of amniotic fluid was measured in samples collected at fetoscopy. In our first study, the control sample range was 0.25 IU/l, although four samples had activities of 35-85 IU/l. Elevated values did not correlate with the activities in the fetal or maternal circulations. Electrophoresis revealed the presence of the BB isozyme of creatine kinase rather than just the MM form as expected. This suggested that the source of the elevated enzyme activity was from the myometrium, damaged by insertion of the trocar and cannula. In a further series the first 2 ml of amniotic fluid withdrawn yielded a much higher creatine kinase activity than a second aliquot. A control series of such second samples (first 2 ml discarded) gave an activity range of 0-7 IU/l with no spuriously high values. This compares favourably with a series from single samplings taken by amniocentesis. Normal creatine kinase activities were found in the amniotic fluids from 20 pregnancies at risk of Duchenne muscular dystrophy. We conclude that for accurate measurement of amniotic fluid enzyme activity the first portion withdrawn should be discarded. Amniotic fluid creatine kinase activity is of no value for the prenatal diagnosis of Duchenne muscular dystrophy.

The stability of MM-creatine kinase activity in human fetal plasma — a pitfall in the prenatal diagnosis of Duchenne muscular dystrophy

The stability of MM-creatine kinase activity in human fetal plasma — a pitfall in the prenatal diagnosis of Duchenne muscular dystrophy

Diagnosis of Duchenne muscular dystrophy: experiences of parents of sufferers.

Sixty nine parents of boys suffering from Duchenne muscular dystrophy were interviewed at home. The interview explored the parents' experiences at the time of their son's diagnosis. Many families had experienced distressing delays (average 2.5 years) between the time they first became aware of symptoms and the time of the diagnosis. On only 18 occasions were both parents told of the diagnosis together. One third of the parents were "not satisfied" with the way the diagnosis had been communicated. Parents want to know as soon as possible if there is something wrong with their child. They should be told the diagnosis together and in private. Full information should be given and a series of contacts should be arranged.

Fetal muscle biopsy.

Fetal muscle specimens suitable for histological and histochemical studies were obtained under fetoscopic visualization by removing a small piece of skin, thereby exposing the underlying muscle. The procedure was carried out in 7 cases prior to second-trimester abortion. Muscle specimens so obtained may become useful in the prenatal diagnosis of Duchenne muscular dystrophy.

Pyruvate-kinase (PK) and creatine-kinase (CK) in normal pregnancy and its implication in genetic counseling of Duchenne muscular dystrophy (DMD).

The activities of pyruvate-kinase (PK) and creatine-kinase (CK) were measured in 50 normal pregnant women in both serum and amniotic fluid. Serum PK activity was found to be significantly higher in pregnant than in nonpregnant women, while serum CK did not differ significantly between the two population samples. In amniotic fluid, very little or no PK or CK activity was found. However, the mean PK activity in amniotic fluid obtained from women carrying male fetuses was significantly higher than in those carrying female fetuses. At the present time, it is concluded that if a woman at risk for having a son with Duchenne dystrophy is seeking genetic counseling when already pregnant her serum PK or CK should be compared with that of normal female pregnant controls. It is also suggested that determination of pyruvate-kinase in fetal blood might be used in addition to CK for prenatal diagnosis of Duchenne muscular dystrophy.

Prenatal diagnosis of duchenne muscular dystrophy: failure of amniotic fluid and maternal serum Nτ-methylhistidine analyses to detect affected fetuses

Nτ-Methylhistidine (MH) and creatinine levels were determined in amniotic fluid and maternal serum from 81 women undergoing midtrimester amniocentesis for reasons other than the diagnosis of neuromuscular disease. Samples were also examined in three pregnancies with male fetuses who were subsequently found to have Duchenne muscular dystrophy (DMD). Between 16 and 20 weeks' gestation, amniotic fluid and maternal serum MH levels averaged 3.22 and 1.94 μmoles/L, respectively. No significant differences were found between the control and affected fetuses for MH and creatinine levels or for MH/creatinine ratios from amniotic fluid or maternal serum. Determination of amniotic fluid MH level thus has no apparent value in the prenatal diagnosis of DMD.

Radioimmunoassay of human muscle carbonic anhydrase III in dystrophic states

A radioimmunoassay for the human isozyme carbonic anhydrase III (CAIII) has been developed. The assay can detect levels as low as 4μg/l of sample. Plasma CAIII levels in patients suffering from Duchenne muscular dystrophy were found to be up to 39 times greater than levels in a control group. Urine CAIII levels in patients suffering from Duchenne muscular dystrophy were not significantly different from the levels found in urine from normal adults. Measurement of plasma CAIII levels may be useful in prenatal diagnosis of Duchenne muscular dystrophy, and in investigation of adult skeletal muscle disease.

Serum levels of myoglobin and creatine kinase in Duchenne muscular dystrophy.

Using a sensitive myoglobin-radioimmunoassay (Mb-RIA) serum Mb was measured in 50 patients with Duchenne muscular dystrophy (DMD) and compared with the serum creatine kinase (CK) activities. The Mb concentrations (normal range 4-60 ng/ml) measured ranged between 160-6,000 ng/ml and did not only show a significant correlation to the CK but also an inverse relationship to the age of the patients. It is suggested that Mb is an essential adjunct in the diagnosis of DMD.

ANTENATAL DIAGNOSIS OF DUCHENNE MUSCULAR DYSTROPHY

As a means of assessing the value of fetal serum-creatine-kinase (S.C.K.) levels in the antenatal diagnosis of Duchenne muscular dystrophy (D.M.D.), fetal muscle from control and at-risk fetuses was studied histologically and the findings were related to fetal S.C.K. levels. Of 7 at-risk fetuses 4 were believed to have normal muscle and all these had normal S.C.K. levels. However, of 3 fetuses with abnormal muscle only 1 had a raised S.C.K. level. At present cau tion should be exercised in offering antenatal diagnosis in D.M.D. on the basis of fetal S.C.K. levels.

Erythrocyte membrane abnormalities in Duchenne muscular dystrophy monitored by saturation transfer electron paramagnetic resonance spectroscopy.

Saturation transfer electron paramagnetic resonance and the spin label 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl were used to study erythrocytes from patients with Duchenne muscular dystrophy or Becker syndrome and from age-matched normal boys. There were significant differences in the spectral intensities of erythrocytes from Duchenne patients when compared to controls. Spectral intensities increased with time in the former; no such change was observed in the latter. Saturation transfer electron paramagnetic resonance spectra of erythrocytes from patients with Becker syndrome were significantly different from those from Duchenne patients but were not significantly different from normals. These observations suggest the possible usefulness of these techniques in the differential diagnosis of Duchenne muscular dystrophy. Spin label concentration spectral studies suggest that the observed spectral differences between Duchenne patients and controls were due to differential spin exchange phenomena.

Impaired visual-motor ability of children with Duchenne muscular dystrophy.

14 of 21 boys from 6 to 13 yr. of age with a medical diagnosis of Duchenne muscular dystrophy obtained impaired scores on the Bender-Gestalt test indicative of mild to severe visual-motor disability. The Bender-Gestalt scores were associated with WISC Verbal, Performance, and Full Scale IQ scores at the .01 level.

Increased plasma enzyme concentrations in rats with functional ischaemia of muscle provide a possible model of Duchenne muscular dystrophy.

THE early and mid-stage histopathological lesions of Duchenne muscular dystrophy are highly characteristic1. The early lesions are focal groups of muscle fibres undergoing necrosis surrounded by a field of normal muscle fibres, while in the mid-stage lesions there is marked proliferation of endomysial connective tissue between muscle fibres that are small, enlarged and sometimes with internal nuclei. During these phases of the disease process, serum enzyme levels of creatine phosphokinase (CPK), glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) are markedly increased2,3. These increases are often used in the diagnosis of Duchenne dystrophy.