Evidence of genetic heterogeneity among the nondystrophic myotonias.

Recent in vitro electrophysiologic studies have demonstrated abnormal sodium channel gating in muscle from patients with Thomsen's disease and have called the chloride hypothesis into question. Abnormal sodium channel function, like myotonia, is a feature common to Thomsen's disease and several myotonias that are genetically linked to a chromosome-17q sodium channel locus. We present a pedigree segregating an allele for Thomsen's disease that is unlinked to this sodium channel locus, thus constituting evidence of genetic heterogeneity among the nondystrophic myotonias.

Childhood eosinophilic fasciitis--progression to linear scleroderma.

A 2-year 10-month old girl developed eosinophilic fasciitis that resolved within one year after the administration of prednisone. She was left with changes similar to chronic linear scleroderma. Our case illustrates that eosinophilic fasciitis can occur in very young children and reinforces the hypothesis that it may be an early manifestation of scleroderma.

Identification of minimal expression of myotonic dystrophy using electroretinography.

The electroretinograms (ERGs) of patients with definite myotonic dystrophy were studied as well as neurologically asymptomatic patients with minimal expression of myotonic dystrophy. Children in 4 families exhibited definite myotonic dystrophy when neither parent exhibited clinical or electromyographic signs of myotonic dystrophy. Myotonic dystrophy is dominantly inherited. We were able to identify the asymptomatic parent with the gene in these families. This study suggests that ERG testing, which includes scotopically balanced dim blue and red flashes, will identify some asymptomatic adults minimally expressing the gene for myotonic dystrophy.

Pentazocine abuse masquerading as familial myopathy.

A 58-year-old man and his two young adult children showed fixed abduction of the arms, mild proximal weakness, and muscle induration. The skin over the upper arms, buttocks, and thighs was sclerotic and contained numerous healed punctate ulcers. One patient required skin grafting because of large, active ulcers on both arms. The initial diagnosis was an obscure inherited disorder, but each patient eventually admitted chronic self-injection of pentazocine, which was suspected because of the characteristic clinical findings.

Emery-Dreifuss muscular dystrophy.

Emery-Dreifuss dystrophy, an X-linked disorder, is a recently recognized distinct neuromuscular disease with special pediatric implications. We describe three affected boys with the typical early contractures and weakness. Two patients are from a large kindred that includes older affected males and carrier females, both of whom had lethal cardiac disease by mid-adulthood. The atrial arrhythmias are treatable by pacemaker if the diagnosis is established beforehand.

The Robin sequence as a consequence of malformation, dysplasia, and neuromuscular syndromes.

The Robin sequence is a pathogenetically and etiologically heterogeneous conditions that can be an isolated defect or one feature of many different syndromes. The association of this pattern of malformation with neuromuscular conditions has been alluded to in the literature but not well documented. We report a family with a distinct neuromuscular condition that includes the Robin sequence and discuss the human syndromes and animal models in which the Robin sequence occurs.

Drug trial of superoxide dismutase in Duchenne's muscular dystrophy.

A multicenter, randomized, double-blind, placebo-controlled drug trial in Duchenne's muscular dystrophy, evaluating a superoxide dismutase in 51 ambulatory patients for 18 months was conducted. Fourteen aspects of muscle strength and five of functional ability, as well as serum creatine phosphokinase (CPK) level were studied. The total change in strength, function, and CPK level did not differ significantly in the two groups. The testing method used was reliable in assessing the natural history of Duchenne's dystrophy and would, therefore, be useful in future multicenter drug trials.

Childhood chronic relapsing polyneuropathy: dramatic improvement following plasmapheresis.

We present clinical data on two boys with chronic relapsing polyneuropathy. Their recurrent episodes of weakness had produced marked disability which was unresponsive to continuous prednisone therapy. Plasmapheresis produced dramatic improvement in muscle strength and functional ability. The remissions induced have been sustained despite withdrawal of steroid therapy.

An aberrant adenylate kinase isoenzyme from the serum of patients with Duchenne muscular dystrophy.

The sera from patients with human Duchenne (X-linked) progressive muscular dystrophy contain elevated adenylate kinase (ATP: AMP phosphotransferase, EC 2.7.4.3) activities, in addition to their characteristically high creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) activities. By agarose gel electrophoresis of human Duchenne dystrophic serum, the presence of an apparently normal human serum adenylate kinase together with a variant species of adenylate kinase was detected. The latter enzyme species appeared, in its mobility, to be similar to that of the normal human liver-type adenylate kinase. The presence of this aberrant liver-type adenylate kinase could also be demonstrated by characteristic (for the liver type) inhibition patterns with P1,P5-di-(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate. On the other hand, by inhibition titrations with an anti-muscle-type adenylate kinase, hemolysates from the erythrocytes of several Duchenne and Becker's dystrophics were found to contain approx. 96% muscle-type adenylate kinase and their serum approx. 97% muscle-type adenylate kinase. These same patients contained approx. 89% M-M type creatine kinase in their serum (by inhibition against anti-human muscle-type creatine kinase) indicative of the presence also of M-B plus B-B type active isoenzymes. All of these data can best be explained by the presence of a variant or mutant adenylate kinase isoenzyme in the dystrophic serum. This isoenzyme appears to resemble the liver type in its inhibition patterns with P1,P5-di(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate, and in its heat stability (compare also the agarose gel electrophoresis pattern); but structurally, it is a muscle type, or derived from a muscle type, as shown immunologically by inhibition reactions with anti-muscle-type adenylate kinase. Whether this is a fetal-type isoenzyme of adenylate kinase will require further investigation.

Loss of strength and functional decline in Duchenne's dystrophy.

Clinical tests of strength and function were performed on 27 ambulatory patients with Duchenne's dystrophy every three months for 2 1/2 years. Linear decline of strength remains a fundamental characteristic of Duchenne's dystrophy. Although generally considered a homogeneous disease, our patients showed a broad spectrum of disability. Current tests of functional ability are poor measures of disease progression during most of the ambulatory period, since efficiency is maintained despite continuous decline in muscle strength. However, after this "latent" phase, failure of certain functions paralleled muscle deterioration closely, since task loss occurred within a narrow range of composite muscle strength. Finally, data on changes in body weight showed that most patients were excessively thin rather than obese. It is concluded that manual muscle strength testing remains the most valid method of monitoring disease progression and must be included in patient assessment.

Epidemiology of myelomeningocele in Utah.

This study suggests that in the Intermountain area of the United States (Utah, Wyoming, Idaho and Montana) there is an effect of social class on the incidence of myelomeningocele: the higher the social class the less the incidence. This survey also suggests that there is an influence from the social class in which the mother was raised, as well as that into which she marries. Birth order and maternal age were found to have no influence on the incidence of myelomeningocele in this study.

Abnormal leukocyte electrophoretic mobility in myotonic dystrophy.

Electrophoretic mobility of polymorphonuclear leukocytes (PMNs) was studied in 10 patients with myotonic dystrophy. The mobility of patients' PMNs differed significantly from that of controls. Following incubation with bacterial chemotactic factor the PMNs from patients showed significantly less change in net surface charge compared to that in controls. Our data support a leukocyte membrane defect in myotonic dystrophy.

The value of orthoses for patients with Duchenne muscular dystrophy.

We applied knee-ankle-foot orthoses to 17 consecutive patients with Duchenne muscular dystrophy at the time they lost independent ambulation. We judged the value of the orthoses solely by the patients' ability to walk. With the orthoses, 7 patients (41%) became effective ambulators and benefited greatly from the appliances. Four patients (23%) had borderline results. Six patients (35%) were considered failures because they achieved only braced standing. We believe orthoses are indicated for many but not all patients with Duchenne muscular dystropy.

Manual fluorometry of phenylalanine from blood specimens collected on filter paper: a modified procedure.

In this manual fluorometric method, blood samples are used that have been impregnated on the filter paper, a convenient collection technique that is widely used to screen newborns for phenylketonuria. The modified procedure, based on the method of McCaman and Robins [J. Lab Clin. Med. 59, 885 (1962)], includes elution of phenylalanine from specimens on filter paper, removal of proteins by precipitation with trichloroacetic acid at 0 degrees C, and then reaction with ninhydrin-peptide reagent for color development. The standard curve is linear to at least 200 mg/L and the CV is 6.3% for a phenylalanine concentration of 27 mg/L. The modified procedure is suitable both for early screening for phenylketonuria and for monitoring blood phenylalanine of phenylketonurics during dietary therapy.