Search

• Of 52 patients fulfilling the criteria of chronic inflammatory demyelinating polyneuropathy, 20 (38%) did not improve after intravenous immunoglobulin treatment, two (4%) had a short-lasting improvement and subsequent infusions had no effect, nine (17%) reached a spontaneously or therapeutically induced complete remission, and 21 patients (40%) needed intermittent infusions to maintain improvement. All patients who improved initially had symptoms that significantly interfered with life-style. After treatment, 90% of these patients were independent in their daily activities. Significantly associated with improvement were disease duration of less than 1 year, progression of weakness until treatment, absence of discrepancy in weakness between arms and legs, areflexia of the arms, and slowed nerve conduction velocity of the motor median nerve. The probability of improvement if all these features are present is 93%.

We report clinical and morphological data on seven patients with a congenital myopathy as well as data concerning five parents. Classical myopathies such as rod disease, centronuclear myopathy or central core disease could be ruled out. Structural abnormalities of intracellular organelles or particulate inclusions were rare and insignificant. The most prominent and constant features were minicores and focal loss of cross striations, associated with a prevalence of type 1 fibres, increasing with the age at time of biopsy. A carrier state could not be defined in the five examined parents neither on clinical nor on morphological grounds. Although our group of patients could not clinically be distinguished from other congenital myopathies, the combination of the lesions allow their individualization as a subgroup of multicore or minicore disease under the alreay proposed denomination of pleocore disease [Martin and Busch, abstract in Zentralbl Allg Pathol 124:156 (1980)]

Mutations causing Duchenne muscular dystrophy (DMD) have a short survival. Therefore, birth and population prevalence are maintained by new mutations. The present inventory was made to estimate the birth and population prevalence rates of DMD in the Netherlands. Seven methods of case identification were used. Data on 496 definite, probable or possible DMD patients born since 1961, or alive on January 1, 1983, were obtained. Several methods gave an estimated ascertainment of more than 95%. The prevalence rate at birth of DMD was estimated at 23.7×10-5 (1:4215) male live births (MLB) yearly. The prevalence rate in the male population on January 1, 1983 was 5.4×10-5 (1:18496). About 1% of the males in this study may have autosomal recessive Duchenne-like muscular dystrophy. Until now there has been no convincing evidence for geographic differences in DMD prevalence at birth. A list of frequency studies of Duchenne muscular dystrophy is included. The DMD mutation rate calculated by the indirect method is 7.9×10-5 genes per generation. However, this may well be an over-estimate, as this method does not account for germline mosaicism. Using a modified sex ratio method the proportion of sporadic DMD among all cases was estimated to be 0.106 (range 0–0.332). High frequency of germline mosaicism in DMD is a likely cause for the apparent lack of sporadic cases as found in previous studies, if mutation rates in male and female gametes are equal. Therefore, methods for estimating the proportion of new mutants in DMD should take germline mosaicism into account. The modified sex ratio method allows incorporation of data on germline mosaicism if available.

Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid a-glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral a-glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a “high-uptake” form of acid a-glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.

We studied a patient with the diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) for mitochondrial DNA mutations in muscle. Established MELAS mutations were excluded. Mitochondrial DNA was further analyzed for mutations in the 22 tRNA genes by single-strand conformation polymorphism (SSCP) analysis; a tRNAValmutation (G1642A) was found. The structure of the altered tRNA, the heteroplasmy, and the absence of the mutation in the mother and in 100 control subjects suggests that the tRNAValmutation is associated with the MELAS syndrome.

A case of muscle glycogen storage disease with the glycogen located in the cytosol is described. A variant a-glucosidase has been demonstrated in this patient but the cause of the metabolic disorder is still unclear.