Peroneal muscular atrophy with Poland syndrome

A 22-year-old male college student had a syndactyly between the second and third fingers of his left hand, which was congenitally small in size. His left pectoralis muscles were absent. He first walked at the age of 12 months, but soon developed difficulties in walking due to weakness of the legs. Atrophy and weakness of the legs aggravated gradually. He was diagnosed as having peroneal muscular atrophy and Poland syndrome, an association of which has not been reported before. A small number of similar cases of peroneal muscular atrophy with various skeletal abnormalities in the literature suggest that the association is not incidental, but of clinical significance.     

Charcot-Marie-Tooth disease in northern Sweden: an epidemilogical and clinical study

One hundred four cases of Charcot-Marie-Tooth desease (CMT) in 52 families were identified within a defined area in northern Sweden corresponding to a prevalence rate of 20.1 cases per 100000. The distribution of cases was not uniform. The prevalence rate is compared with previous prevalences studies focusing on Charcot-Marie-Tooth disease or hereditary motor and sensory neurophaty (HMSN). Three patients were classified as the distal spinal muscular atrophy type of CMT and one patient was not possible to classfiy. For seventy-five patients, available to clinical examination within the study, data were collected as to age to onset, symnptoms, clinical findigs and degree of disability.     

Peroneal muscular atrophy. Part 2. Nerve biopsy studies

The present study used the nerve pathology, studied by quantitative light microscopy, as the sole basis for classification of peroneal muscular atrophy (PMA). The findings in biopsies of superficial peroneal nerves of 20 patients were compared with normal values obtained from 8 controls. Three homogeneous groups comprising 17 out of 20 patients were clearly identified. The hypertrophic type (7 cases) was characterized by (1) many multilamellated onion bulb formations; (2) extensive loss of MF with both involvement of the largest and smallest fibers; (3) lack of significant cluster formation. The neuronal sensori-motor type (5 cases) was characterized by (1) absence of any OB; (2) elective loss of large MF; (3) abundance of clusters with significant increase of the small MF population. The neuronal motor type (5 cases) showed a virtually normal sensory nerve except for fairly numerous clusters in some cases. Comparing this classification based on histomorphometric grounds, with the electrophysiological data it appears that 14 patients out of 17 would be correctly classified as hypertrophic or neuronal with respect to the motor nerve conduction velocity of the median nerve alone. Three cases were not classified in the previous groups since they differed notably in one or more parameters from the typical cases. A possible intermediate group is discussed.     

Analysis of spinal muscular atrophy-like patients by targeted resequencing

BackgroundSeveral effective therapies have been developed for spinal muscular atrophy (SMA), but there are multiple diseases that show SMA-like symptoms, necessitating efficient differential genetic diagnostic methods. Advancements in next-generation sequencing (NGS) technology have facilitated the successful diagnosis of many undiagnosed genetic diseases. Here, we applied NGS along with conventional methods for the molecular diagnosis of undiagnosed patients with lower motor neuron (LMN) symptoms who were initially suspected to have SMA.MethodsWe enrolled 157 patients with LMN symptoms who visited the Institute of Medical Genetics, Tokyo Women’s Medical University, between 2005 and 2016. We excluded 86 patients diagnosed with SMA after confirming the causative SMN1 gene deletion or variants. Finally, we examined 12 undiagnosed patients from eight families by targeted resequencing using NGS. Variants were selected on the basis of literature search and databases, and mutations in a gene where loss of function is a known mechanism of disease were considered as pathogenic. Candidate variants were validated by Sanger sequencing.ResultsWe detected novel variants for three patients from two families. Patients 1 and 2 (siblings) showed compound heterozygous TTN variants (c.6621delG, p.W2207Cfs*28 and c.23718T>A, p.F7906L), while patient 3 displayed compound heterozygous KIF1A variants of (c.3871C>T, p.R1291C and c.3898G>A, p.V1300M).ConclusionsWe detected appropriate variants using our approach of obtaining candidate pathogenic variants by targeted resequencing through NGS and narrowed down the variants in light of patient clinical symptoms. We successfully identified novel causative variants in three undiagnosed patients, which indicated the effectiveness of our approach.     

AAEM minimonograph #46: Neurogenic muscle hypertrophy

Muscle hypertrophy occurs uncommonly in several neurogenic disorders including neuropathies, radiculopathies, spinal muscular atrophy, and post-polio syndrome. Its pathogenesis varies in different circumstances. In the presence of generalized myokymia and neuromyotonia (Isaacs' syndrome), symmetrical hypertrophy appears to be the result of continuous spontaneous electrical stimulation of myofibers and, in some cases, results in type 1 myofiber preponderance. Focal hypertrophy occurring with radiculopathies and mononeuropathies was associated with complex repetitive discharges (CRDs) in approximately half the cases. CRDs may play a role in the pathogenesis of myofiber hypertrophy by continuous myofiber stimulation, but in some cases, with and without CRDs, myofiber hypertrophy may be related to mechanical events. Muscle enlargement seen in old polio appears to involve a significant degree of pseudohypertrophy, although some myofiber hypertrophy occurs. The symmetrical occurrence of hypertrophy in genetically determined disorders, such as spinal muscular atrophy, and hereditary motor and sensory neuropathy types 1 and 2 may have both a genetic and a mechanical basis in addition to pseudohypertrophy in some cases. © 1996 American Association of Electrodiagnostic Medicine. Published by John Wiley & Sons, Inc.     

Neurotrophic regulation of rat muscle glucose-6-phosphate dehydrogenase in vitro

In organ culture of rat diaphragm, the presence of a 2–2.5 cm phrenic nerve stump delays the time of failure of miniature endplate potentials and eliminates the increase in glucose-6-phosphate dehydrogenase (G6PD) activity which otherwise occurs at 16.5 h in muscles cultured without nerve stumps. The nerve stump effect persists in the presence of blocking doses ofd-tubocurarine but is eliminated by nerve crush. As shown by studies of amino acid incorporation into protein, the effect does not involve an overall change in protein synthesis. Effluents collected over 1–2 h from unstimulated or stimulated phrenic nerve-muscle preparations had no effect on G6PD activity when applied to muscles cultured without nerve stumps. However, medium conditioned by use in organ cultures with long nerve stumps partially countered the denervation-like effect in host cultures. Thus, the nerve maintains muscle G6PD by a humoral mechanism probably unrelated to impulse activity or nicotinic receptor activation.     

Zur Differentialdiagnose der scapulo-peronealen Amyotrophie

Zusammenfassung Es wird über ein scapulo-peroneales Syndrom berichtet, dessen regellose, schubweise Entwicklung über Jahre von Schmerzen, distal betonten Paraesthesien sowie Hypaesthesien im Bereich der Hände und Unterschenkel begleitet wurde. Asymmetrische Paresen und Atrophien betreffen besonders den Schultergürtel sowie Fuß- und Zehenextensoren, wohingegen die Beuger verschont sind.Nach klinischem Befund, elektromyographischen und -neurographischen Untersuchungen sowie den Ergebnissen der Muskel- und Nervenbiopsie (N. suralis) wird das Syndrom in die Gruppe des Dawidenkowschen Typs der scapulo-peronealen Amyotrophie mit autosomal dominantem Erbgang eingeordnet.Auf differentialdiagnostische Fragen, die sich aus der Kombination des myopathischen Prozesses mit polyneuropathisch begrenzten Sensibilitätsstörungen und Reflexabschwächung ergeben, wird anhand ähnlicher Beobachtungen in der Literatur eingegangen.

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The differential diagnosis of scapuloperoneal amyotrophy

Summary This report deals with a scapuloperoneal syndrome which developed simultanously with pain and distal paresthesias. In addition there was a slight sensory disturbance of glove and stocking type distribution. Motor conduction velocity was within normal limits and all distal latencies of response were normal; only the sensory conduction velocity of the left median nerve was found to be decreased (42.1 m/s). Electromyographic investigations revealed only signs of myopathy.Histological findings (m. deltoideus, m. tibialis anterior) favoured a primary myopathic process. Biopsy of the n. suralis revealed no certain pathological changes. The affection appears to have an autosomal dominant mode of inheritance.The sensory disturbance and decreased reflexes indicate an involvement of the nervous system, but the question of relationship to the scapuloperoneal muscular atrophy cannot yet be answered.

     

Enzymatic analysis of individual posterior root ganglion cells in olivopontocerebellar atrophy, amyotrophic lateral sclerosis and Duchenne muscular dystrophy

Four enzyme activities related to glucose metabolism, i.e. those of glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49), lactic dehydrogenase (LDH; EC 1.1.1.27), pyruvate dehydrogenase complex (PDC) and citrate synthase (CS; EC 4.1.3.7) were estimated in posterior root ganglion cells (PRGCs) of the spinal cord in patients suffering from olivopontocerebellar atrophy (OPCA), amyotrophic lateral sclerosis (ALS), and Duchenne muscular dystrophy (DMD) by means of the NAD, NADP and CoA cycling methods. In ALS and DMD, the enzyme activities examined were within normal ranges. In OPCA, PDC activity was significantly reduced and LDH activity tended to be lower than that in controls.     

Mitochondrienveränderungen im Skeletmuskel bei neuraler Muskelatrophie (Charcot-Marie-Tooth)

Zusammenfassung Es wird über zwei Schwestern im Alter von 38 und 44 Jahren berichtet, deren klinische Symptomatik sich dem Krankheitsbild der neuralen Muskelatrophie zuordnen läßt. Biopsien wurden aus funktionell intakten proximalen Muskelgruppen (M. deltoideus, M. rectus femoris) sowie dem N. suralis entnommen. Die histologisch-histochemische Untersuchung ergab kein neurogenes Schädigungsmuster, sondern Hinweise auf einen myopathischen Prozeß mit selektivem Befall der Typ 1-Fasern. Elektronenmikroskopisch fanden sich ausgeprägte Struktur- und Formanomalien der Mitochondrien mit parakristallinen Einschlußkörpern. Die Bedeutung der Befunde wird an Hand der einschlägigen Literatur diskutiert.

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Mitochondrial changes of the skeletal muscle in the peroneal muscular atrophy (Charcot-Marie-Tooth Disease)Histological and electron microscopic studies

Summary This report deals with two sisters (38 and 44 years old) suffering from Charcot-Marie-Tooth disease. Muscle biopsies were taken from the deltoid and the rectus femoris. In one of the cases a sural nerve biopsy was also made. Light microscopy showed only slight myopathic changes. The histochemical reactions disclosed an increase in lipid deposition and in NADH-TR activity of type 1 fibres. Electron microscopy showed abnormal mitochondrial aggregates, which were surrounded inconstantly by glycogen deposits, especially in the subsarcolemmal space. Many of the atypical mitochondria showed paracristalline inclusions within the cristae. The significance of these findings is discussed and compared with similar reports in the literature.

     

Muscle glucose-6-phosphate dehydrogenase deficiency: Restoration of enzymatic activity in hybrid myotubes

A high level of glucose-6-phosphate dehydrogenase (G6PD) activity was observed in myoblasts and myotubes from normal human and mouse cell cultures. However, only a residual amount of activity was observed in myoblasts and myotubes obtained from G6PD-deficient patients (G6PD Mediterranean). Hybrids were formed by the fusion of normal (from human and mouse) and G6PD-deficient myoblasts (from the patients). These hybrids contained a high level of G6PD activity. Hoechst staining permitted to confirm that the enzymatic activity was not restrained to a domain near the competent nuclei. These results suggest that myoblast transplantation could be used to restore normal enzymatic activity in metabolic myopathies.