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This study summaries the current management of scoliosis in patients with Duchenne Muscular Dystrophy. A literature review of Medline was performed and the collected articles critically appraised. This literature is discussed to give an overview of the current management of scoliosis within Duchenne Muscular Dystrophy. Importantly, improvements in respiratory care, the use of steroids and improving surgical techniques have allowed patients to maintain quality of life and improved life expectancy in this patient group., Competing Interests: The authors have no conflicts of interest to declare.

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype., (© 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.)

Background: Haploinsufficiency of PMP22 causes hereditary neuropathy with liability to pressure palsies. However, the biological functions of the PMP22 protein in humans have largely been unexplored owing to the absence of patients with PMP22-null mutations., Objective: To investigate the function of PMP22 in the peripheral nervous system by studying a boy without the PMP22 gene and mice without the Pmp22 gene., Design: The clinical and pathological features of a patient with a PMP22 homozygous deletion are compared with those of Pmp22-null mice., Setting: Clinical evaluation was performed at tertiary hospitals in the United Kingdom. Molecular diagnosis was performed at the West Midlands Regional Genetics Laboratory. Immunohistochemistry and electron microscopy analyses were conducted at Wayne State University, Detroit, Michigan. Analysis of the Pmp22 +/- and null mice was performed at Vanderbilt University, Nashville, Tennessee., Participant: A 7-year-old boy without the PMP22 gene., Results: Motor and sensory deficits in the proband were nonlength-dependent. Weakness was found in cranial muscles but not in the limbs. Large fiber sensory modalities were profoundly abnormal, which started prior to the maturation of myelin. This is in line with the temporal pattern of PMP22 expression predominantly in cranial motor neurons and dorsal root ganglia during embryonic development, becoming undetectable in adulthood. Moreover, there were conspicuous maturation defects of myelinating Schwann cells; these defects were more significant in motor nerve fibers than in sensory nerve fibers., Conclusions: Taken together, the data suggest that PMP22 is important for the normal function of neurons that express PMP22 during early development, such as cranial motor neurons and spinal sensory neurons. Moreover, PMP22 deficiency differentially affects myelination between motor and sensory nerves, which may have contributed to the unique clinical phenotype in the patient with an absence of PMP22.

Purpose: To evaluate the efficacy of using combined glucose and fructose (GF) ingestion as a means to stimulate short-term (4 h) postexercise muscle glycogen synthesis compared to glucose only (G)., Methods: On two separate occasions, six endurance-trained men performed an exhaustive glycogen-depleting exercise bout followed by a 4-h recovery period. Muscle biopsy samples were obtained from the vastus lateralis muscle at 0, 1, and 4 h after exercise. Subjects ingested carbohydrate solutions containing G (90 g x h(-1)) or GF (G = 60 g x h(-1); F = 30 g x h(-1)) commencing immediately after exercise and every 30 min thereafter., Results: Immediate postexercise muscle glycogen concentrations were similar in both trials (G = 128 +/- 25 mmol x kg(-1) dry muscle (dm) vs GF = 112 +/- 16 mmol x kg(-1) dm; P > 0.05). Total glycogen storage during the 4-h recovery period was 176 +/- 33 and 155 +/- 31 mmol x kg(-1) dm for G and GF, respectively (G vs GF, P > 0.05). Hence, mean muscle glycogen synthesis rates during the 4-h recovery period did not differ between the two conditions (G = 44 +/- 8 mmol x kg(-1) dm x h(-1) vs GF = 39 +/- 8 mmol x kg(-1) dm x h(-1), P > 0.05). Plasma glucose and serum insulin responses during the recovery period were similar in both conditions, although plasma lactate concentrations were significantly elevated during GF compared to G (by approximately 0.8 mmol x L(-1), P < 0.05)., Conclusions: Glucose and glucose/fructose (2:1 ratio) solutions, ingested at a rate of 90 g x h(-1), are equally effective at restoring muscle glycogen in exercised muscles during the recovery from exhaustive exercise.

Although it is known that exercise exerts a positive regulatory effect on collagen synthesis, the effects of endurance training on muscle endomysial connective tissue in man are not so well documented. To investigate this, a single muscle biopsy was collected from two groups of volunteers - endurance-trained sports participants and age-matched healthy untrained individuals. Endomysial staining intensity of types I, III and IV collagen was quantified by immunohistochemical staining and image analysis methods. Gelatinase activity in the endomysium was also quantified histochemically. Mean cycling VO2peak values of 53+/-6 (SD) and 32+/-8 mL/kg/min (P<0.01) were recorded for the trained and untrained groups, respectively. The staining intensity of types I, III and IV collagen and gelatinase activity in the trained group were not significantly different from the untrained group. However, when the data for all 11 volunteers were pooled, significant negative correlations were found for type III collagen staining intensity and capillary/fiber ratio; and for the relationship between type IV collagen staining intensity and VO2peak. These results suggest a negative association between aerobic capacity and the intensity of staining for types III and IV collagen in muscle endomysium.

The purpose of this study was to investigate the effects of high-force eccentric muscle contractions on collagen remodeling and on circulating levels of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in humans. Nine volunteers [5 men and 4 women, mean age 23 (SD 4) yr] each performed a bout of 100 maximum voluntary eccentric contractions of the knee extensors. Muscle biopsies were taken before exercise and on days 4 and 22 afterward. Image analysis of stained tissue sections was used to quantify endomysial collagen staining intensity. Maximum voluntary contractile isometric force was recorded preexercise and on days 1, 2, 3, 4, 8, 11, and 14 postexercise. Venipuncture blood samples were also drawn on these days for measurement of serum creatine kinase activity and concentrations of MMP-9, TIMP-1, TIMP-2, and the MMP-2/TIMP-2 complex. Maximum voluntary contractile force declined by 39 +/- 23% (mean +/- SD) on day 2 postexercise and recovered thereafter. Serum creatine kinase activity peaked on day 4 postexercise (P < 0.01). Collagen type IV staining intensity increased significantly on day 22 postexercise to 126 +/- 29% (mean +/- SD) of preexercise values (P < 0.05). Serum MMP-9 levels increased on day 8 postexercise (P < 0.01), and serum TIMP-1 was also significantly elevated on days 1, 2, 3, 4, and 14 postexercise (P < 0.05). These results suggest that a single bout of eccentric muscle contractions results in remodeling of endomysial type IV collagen, possibly via the MMP pathway.

We report a 4-year-old boy with multiple sulphatase deficiency (MSD). His early health was good. By the end of his first year there were concerns about developmental delay but by 26 months he showed clear evidence of regression in that he was barely able to sit unsupported and had lost all fine motor and communication skills. At that time he also had widespread mild ichthyosis that cleared completely with the use of emollients. The neurological deterioration suggested a diagnosis of metachromatic leucodystrophy, and a reduction in the leucocyte arylsulphatase A activity was detected. The ichthyosis suggested steroid sulphatase deficiency, and a reduction in the leucocyte steroid sulphatase activity was detected. The enzyme deficiency was much less marked for steroid sulphatase than for arylsulphatase A in this boy. This diversity in enzyme activities is typical of MSD and correlates with the mild ichthyosis in this child. This case shows that even mild ichthyosis should prompt measurement of steroid sulphatase activity in a child of either sex with unexplained neurological deterioration.

Central core disease (CCD) is a congenital myopathy due to dominant mutations in the skeletal muscle ryanodine receptor gene (RYR1). The authors report three patients from two consanguineous families with symptoms of a congenital myopathy, cores on muscle biopsy, and confirmed linkage to the RYR1 locus. Molecular genetic studies in one family identified a V4849I homozygous missense mutation in the RYR1 gene. This report suggests a congenital myopathy associated with recessive RYR1 mutations.

A 6 year old boy who presented with steroid unresponsive nephrotic syndrome is reported. He was found to have focal segmental glomerulosclerosis and associated hypoparathyroidism and sensorineural deafness. The child progressed to end stage renal failure and was successfully managed by dialysis and cadaveric renal transplantation. He later developed progressive neurological deterioration and mitochondrial myopathy and neuropathy was diagnosed.

Two unrelated patients of Pakistani origin presented with primary hyperoxaluria type 1 (PH1) at 4 months and 3 years of age, respectively. While the younger patient failed to thrive and suffered from early renal failure, the older one showed a relatively benign history with urolithiasis as the main feature of the disease. In both patients the diagnosis was confirmed by assessment of alanine:glyoxylate aminotransferase catalytic and immunoreactivity in liver biopsy specimens. The underlying genetic defect was found to be a combined deletion and insertion in exon 8 which alters the reading frame of the protein. The nucleotide change introduces a Stu1 restriction site which facilitated typing of additional family members. Both patients and a further affected brother were homozygous for this mutation, while their parents were heterozygous for it. This mutation is the first deletion/insertion identified in PH1. Although rare in our PH1 patient cohort (2.5% of alleles), the finding of 2 homozygous apparently unrelated individuals of the same ethnic origin suggests that it may prove worthwhile to screen other Asian patients for this mutation. These PH1 cases present further evidence that factors other than genotype contribute significantly to the clinical presentation and severity of PH1.

A 32 week, small for dates baby with aplasia cutis congenita had an unbalanced translocation, being monosomic for distal 12q and trisomic for distal 1q. As far as is known, the association between extensive skin defects and a chromosomal abnormality has not been reported before. Keratin genes have been located in a different area of 12q, but this case may indicate other candidate areas to explore. Karyotyping should be undertaken in all babies with aplasia cutis.

This study monitored plasma and skeletal muscle markers of free-radical-mediated damage following maximum eccentric and concentric exercise, to examine the potential role of free radicals in exercise-induced muscle damage. Fourteen male volunteers performed either (1) a bout of 70 maximum eccentric and a bout of 70 maximum concentric muscle actions of the forearm flexors (the bouts being separated by 4 weeks; n = 8) or (2) a bout of 80 maximum eccentric and a bout of 80 maximum concentric muscle actions of the knee extensors (the bouts being separated by 1 week; n = 6). Plasma markers of lipid peroxidation, thiobarbituric acid-reactive substances (TBARS) and diene-conjugated compounds (DCC) were monitored in the arm protocol and skeletal muscle markers of oxidative lipid and protein damage, malondialdehyde (MDA) and protein carbonyl derivatives (PCD) respectively, were monitored in the leg protocol. In both protocols, the contralateral limb was used for the second bout and the order of the bouts was randomised between limbs. Repeated measures ANOVA indicated significant changes from baseline following eccentric arm work on the measures of serum creatine kinase activity (P < 0.05), maximum voluntary torque production (P < 0.01) and relaxed arm angle (P < 0.01). Subjective muscle soreness peaked 2 days after eccentric arm work (P < 0.05, Wilcoxon test). However, there were no changes in the plasma levels of TBARS or DCC following the eccentric or concentric arm exercise. Immediately after concentric leg exercise, skeletal muscle PCD concentrations was significantly higher than that observed immediately after eccentric work (P < 0.05)(ABSTRACT TRUNCATED AT 250 WORDS)

Our understanding of neuromuscular disorders has advanced considerably in recent years with developments in molecular genetic techniques. In some conditions we now know the basic pathological defect and, in many, prenatal diagnosis is now available. This review considers the common clinical problems that confront clinicians.

Over a three year period 444 requests for the neonatal transfer of babies with acute medical problems were received at this regional neonatal medical unit. Despite an increase in available resources in the North Western Health Region the provision of intensive care remained inadequate with 38% of requests declined, and babies had to be referred elsewhere including to neighbouring health regions. The survival of those babies who had to remain at the hospital of birth (49%) was significantly lower than for those transferred to the regional centre (71%). Those babies declined admission had significantly lower gestational ages and birth weights than those accepted. For those babies with respiratory failure and birth weights of less than 1500 g within these two groups, however, there were no significant differences in birth weight, gestational age, or gender yet survival was significantly better for those transferred. Babies from multiple pregnancies caused particular problems if neonatal transfer was required.

The results of treatment are reviewed in 18 cases of childhood nasopharyngeal carcinoma. Since 1976 adjuvant chemotherapy with cyclophosphamide, methotrexate, and adriamycin has been used in Manchester and Leeds. The outcome is compared in 9 patients treated with radiotherapy alone and 9 patients treated later with both radiotherapy and adjuvant chemotherapy. Relapse-free survival rates were 0% for those treated with radiotherapy alone and 78% at 13-80 months after diagnosis for those treated with both radiotherapy and chemotherapy. It is concluded that adjuvant chemotherapy improves relapse-free survival in childhood nasopharyngeal carcinoma.