Regional body composition and functional impairment in patients with myotonic dystrophy.

INTRODUCTION: In this study we determined regional body composition in myotonic dystrophy (DM1) and able-bodied controls and evaluated the relationship between fat and lean tissue mass and functional impairment in DM1 patients. METHODS: Dual-energy X-ray absorptiometry (DEXA) was used to obtain regional measurements of fat-free mass index (FFMI) and fat mass index (FMI) in 48 DM1 and anthropometrically matched control pairs. RESULTS: DM1 patients had lower regional FFMI and higher FMI than controls (P < 0.01-0.001). In DM1 patients, total FMI increased significantly with increased muscular disability rating, decreased motor function measurement, and with both decreasing vital capacity and total lung capacity. Hypertriglyceridemia correlated with increasing FMI. CONCLUSIONS: Regional FFMI is decreased in DM1, whereas FMI is underestimated by body mass index and is negatively correlated with patients' functional capacity. DEXA may provide valuable supporting evidence in the management of DM1.

Subacute myopathy in a mature patient due to multiple acyl-coenzyme A dehydrogenase deficiency.

INTRODUCTION: Multiple acyl-coenzyme A dehydrogenase deficiency (MADD), also called glutaric aciduria type II, is an inherited metabolic disorder resulting from a deficiency in electron transfer flavoprotein (ETF) or of its ubiquinone oxidoreductase (ETF-QO). It usually occurs in the neonatal period or in early infancy and, very rarely, in adolescents and young adult patients. METHODS: We report the case of a 55-year-old woman who developed a painful subacute myopathy. RESULTS: Lipid accumulation was found at biopsy. MADD was confirmed by plasma acylcarnitine profile and by assessment of ETF-QO activity in muscle. CONCLUSIONS: This study demonstrates that metabolic myopathies usually found in infancy may be also diagnosed in older patients. MADD may be easily treated by riboflavin and coenzyme Q10 and therefore should be included in the differential diagnosis of adult-onset painful myopathy.

Supine changes in lung function correlate with chronic respiratory failure in myotonic dystrophy patients.

Quality of life and prognosis of patients with myotonic dystrophy type 1 (MD1) often depend on the degree of lung function impairment. This study was designed to assess the respective prevalence of ventilatory restriction, hypoxaemia and hypercapnia in MD1 patients and to determine whether postural changes in lung function could contribute to the early diagnosis of poor respiratory outcome. Fifty-eight patients (42.6±12.9 years) with MD1 were prospectively evaluated from April 2008 to June 2010 to determine their supine and upright lung function and arterial blood gases. The prevalence of ventilatory restriction was 36% and increased with the severity of muscular disability (from 7.7% to 70.6%). The prevalence of hypoxaemia and hypercapnia was 37.9% and 25.9%, respectively. Multiple regression analysis showed that the supine fall in FEV1 was the only variable associated with ventilatory restriction, hypoxaemia and hypercapnia. Our data indicate that supine evaluation of lung function could be helpful to predict poor respiratory outcome, which is closely correlated with hypoxaemia and/or hypercapnia.

[Increasing risk of tumors in myotonic dystrophy type 1]. / Augmentation du risque de tumeurs dans la dystrophie myotonique de type 1.

OBJECTIVE: Myotonic dystrophy type 1 (DM1) is characterized by an unstable expansion of a CTG repeat resulting in altered mRNA biogenesis. Benign or malignant tumours are increasingly reported. The aim of the study was to evaluate the risk of tumor in a cohort of patients DM1. METHOD: We retrospectively reviewed the medical records of every DM1 patient admitted in our neuromuscular center. Diagnoses of cancer and age at diagnosis were noted. The relative risk of a selected cancer was calculated using the data of the cancer registry obtained from the French "Institut de Veille Sanitaire". RESULTS: A total of 109 French DM1 patients, aged 44.1±13.0 years, were studied, and 14 malignant tumours were observed, with a significant relative risk (RR) of thymoma, of gynaecologic cancers, of lung cancers. CONCLUSION: While this cohort is small, our findings nevertheless suggest an increased risk of particular cancers in DM1. The toxic effects of mutant RNA may possibly affect oncogene expression or growth factor signalling pathways in cells. Clinical practice should include cancer screening and prevention of risk factors in DM1 patients.

Age, conduction defects and restrictive lung disease independently predict cardiac events and death in myotonic dystrophy.

OBJECTIVE: The aim of the study was to identify, in addition to conduction defects, possible predictors of cardiac events and death in patients with myotonic dystrophy (DM1). METHODS AND DESIGN: A retrospective observational cohort study was undertaken. Baseline clinical and non-invasive cardiac and respiratory investigations were obtained from 107 DM1 patients, who were regularly re-examined. Primary end-points were occurrence of cardiac events (pacemaker implantation or tachyarrhythmia) or death. Probability of an event was calculated using the Kaplan-Meier method, while contributing factors were assessed using univariate and multivariate (Cox model) analyses. RESULTS: Cardiac events occurred in 34 patients (29%). Age, muscular impairment, infantile onset, restrictive lung disease (RLD), ECG conduction defects, left ventricular ejection fraction (LVEF) below 50%, and arrhythmia detected during Holter monitoring were predictors of cardiac events. Multivariate analysis indicated that age, RLD, ECG conduction defects, Holter arrhythmia and LVEF remained independent predictors. Probability of cardiac events was 2.5% (5%CI: 0-7%) at 1 year and 6% (5%CI: 0-14%) at 3 years in patients younger than 42 years with normal ECG, Holter, LVEF and lung volumes. Advancing age, distal or proximal weakness and RLD characterized all non-survivors (n=14). CONCLUSION: Cardiac events or death are predicted not only by conduction defects or cardiomyopathy in DM1, but also by RLD, muscular disability and advancing age. Addition of these criteria should modulate time intervals for patient follow-up examinations. In young patients with normal baseline investigations, screening investigations every 2 or 3 years seem to be sufficient.

IgG deficiency and expansion of CTG repeats in myotonic dystrophy.

OBJECTIVES: Expansion of CTG repeats in myotonic dystrophy (DM1) alters the regulated expression of numerous genes. It is considered to explain the major clinical features of DM1. IgG deficiency is common in DM1 and is due to altered FcRn-related hypercatabolism. We hypothesized that the IgG catabolic rate is correlated with CTG repeat expansion. METHODS: Correlations between serum immunoglobulin levels, peripheral lymphocyte subset counts and CTG repeat numbers were performed in 52 DM1 patients. RESULTS: Serum IgG and IgG1 levels were below the normal limit respectively in 54% and 72% of patients. Increasing CTG repeat numbers were significantly correlated with decreasing serum IgG and IgG1 levels, and with decreasing CD3(+) T-cell and CD3(+)-CD8(+) cell counts. An abnormal immunoglobulin profile at protein electrophoresis was found in 4 patients. CONCLUSION: We conclude that the catabolic rate of IgG is linked to expanded CTG repeats, possibly involving an altered immune response.

Organ dysfunction and muscular disability in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and multiple organ impairment, especially the eyes, lung, and heart. We conducted the current study to analyze the prevalence and intercorrelation among these disorders and their respective relationships with muscular disability. We assessed medical history, anthropometric data, lung volumes, arterial and venous blood samples, surface 12-lead electrocardiogram, echocardiography, ophthalmologic examination, and muscular impairment rating scale (MIRS) in 106 patients (48 male and 58 female) with DM1, aged 43.7 ± 12.8 years. Obesity, hypertriglyceridemia, and diabetes were found in respectively 25.6%, 47.6%, and 17.1% of patients. Disabling cataract was found in 43.4%, and was independently predicted by age and MIRS. Restrictive lung disease was noted in 34%, and was predicted by MIRS, CTG repeat expansion, and body mass index. Conduction disorders were found in 30.2% of patients and were predicted by left ventricular ejection fraction, MIRS, and CTG repeat expansion.We found significant relationships between cataract, restrictive lung disease, and conduction disorders: patients with cataract and those with conduction disorders exhibited more severe restrictive lung disease than the other patients. Conversely, the relative risk of restrictive lung disease was 2.42 (1% confidence interval [CI], 1.06-5.51) in patients with cataract and 2.54 (1% CI, 1.26-5.07) in patients with conduction disorders. Multivariate analysis revealed that MIRS was the only independent predictor for conduction disorders and restrictive lung disease. MIRS ≥3 and MIRS ≥4 were the best simple cutoff values to predict, respectively, lung and cardiac involvements.To conclude, muscular disability, ophthalmologic, and cardiac and pulmonary involvement are strongly correlated. Particular attention should be given to these entities in patients with distal or proximal muscular weakness.

Iliopsoas hematoma in Gaucher's disease.

Gaucher's disease is an autosomal recessive inherited disease characterized by oraganomegaly, cytopenia and bone destruction. Clotting disorders and platelet dysfunctions are described. We report the case of a 22-year-old man who presented subacute groin pain due to spontaneous iliopsoas hematoma. Laboratory investigations found moderate thrombocytopenia, normal coagulation factor activities and unspecific platelet function test disturbances. His spleen was moderately enlarged and no significant bone lesions were found. Iliopsoas hematoma is a rare complication in Gaucher's disease and should be included in the differential diagnosis of pain localized to the groin-hip area, which could rather evoke hip osteonecrosis in this context.