Gauthier Remiche

Screening for later-onset Pompe's disease in patients with paucisymptomatic hyperCKemia.

BACKGROUND Pompes disease is an inherited metabolic myopathy caused by acid α-glucosidase deficiency. Early diagnosis optimizes the treatment effectiveness. METHODS One-hundred-thirty-seven consecutive patients with unexplained hyperCKemia underwent the assessment of acid α-glucosidase activity on dried blood spot. Second tier confirmatory testing in positive patients included the assessment of α-glucosidase activity on lymphocytes or muscle tissue and molecular analysis. RESULTS Three patients were diagnosed with later-onset Pompes disease, revealing 2.2% prevalence in asymptomatic hyperCKemia. Moreover, three patients positive to the screening revealed abnormal biochemical second tier testing, but were heterozygous for the common c.-32-13T>G mutation at molecular level. CONCLUSIONS The selective screening for later-onset Pompes disease in asymptomatic hyperCKemia allowed the identification of affected patients in a pre-clinical stage. Additionally, the identification of carriers with biochemical alterations related to Pompes disease extends the spectrum of its manifestations to heterozygous subjects.

Incontinence in late-onset Pompe disease: an underdiagnosed treatable condition.

From our previously described LOPD cohort [20] , we studied only patients being clinically revisited (n = 20). Inclusion criteria for LOPD diagnosis were positivity for at least 2 of the following criteria: low GAA enzyme assay ( ! 30%) [8] , vacuolar myopathy and/or increased acid-phosphatase and/or periodic acid-Schiff stain and double GAA gene mutation. We systematically asked the patients if they had urinary or fecal incontinence, diarrhea or constipation. Main causes of incontinence such as central nervous system disease, peripheral nerve disease, dysautonomia or pelvic surgery were systematically and reasonably excluded by standardized detailed anamnesis and clinical examination in each patient. Women were asked to disclose their maternity status, and in men prostatism was assessed. The main Dear Sir, Late-onset Pompe disease (LOPD) is an autosomal recessive multisystemic lysosomal storage disease caused by acid alpha-glucosidase (GAA) deficiency [1–5] . Incidence of Pompe disease varies between 1: 40,000 and 1: 156,000 [6–8] . Except in myotonic dystrophy type 1 (DM1) [9–12] , incontinence is rarely reported in myopathies [13–15] . Nevertheless, it is a disabling condition in social as well as in professional life [16] . LOPD patients generally have nonhomogeneous muscle involvement (e.g. predominance of atrophy on the posterior compartment of the femoral muscles) [17] . To the best of our knowledge, incontinence has been reported in only 4 LOPD patients (2 urinary and 2 fecal) [18, 19] . Bernstein et al. [19] reported the case of an LOPD incontinent patient with subjective improvement after 3 months of enzyme replacement therapy (ERT). Pathophysiologic hypotheses for incontinence in myopathies include striated and smooth pelvic floor muscle as well as lower motor neuron or autonomic involvement [9–11, 14] . We aimed to assess the prevalence of fecal and urinary incontinence in LOPD and to determine if incontinent patients presented a more severe phenotype. We foReceived: January 2, 2012 Accepted: April 2, 2012 Published online: June 29, 2012

Impact of hyponatremia on nerve conduction and muscle strength

Hyponatremia is associated with unstable gait and propensity to falls. The potential contribution of peripheral nervous system dysfunction induced by hyponatremia has not yet been addressed by prospective studies.

Postural effects on lung and chest wall volumes in late onset type II glycogenosis patients.

Respiratory failure associated with diaphragmatic weakness is the first cause of death in late-onset type II glycogenosis (LO-GSDII). We aim to identify predictive factors of diaphragmatic weakness and investigate the pathophysiology of respiratory muscles impairment. Pulmonary function and chest wall volumes were measured in ten patients and eight controls (supine and seated). According to the change in forced vital capacity in supine (ΔFVC) we considered patients with (DW, ΔFVC>25%) and without (noDW, ΔFVC<25%) diaphragmatic weakness. Postural change made the supine abdominal contribution to tidal volume (%VAB) of DW to fall and the ribcage to increase and good correlation was found between %VAB and ΔFVC (R=0.776). Patients showed reduced chest wall and abdominal inspiratory capacity (ICCW and ICAB) (p<0.001) and low abdominal expiratory reserve volume (p<0.01). Passing to supine DW did not increase ICCW and ICAB. ΔFVC occurs in LO-GSDII due to weakened diaphragm and abdominal muscles while intercostals are preserved. %VAB represents a new reliable index to detect diaphragmatic weakness.

Spontaneous hydromyelic cavity in two unrelated patients with late-onset pompe disease: is this a fortuitous association?

Patient 1 A 56-year-old male patient was investigated for progressive limb weakness over the previous 3 years. Past medical and family history was unremarkable. Neurologic examination revealed a proximal quite symmetric weakness [Medical Research Council (MRC) score 3–4/5], without sensory disturbances or pyramidal signs. Because no etiologies were found to explain Dear Sir, Late-onset Pompe disease (LOPD) is an autosomal recessive lysosomal storage disease due to glucosidase alpha acid (GAA) deficiency leading to intracytoplasmic glycogen accumulation [1] . Prevalence of LOPD varies in populations at between 1: 40,000 and 1: 146,000 [2] . Hydromyelia is a dilatation of the spinal central canal which communicates with the intracranial cerebrospinal fluid compartment [3, 4] . It can lead to neurologic deficits including in some cases muscle weakness and atrophy [3, 5] . Hydromyelia is considered a rare condition [6] , but its exact incidence seems unknown. Syringomyelia arises primarily outside the central canal and secondary to Chi ari malformation, tumor, traumatism or bleeding [4, 5] . Its incidence is estimated at around 8.4 new cases/year/100,000 people [7] . In some cases, hydromyelia is considered a ‘pre-syringomyelic’ stage or a predisposition to syringomyelia [8, 9] . We report for the first time, 2 cases of association between hydromyelic cavity Received: January 21, 2013 Accepted: March 20, 2013 Published online: July 9, 2013