Long-term observation of patients with advanced late-onset Pompe disease undergoing enzyme replacement therapy: A 15-year observation in a single center.

BACKGROUND: There have been few descriptions in the literature on long-term enzyme replacement therapy (ERT) in patients with advanced late-onset Pompe disease (LOPD). OBJECTIVES: This study aimed to assess the efficacy and limitations of ERT in advanced LOPD patients. METHODS: We retrospectively reviewed the clinical courses of patients with advanced LOPD (two juvenile-onset and five adult-onset patients) who were treated with recombinant human alglucosidase alfa to examine improvements achieved with and limitations of ERT until their death or when switching to avalglucosidase alfa occurred. RESULTS: All patients were non-ambulant and ventilator dependent. The duration of follow-up ranged from 3.7 to 15.0 years (median 9.0 years). All patients reported improvements in their lives during the first two or three years of ERT. Vital capacity was clearly improved in patients with relatively spared respiratory function, although it deteriorated after respiratory complications such as pneumothorax. Pinch and grip power tended to be preserved during the treatment period. Muscle CT revealed progression of atrophy and fatty replacement predominantly in the proximal limb muscles without improvement after ERT. Four patients died due to aspergillosis, respiratory failure, ileus, and sudden death of unknown cause. CONCLUSIONS: Our findings demonstrate that patients undergoing ERT show certain improvements, even in the advanced stage of Pompe disease. Respiratory complications are lethal even during ERT, and early diagnosis and induction of therapy are critical. Muscle wasting progressed more severely in the proximal limbs, even after ERT.

Identification of a novel mutation and genotype-phenotype relationship in MEGF10 myopathy.

Mutations in MEGF10 are associated with early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). Recently, a mild variant phenotype of EMARDD has been reported in patients with multiple minicores in the myofibers. However, some reported patients had no clear cores. We present a patient who had progressive weakness since his 30 s and then developed severe respiratory failure at the age of 66 years and found that he had a novel mutation, p.G739R, in MEGF10. He had no clear core in the biopsied muscle. We summarize the clinical and genetic characteristics of the current and reported patients with MEGF10 and statistically evaluate the genotype-phenotype correlation. Results show that patients with missense mutations in at least one allele had significantly later onset than those with biallelic truncation mutations.

Neurogenic calf amyotrophy with CK elevation by entrapment radiculopathy; clinical, radiological, and pathological analyses of 18 cases.

OBJECTIVE: To characterize the clinical, radiological, and pathological manifestations of 18 cases showing neurogenic calf amyotrophy with creatine kinase (CK) elevation by entrapment radiculopathy (NCACKEER). METHODS: We retrospectively reviewed and evaluated the medical records of patients who complained of weakness or atrophy of the calf muscles in our department between 2004 and 2019. We identified 18 cases fulfilling the proposed criteria of NCACKEER. We extracted neurological, laboratory, neurophysiological, and neuroradiological data from all cases. Moreover, we evaluated biopsy specimens from the gastrocnemius in four cases. RESULTS: Eighteen NCACKEER cases exhibited the characteristic findings that can discriminate previously known myopathies or polyneuropathies affecting distal legs. We noticed male predominance (72%) with an average age at diagnosis of 65.6 years. Muscle weakness or atrophy was localized in the distal legs, with Achilles tendon reflexes absent in all cases. We observed elevated serum CK levels with a range from 237 to 2294 IU/L. All electromyography (EMG) studies showed neurogenic changes in the affected muscles. Lumbar spinal MRI exhibited either spinal canal stenosis at various vertebral levels or intervertebral foraminal stenosis at L4/5 and L5/S1 in all cases with significant straightening spinal and sacral alignments. All muscle biopsy specimens showed findings of neurogenic muscular degeneration with no inflammatory infiltrations. Cases with higher CK elevation had more necrotic muscle fibers. CONCLUSION: We established the clinical characteristics of NCACKEER. Evaluations of serum CK level and skeletal muscle CT imaging are useful for screening, and lumbar spinal MRI, EMG and/or muscle biopsy are necessary for diagnostic confirmation.

Muscle imaging in muscle dystrophies produced by mutations in the EMD and LMNA genes.

Identifying the mutated gene that produces a particular muscle dystrophy is difficult because different genotypes may share a phenotype and vice versa. Muscle MRI is a useful tool to recognize patterns of muscle involvement in patients with muscle dystrophies and to guide the diagnosis process. The radiologic pattern of muscle involvement in patients with mutations in the EMD and LMNA genes has not been completely established. Our objective is to describe the pattern of muscle fatty infiltration in patients with mutations in the EMD and in the LMNA genes and to search for differences between the two genotypes that could be helpful to guide the genetic tests. We conducted a national multicenter study in 42 patients, 10 with mutations in the EMD gene and 32 with mutations in the LMNA gene. MRI or CT was used to study the muscles from trunk to legs. Patients had a similar pattern of fatty infiltration regardless of whether they had the mutation in the EMD or LMNA gene. The main muscles involved were the paravertebral, glutei, quadriceps, biceps, semitendinosus, semimembranosus, adductor major, soleus, and gastrocnemius. Involvement of peroneus muscle, which was more frequently affected in patients with mutations in the EMD gene, was useful to differentiate between the two genotypes. Muscle MRI/CT identifies a similar pattern of muscle fatty infiltration in patients with mutations in the EMD or the LMNA genes. The involvement of peroneus muscles could be useful to conduct genetic analysis in patients with an EDMD phenotype.