Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

Creatine kinase (CK) has been associated with neuropathy, but the mechanisms are uncertain. We hypothesized that peripheral nerve function is impaired in subjects with persistent CK elevation (hyperCKemia) compared to age- and sex matched controls in a general population. The participants were recruited from the population based Tromsø study in Norway. Neuropathy impairment score (NIS), nerve conduction studies (NCS) and electromyography (EMG) in subjects with persistent hyperCKemia (n = 113; 51 men, 62 women) and controls (n = 128; 61 men, 67 women) were performed. The hyperCKemia group had higher NIS score than the controls (p = 0.050). NCS of the tibial nerve showed decreased compound motor action potential amplitude (p < 0.001), decreased motor conduction velocity (p < 0.001) and increased F-wave latency (p = 0.044). Also, reduced sensory amplitudes of the median, ulnar, and sural nerves were found. EMG showed significantly increased average motor unit potential amplitude in all examined muscles. CK correlated positively with glycated hemoglobin and non-fasting glucose in the hyperCKemia group, although not when controlled for covariates. The length dependent polyneuropathy demonstrated in the hyperCKemia group is unexplained, but CK leakage and involvement of glucose metabolism are speculated on.

To investigate the incidence of hyperCKemia in patients with neuromyelitis optica spectrum disorders (NMOSD) and to document the clinical characteristics of these patients.
Records from 439 NMOSD patients were retrospectively reviewed. Records of patients with hyperCKemia were analyzed.
Nineteen patients with seropositive aquaporin (AQP)-4 antibodies had elevated CK levels in the acute phase of the disease. The magnetic resonance imaging (MRI) findings presented as myositis changes. All CK levels were reduced to the normal range after methylprednisolone treatment.
Transient hyperCKemia might be a feature of NMOSD patients in the acute phase, more attention is recommended.

The aim of this multicenter study was to screen for late-onset Pompe disease in high-risk children with limb-girdle muscle weakness and nonspecific hyperCKemia using the dried blood spot (DBS) test. Seventy-two children from four pediatric neurology departments in Turkey were enrolled in the study: 37 with limb-girdle muscle weakness and 35 with nonspecific hyperCKemia. Acid α-glucosidase (GAA) activity was measured on DBS by tandem mass spectrometry. Six patients tested positively for Pompe disease. In three patients, one with the limb-girdle muscle weakness and two with nonspecific hyperCKemia, this was confirmed by genetic analysis. The overall frequency of late-onset Pompe disease in the study population was 4.2%. The c.1784C>T mutation found in one patient is a new mutation whereas the c.1655T>C mutation detected in the other two patients is not novel. In conclusion, Pompe disease should be suspected in patients with limb-girdle muscle weakness and nonspecific hyperCKemia. The DBS test is a safe and reliable method of diagnosis but must be confirmed by genetic analysis. In patients with a positive DBS test and negative genetic analysis, tissue assay of GAA should be considered.