| Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy in childhood. This incurable disease is characterized by muscle wasting and loss of walking ability leading to complete wheelchair dependence by 12 years of age. Prolongation of walking is one of the major aims of management. The aim of this study was to assess whether glucocorticoid corticosteroids stabilize or improve muscle strength and walking ability in boys with DMD.METHODSClinical TrialsThe Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society developed practice parameters as strategies for DMD patients management based on analysis of data collected from 1966 to 2004, and concluded the optimum dose (0.75mg/kg/day) of prednisone treatment. It demonstrated that corticosteroid treatment with prednisone (0.75 mg/kg/day) increased muscle strength performance, and pulmonary function and significantly slowed down the progress of muscle weakness. We designed this study according to the corticosteroid treatment standard given above. DMD patients whom were diagnosed by either deletion detection of dystrophy gene or muscle biopsy at the age of 5 to 10 were enrolled. The patients were divided into prednisone treatment group and control group with the random, double-blind, controlled principle and with informed consents from the participants. The prednisone group was given a prednisone dosage of 0.75mg/kg/day for a three-months period, and 0.3mg/day vit C was given to the control group as placebo. The examine data of every patient were recorded. In this study,31 eligible DMD patients were collected,17 patients in prednisone group and 14 patients in control group. Every subject should accept examine such as muscle strength scoring, respiratory function test,9 meter walking and 9 stairs climbing test. Additionally, the weight, blood pressure, ophthalmology and kinase spectrum were also checked.Laboratory testsWe detect the deletion extent of the DMD gene by using the multiple-PCR system developed by our lab. Then Multiplex Ligation-dependent Probe Amplification was used to detect the deletion extent of patients whose DMD gene has not been detected by multiplex PCR method.RESULTSClinical trials:We summarize the data from each examination of prednisone group and the control group. The mean value of strength score, FVC, and the time of walking nine metres were calculated. Statistics show that the mean strength score and the mean FVC as well as the mean time of nine meters walking in the prednisone group were significantly improved after prednisone treatment. As for the details, the four mean strength scores of prednisone group were 37.7,39.1,40.3 and 40.0 respectively, while the mean scores in control group were 38.2,37.0,36.2 and 36.6. The four mean FVCs in the prednisone group were 1.24L, 1.13L,1.21L and 1.16L, and the mean FVCs in control group were 1.24L,1.13L,1.21L and 1.16L. The four mean time of nine meters walking in the prednisone group were 8.50s,7.19s,7.64s,7.07s, and the mean time in control group were 7.7s,7.6s,8.1s,7.6s. We calculate the difference of every pairs of four strength score, FVC, FEV1 and the time of nine meters walking, and the independent samples t test was conducted respectively. All the data are consistent with the results in leteratures, there is significant difference (P<0.05) between two groups after taking medicine (prednisone or vitamin C). The mean gain of weight in control group is 0.305kg and 0.684kg in the prednisone group. The difference between these two groups were significant (P<0.05). Refering to the data of blood pressure and CK, there is no significant difference between the prednisone group and the control group.Molecular Experiments: Among the 31 patients who have participated in this trial, DMD gene deletion was detected with multiple-PCR in 28 patients, while deletion was detected in 29 patients by MLPA among them one patient was a complex deletion. Two DMD patients were identified as dystrophy protein deficiency in sarcolemma and no deletion could be detected by multiple-PCR system. Pseudoachondroplasia (PSACH) is a common skeletal dysplasia and an autosomal dominant disorder caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). the region of 19p 13.1 harbors the gene for cartilage oligomeric matrix protein. Often the presenting features of PSACH are waddling gait recognized at the onset of walking, Joint pain during childhood, particularly in the large joints of the lower extremities, scoliosis and lumbar lordosis appeared simultaneously. Osteoarthritis occurs in patients'adolescence which implicates both lower extremities and spine. Additionally, ligamentous laxity and joint hyperextensibility is common, the disease also leads to a moderately severe form of disproportionate short-limb short stature and osteoarthritis. Radiographic diagnosis of pseudoachondroplasia is ideally made based on delayed epiphyseal ossification and irregular epiphyses and metaphyses of the long bones, short metacarpals and phalanges that show epiphyses and irregular metaphyses, anterior beaking or tonguing of the vertebral bodies on lateral view.We collected a three-generation family whith five members affected and a two-generation family in which three members was affected, typical short-limb dwarfism, spinal lordosis and varus appear in all the affected members of both families. Blood samples were obtained from patients and members of both families with informed consent. exons 8-19 of the COMP gene were amplified by PCR and each fragment was sequenced directly. We have identified a novel mutation in exon 14 of COMP gene in the first family, c.1552G>T(p.D518Y). In the second family, a c.815C＞T substitution was identified in exon 8 of COMP gene in the proband and his affected father and brother. In addition, we also collected a sporadic PSACH case, and the mutation c.1411-1419del (p.D471-D473del) was detected in this male patient, this mutation has not been reported.Cartilage oligomeric matrix protein gene has the character of allelic heterogeneity, mutations of the gene also arise multiple epiphyseal dysplasia(MED), another related skeletal dysplasias characterized by early onset arthritis, short statureand multiple epiphyseal dysplasia, but PSACH have more severe short stature than MED, The main differential point is that MED have less spine involvement.Clinically, patients with pseudoachondroplasia were most often misdiagnosed as achondroplasia. There were short limbs, knee varus, lordosis, short limb dwarfism in both diseases. However, there was a typical large head with frontal bossing, midface hypoplasia, trident configuration of the hands. In contrast to PSACH, the lim shortness in achondroplasia was present before and after birth. This was very important in genetic counseling. Skeletal dysplasia is a category of genetic disorders with different pathogenesis. Similar clinical manifestations might caused by different genes. We will discuss this issue in the article. |
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