Characteristics of clinical manifestations and molecular genetics of late-onset cobalamin C deficiency / 中华神经科杂志

Objective To investigate the characteristics of clinical manifestations and genetics of late-onset cobalamin (cbl) C deficiency,also named as combined methylmalonic acidemia and homocystinemia, cblC type. Methods We reviewed 26 late-onset cblC deficiency patients diagnosed in Qilu Hospital, Shandong University from 2012 to 2017 and analysed the clinical, biochemistry, neuroimaging, follow-up and MMACHC gene data. Results Among the 26 patients, male:female ratio is 11:15, with the age of diagnosis from 4 to 39 years and sibling comorbidity in 4 families. The clinical manifestaions of nervous system included spastic paraplegia,mental and behavior disorder,intelectual decline,epilepsy,ataxia,dystonia and peripheral neuropathy. There were four cases with proteinuria at onset. At first visit, the levels of serum total homocystinuria of all patients were elevated, from 61.4 to 193.4μmol/Lwith methylmalonic acidemia. The neuroimaging data of the 26 cases showed 11 with cerebral atrophy, 10 with thoracic spinal cord atrophy, five with brain parenchymal lesions, three with longitudinal myelopathy which were reversible in follow-up, one with syringomyelia, one with multiple cerebral artery stenosis. In all the cases, cobalamins were supplied parenterally and folate, betaine, L-carnitine, vitamin B6 were supplied orally during acute metabolic crisis, and the symptoms of acute encephalopathy disappeared but symptoms of spastic paraplegia had little improvement. In chronic stage, frequency of intramuscular injection of hydroxocobalamine could be decreased while the index can still be improved. All the 26 cases had definite mutations in MMACHC gene, the most common mutations of which were found to be c.482G>A(15/52) and c. 609G>A(13/52). Conclusions Homocystine is the important biomarker for cblC deficiency. Once diagnosed, parenteral hydroxocobalamin and oral betaine should be supplied for a lifetime with good prognosis. The most common mutations of MMACHC gene in our cases are c. 482G>A and c. 609G>A missense mutations.

Analysis of clinical and electrophysiological features in patients with hereditary neuropathy with liability to pressure palsy diagnosed by gene analysis / 中华神经科杂志

Objective To study the clinical and electrophysiological features of the patients with hereditary neuropathy with liability to pressure palsy ( HNPP) diagnosed by gene analysis.Methods Seven patients from two HNPP families were assessed on medical history, physical examination, electrophysiology findings and gene analysis.Results A clinical manifestation of acute, painless, recurrent peripheral nerve palsies was typical for HNPP.Median, ulnar and peroneal nerves were usually affected.Electrophysiology study revealed that prolonged distal motor latency and slowing nerve conduction velocity were prominent.Gene studies exhibited a deletion of the peripheral myelination protein 22 gene in all the seven patients.Conclusions HNPP usually affects areas where nerves are subject to entrapment, and many episodes are preceded by minor compression on the affected nerve.As a reliable screening tool in detecting HNPP, the electrophysiological study shows that segmental demyelination is most commonly seen at common nerve entrapment sites.

Analysis of the clinical, electrophysiological and genetic features of a family affected with hereditary neuropathy with liability to pressure palsies / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To delineate the clinical, electrophysiological and genetics features of a family where 4 members were affected with hereditary neuropathy with liability to pressure palsies (HNPP).</p><p><b>METHODS</b>Clinical features of the 4 patients were summarized. Electrophysiological examination and genetic analysis were carried out.</p><p><b>RESULTS</b>All of the patients showed recurrent motor and sensory disturbances after minor traction or constriction. Electrophysiology study revealed that the prolonged latency and reduced conduction velocity of peripheral nerve were general and with multiple sites of affection. The nerve locations liable to entrapment showed conduction block. A deletion mutation of peripheral myelin protein 22 (PMP22) gene was identified by genetic analysis.</p><p><b>CONCLUSION</b>HNPP usually affects areas where nerves are liable to entrapment, and presents with motor and sensory disturbances of the innervated areas. Electrophysiological study reveals general nervous demyelination. Genetic analysis can clarify the diagnosis of HNPP.</p>

Clinical features of Kennedy desease(Report of 3 cases) / 临床神经病学杂志

Objective To explore the clinical features of Kennedy disease .Methods The clinical data of 3 patients with Kennedy disease was respectively analyzed .Results All three patients were middle-aged male and had a chronic onset .Patients were mainly presented with the muscle weakness and fasciculation in the proximal limb and bulbar , and the symptoms grow progressively .Two patients were hyperplasia of mammary glands , 3 patients had high levels of serum creatine kinase , and 2 patients'serum testosterone level was increased .EMG detected a widespread neuronal damage in all three cases , and the sensory conductions were abnormal in 2 patients.Repeat numbers of CAG in exon 1 of androgen receptor gene of 2 patients were tested, and they were 57, 47 respectively.Conclusions The clinical features of Kennedy disease are muscle weakness and androgen insensitivity syndrome in male patient and EMG presented with motor neuron damaged .Repeat number of CAG in exon 1 of androgen receptor gene is increased.

The value of MRI in diagnosis of cubital tunnel syndrome / 实用放射学杂志

Objective To study the value of magnetic resonance imaging (MRI)in diagnosis of cubital tunnel syndrome (CuTS). Methods We studied the findings of electrophysiological examination and MRI in 30 elbows of 23 patients with CuTS and 15 elbows of 1 5 controls.We observed the motor conduction velocity (MCV),cross sectional area (CSA)and relative signal intensity (RSI)of the ulnar nerve acrossing the elbow at the point of largest size proximal to the entrapment point (CSA1 ,RSI1 )and the entrapment point (CSA2 ,RSI2 ).Then we calculated the ratio of CSA (CSAR=CSA1/CSA2 ),and the ratio of RSI (RSIR=RSI1/RSI2 ).Results The value of CSA1 and RSI1 was significantly greater than CSA2 ,RSI2 in the patient group (P<0.05).The value of CSA1 ,RSI1 , CSAR and RSIR in patients were significantly larger than that in controls (P<0.05).MCV was negatively correlated with CSA1 and CSAR in the patient group (r=-0.62,r=-0.53).There were no correlation between MCV and RSI1 ,RSIR in the patient group. The area under ROC curve of CSAR was the largest 0.94 (95% CI,0.83-1).The optimum cutoff point of CSAR was 1.83.The CSAR had sensitivity of 93.3% and specificity of 80% in diagnosis of CuTS.Conclusion MRI combined with the electrophysiologi-cal examination shows a high accuracy of locating the entrapment point of ulnar never lesion at the elbow.The CSAR of the ulnar nerve is the best MRI parameters in diagnosis of CuTS.

Clinical and magnetic resonance imaging findings in a family with hereditary spastic paraplegia with mutation in NIPA1 / 中华神经科杂志

Objective To study features of the MRI and clinic in a family with pure hereditary spastic paraplegia (PHSPG) type 6.Methods Target loci (SPG3, 4, 6, 8 10 and 12) linkage analysis was performed in a SPG pedigree having 6 affected individuals using microsatellite markers and NIPA1 gene was screened for mutation by PCR-amplification and sequencing. MRI of brain and cervical and thoracic spinal cord were examined in these 6 patients and 6 normal controls matched for age and sex by two independent radiologists blinded to the clinical diagnosis. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at the levels of C2～3, C7, T1～4, T9 were measured and data was statistically analyzed using the student's t test. Results A missense mutation of 316g→c in NIPA1 was identified in the affected subjects, presumably resulting in substitution of glutamic acid for arginine in residue 106. Evaluation of the brain MRI images revealed non-specific brain abnormalities. All patients presented thinning of cervical and upper thoracic spine with atrophy in both gray and white matter and enlarged subarachnoid cavity. In severe atrophic segments, a distinct boundary between grey and white matter was observed and the lesions in grey matter presented literal high intensity spots or patches with clear boundary on transaxial T2-weighted images (T2WI) and high signal intensity longitudinal strip on the sagittal T2WI. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at C2～3, C7, T1～4 were significantly smaller in patients than in controls, while at the T9 level only transverse diameter showed significant difference (7.22±0.08 vs 8.17±0.41, t=2.870, P=0.046). Conclusions These findings indicate that the disease process in patients with SPG6 might be confined to the cervical and thoracic spinal cord, with atrophy in both white and grey matter having a distinct boundary.