[Clinical and imaging features and genetic analysis of a case with adult-onset Krabbe disease].

OBJECTIVE: To investigate clinical and imaging features of a patient with adult-onset Krabbe disease and to detect the underlying genetic mutations. METHODS: Clinical and cranial MRI features of the patient were analyzed. Pathogenesis, clinical manifestation, cranial MRI features and diagnostic criteria for the disease were discussed. RESULTS: The patient had presented asymmetric limb weakness and difficulty in walking. Electromyography suggested peripheral nerve demyelination. Cranial MRI showed increased signal intensity in white matter with involvement of the corticospinal tracts. Screening of GALC gene mutation has found the patient to be heterozygous for T1685C (Ile562Thr) and homozygous for A1921G (Thr641Ala), both of which were considered to be polymorphisms. In addition, he was heterozygous for G136T (Asp46Tyr), which had not been described previously. CONCLUSION: Clinical manifestations of adult-onset Krabbe disease may be atypical. Cranial MRI and galactocerebroside activity assay should be carried out for patients featuring chronic progressive corticospinal tract injury. An Asp46Tyr mutation probably underlies the disease in the current case.

[Detection for trinucleotide repeats in myotonic dystrophy type 1].

OBJECTIVE: To establish an efficient method which can be easily used for detecting CTG trinucleotide repeats in myotonic dystrophy type 1 (DM1). METHODS: Tri-primer polymerase chain reaction (TP-PCR) combined with electropherogram was used to detect CTG repeats in the 3'-untranslated region of DMPK gene. Twenty non-related DM1 patients and 24 healthy controls were selected. RESULTS: All patients were found to have carried pathologic alleles containing more than 100 CTG repeats, while the healthy controls have carried 5-37 CTG repeats. CONCLUSION: TP-PCR combined with electropherograms may provide a highly sensitive, specific and accurate method which is less time-consuming and easier to perform for the detection of pathologic alleles in DM1 patients.

Tacrolimus treatment for relapsing-remitting chronic inflammatory demyelinating polyradiculoneuropathy: Two case reports.

BACKGROUND: This study describes the efficacy of a tacrolimus treatment regimen used to treat two patients with relapsing-remitting chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). CASE SUMMARY: Two patients (17-year-old female and 27-year-old male) were enrolled in the current study and were followed up for 12 mo. The first patient was administered tacrolimus (2 mg/d) for 12 mo and prednisolone (40 mg/d) for six months. The second patient was administered tacrolimus (3 mg/d) for six months. Both patients were followed up for 12 mo and the degree of recurrent weakness or normalized motor function was monitored. In addition, nerve conduction studies and tacrolimus levels were recorded. Following tacrolimus treatment, both patients showed marked improvement in clinical outcomes. In the first patient, prednisolone treatment was successfully withdrawn after six months. Sensory as well as motor nerve conduction velocities showed evident recovery following treatment. However, conduction velocities did not completely return to normal, suggesting that electrophysiological recovery can be slower than clinical recovery. CONCLUSION: Neither patient exhibited any adverse effects due to the tacrolimus therapy. Therefore, tacrolimus can be effective for the treatment of patients with steroid-resistant CIDP.

Pathological Observation of Blood Stasis Syndrome in Non-diabetic Peripheral Neuropathies: A Retrospective Analysis Based on Nerve Biopsy.

OBJECTIVE: To investigate the pathological features of blood stasis syndrome (BSS) in non-diabetic peripheral neuropathy. METHODS: Clinical data of 31 patients with non-diabetic peripheral neuropathy who had undergone nerve biopsy during December 2004 and December 2010 in Xuanwu Hospital Capital Medical University were retrospectively analyzed. According to Chinese medicine (CM) syndrome differentiation and signs, 26 patients were blood stasis type and 5 patients were non-blood stasis type. Clinical and pathological data were compared in detail. RESULTS: Clinically, although both groups shared similar symptoms of limb numbness, weakness and sensory disturbances, the prevalence of neuralgia was much grievous in BSS group (73.1%, 26/31) compared with the non-BSS group (0%, 0/5). As for signs, dermal nutrients disturbance (84.6%, 22/26), dark or purple tongue (100.0%, 26/26), and sublingual varices (80.7%, 21/26) were more common in the BSS group than the non-BSS group (0%, 60%, 20%, respectively). The prevalence of qi deficiency cases (19/26) in the BSS group was significantly higher compared with the non-BSS group (1/5). The unique histological manifestations of BSS were axonal degeneration (16/26 vs 2/5 in non-BSS group), which was the hallmark of ischemia. Cases with BSS had prominent microangiopathy (61.5%, 16/26), manifested as epineurium vasculitis (inflammatory cell infiltrated to the vessel wall, obliteration and recanalization, vascular proliferation, extravascular hemosiderin deposition), angiotelectasis, proliferation and hyaline degeneration of endoneurium capillary. In the BSS group, impaired blood-nerve barrier was indicated by sub-perineurial edema (46.2%, 11/26) and endoneurial edema (15.4%, 4/26). The Renaut body (15.4%, 4/26) and amyloid deposition (3.8%, 1/26) found in the BSS group were absent in the non-BSS group. CONCLUSIONS: BBS was common in non-diabetic peripheral neuropathies. The nerves exhibited ischemic alteration of primary axon degeneration and secondary demyelination. The interstitial tissue revealed microcirculation impairment, blood-nerve barrier disturbance, amyloid deposition and proliferation changes. The high prevalence of qi deficiency also highlights the therapy of promotion of blood circulation and removal of blood stasis.

Identification of the CFTR c.1666A>G Mutation in Hereditary Inclusion Body Myopathy Using Next-Generation Sequencing Analysis.

Hereditary Inclusion Body Myopathy (HIBM) is a rare autosomal dominant or recessive adult onset muscle disease which affects one to three individuals per million worldwide. This disease is autosomal dominant or recessive [corrected] and occurs in adulthood. Our previous study reported a new subtype of HIBM linked to the susceptibility locus at 7q22.1-31.1. The present study is aimed to identify the candidate gene responsible for the phenotype in HIBM pedigree. After multipoint linkage analysis, we performed targeted capture sequencing on 16 members and whole-exome sequencing (WES) on 5 members. Bioinformatics filtering was performed to prioritize the candidate pathogenic gene variants, which were further genotyped by Sanger sequencing. Our results showed that the highest peak of LOD score (4.70) was on chromosome 7q22.1-31.1.We identified 2 and 22 candidates using targeted capture sequencing and WES respectively, only one of which as CFTRc.1666A>G mutation was well cosegregated with the HIBM phenotype. Using transcriptome analysis, we did not detect the differences of CFTR's mRNA expression in the proband compared with healthy members. Due to low incidence of HIBM and there is no other pedigree to assess, mutation was detected in three patients with duchenne muscular dystrophyn (DMD) and five patients with limb-girdle muscular dystrophy (LGMD). And we found that the frequency of mutation detected in DMD and LGMD patients was higher than that of being expected in normal population. We suggested that the CFTRc.1666A>G may be a candidate marker which has strong genetic linkage with the causative gene in the HIBM family.

Corrigendum: Identification of the CFTR c.1666A>G Mutation in Hereditary Inclusion Body Myopathy Using Next-Generation Sequencing Analysis.

[This corrects the article DOI: 10.3389/fnins.2018.00329.].

[A study of vascular factor in the pathogenesis of polymyositis].

OBJECTIVE: To study ICAM-1, IL-1alpha expression in capillaries and to explore whether capillaries play a role in the pathogenesis of polymyositis. METHODS: Ten cases of patients with polymyositis and 6 patients with other myopathies were collected. CD34, ICAM-1 and IL-1alpha were selected for a quantitative measurement using an image analysis system, and results were presented as the percent of positive staining in the tissue area. RESULTS: We found that the percent of capillaries in tissues from polymyositis was significantly less than that from controls (P = 0.009). ICAM-1 and IL-1alpha expression in endothelial cells of capillaries were stronger in polymyositis patients. CONCLUSION: Our findings indicated that changes of capillaries might participate in the pathogenesis of polymyositis.

An unusual case with myotonia.

We report an unusual case involving a patient with myotonia. A 57-year-old man had multisystemic symptoms including skeletal muscle weakness, atrophy and percussion myotonia, cataract, heart involved, gastrointestinal tract symptoms, and urinary incontinence. The electromyography revealed myotonic discharges. Muscle biopsy showed myopathic features and a striking number of ring fibers. It was genetically proven that the case was not myotonic dystrophy type 1 (DM1) or 2 (DM2). The case might be DM3 or an unusual case of unclassified myopathy with multisystemic damage.

Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene.

Giant axonal neuropathy is a rare autosomal recessive disorder, which typically involves both central and peripheral nervous system. Yet the phenotypic-genotypic correlation remains obscure. We report a novel compound heterozygous mutation with the c. 805C>T in exon 4(Arg545His missense mutation) and the c. 1634G>A in exon 11(Arg269Trp missense mutation) in an 11-year-old Chinese giant axonal neuropathy case. This patient had an atypical giant axonal neuropathy phenotype rather similar to Charcot-Marie-Tooth disease, without tightly curled hair and mental retardation. The patient had a slowly progressive sensory motor neuropathy since age 3 years, and she also had nystagmus, feet deformities, scoliosis, and cerebellar tonsillar protrusion. Electrophysiological studies indicated a predominantly axonal sensory-motor neuropathy. The diagnosis was confirmed by sural nerve biopsy and direct sequencing of all the 11 gigaxonin exons. The proband's parents are heterozygotes of the disease without symptoms. Our findings extend the number of gigaxonin mutations that cause giant axonal neuropathy.