Acute recurrent rhabdomyolysis in a Chinese boy associated with a novel compound heterozygous LPIN1 variant: a case report.

BACKGROUND: LPIN1-related acute recurrent rhabdomyolysis (RM), first reported in 2008, is an autosomal recessive inherited metabolic disease. In recent years, LPIN1 gene variants have been identified as one of the main causes of severe RM in children in Western countries. The disease is extremely rare in China, and we report a case of acute recurrent RM caused by a novel compound heterozygous LPIN1 variant. CASE PRESENTATION: A 15-year-old Chinese boy presented with myalgia after strenuous exercise, accompanied by transient increases in serum creatine kinase and myoglobin and persistent hyperuricaemia and hyperbilirubinaemia. Genetic analysis using high-throughput genomic sequencing and Sanger sequencing revealed that there was a compound heterozygous variant in the LPIN1 gene of the proband: the paternal c.2047A > G(p.I683V) was an unreported missense variant, and the maternal c.2107_2108 insAGG(p.Q703delin sQE) was an unreported in-frame variant. CONCLUSIONS: In children with RM, LPIN1 variants should always be considered in the differential diagnosis. The clinical features of our case are atypical, which highlights the importance of an accurate diagnosis by genetic testing. If detected early, the condition may be controlled, and the prognosis may be improved.

Septin 9 Methylation in Nasopharyngeal Swabs: A Potential Minimally Invasive Biomarker for the Early Detection of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia, and an unfavorable outcome is usually attributed to advanced stage NPC. Current methods for the early diagnosis of NPC have limitations in clinical practice. The aim of this study was to investigate the diagnostic ability of Septin 9 methylation for NPC. A quantitative methylation-sensitive PCR (qMS-PCR) assay was developed to measure the methylation status and levels of Septin 9 in nasopharyngeal tissues and paired swabs from patients with NPC, chronic nasopharyngitis, and healthy donors. Methylated Septin 9 was detected in 92% (23/25) of NPC tissues and 25% (4/16) of nasopharyngitis controls (p < 0.05). High-frequency hypermethylation with decreased mRNA expression of Septin 9 in NPC was also identified. Further, Septin 9 methylation was identified in 90.5% (19/21) of NPC biopsies and 71.4% (15/21) of paired swabs, indicating a good concordance between the two sample types. In addition, methylated Septin 9 was found in 16 (72.7%) nasal swabs from 22 NPC patients, 2 of 19 (10.5%) nasopharyngitis, but not in any of the healthy controls (p < 0.01). The methylation score in nasal swabs of the NPC group was also significantly higher than that of non-NPC controls (p < 0.001). Moreover, receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.882 of Septin 9 methylation tests to discriminate NPC from non-NPC subjects. Our study demonstrated that frequent methylation of Septin 9 was present in NPC. Its detection in nasopharyngeal swabs may provide a minimally invasive and informative method for identifying early NPC cases.

Giant liposarcoma of the esophagus: A case report.

Liposarcomas rarely develop in the aerodigestive tract. Here, we present a primary esophageal liposarcoma that was discovered between the T3 and T7 levels of the esophagus during right pleural exploration of a 51-year-old male patient. The patient had presented with non-specific symptoms, including progressive dysphagia over the previous 6 mo, without complaints of chest or epigastric pain, regurgitation, or weight loss. A radical three-hole esophagectomy was performed. The tumor was extremely large (14 cm × 7.0 cm × 6.5 cm), but completely encapsulated. Upon histological examination, the tumor was diagnosed as a giant, well-differentiated esophageal liposarcoma with a dedifferentiated component. Non-specific radiological and endoscopic results during the clinical work-up delayed diagnosis until post-operative histology was performed. In this report, the clinical, radiological and endoscopic diagnostic challenges specific to the case are discussed, as well as the surgical and pathological findings.

[Relationship of plasma concentration of 5-fluorouracil with toxicity and response in patients with nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Because there are several mechanisms of activity and toxicity and inter-individual variation in pharmaco- dynamics of 5-fluorouracil (5-FU),it is difficult to predict the sensitivity and toxicity of 5-FU in an individual patient. This study was designed to assess inter-patient variation of 5-FU steady-state plasma concentration and the relationship of plasma concentration of 5-FU with toxic side effects and therapeutic response. METHODS: Twenty patients with nasopharyngeal carcinoma were treated with 5-FU combined with cisplatin(DDP). Blood samples were collected after 24 hours of infusion of 5-FU. Plasma concentrations of 5-FU were measured using high performance liquid chromatography(HPLC) with column temperature at 25 Celsius degree, flow rate at 1.3 ml/min, wave length at 260 nm and 1 mmol/l phosphate buffer (pH 3.0) as mobile phase. RESULTS: The plasma concentrations of 5-FU were normally distributed in the patients. No adverse effects were noted in the patients with plasma concentration of 5-FU lower than 600 microg/L, and severe toxic side effects were observed in the patients with plasma concentration of 5-FU greater than 1000 microg/L. The differences between plasma concentrations of 5-FU and each grade side effects reached statistical significance (P< 0.05). CONCLUSION: The plasma concentration of 5-FU have highly inter-individual variation in the patients with nasopharyngeal carcinoma. Plasma concentrations of 5-FU were associated with the toxicity and treatment response.

Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle.

Carnitine palmitoyltransferase I (CPT I), which is expressed as two distinct isoforms in liver (alpha) and muscle (beta), catalyzes the rate-limiting step in the transport of fatty acid into the mitochondria. Malonyl-CoA, a potent inhibitor of CPT I, is considered a key regulator of fatty acid oxidation in both tissues. Still unanswered is how muscle beta-oxidation proceeds despite malonyl-CoA concentrations that exceed the IC(50) for CPT Ibeta. We evaluated malonyl-CoA-suppressible [(14)C]palmitate oxidation and CPT I activity in homogenates of red (RG) and white (WG) gastrocnemius, soleus (SOL), and extensor digitorum longus (EDL) muscles. Adding 10 microM malonyl-CoA inhibited palmitate oxidation by 29, 39, 60, and 89% in RG, SOL, EDL, and WG, respectively. Thus malonyl-CoA resistance, which correlated strongly (0.678) with absolute oxidation rates (RG > SOL > EDL > WG), was greater in red than in white muscles. Similarly, malonyl-CoA-resistant palmitate oxidation and CPT I activity were greater in mitochondria from RG compared with WG. Ribonuclease protection assays were performed to evaluate whether our data might be explained by differential expression of CPT I splice variants. We detected the presence of two CPT Ibeta splice variants that were more abundant in red compared with white muscle, but the relative expression of the two mRNA species was unrelated to malonyl-CoA resistance. These results provide evidence of a malonyl-CoA-insensitive CPT I activity in red muscle, suggesting fiber type-specific expression of distinct CPT I isoforms and/or posttranslational modulations that have yet to be elucidated.