Advances in metabolome information retrieval: turning chemistry into biology. Part II: biological information recovery

This work reports the second part of a review intending to give the state of the art of major metabolic phenotyping strategies. It particularly deals with inherent advantages and limits regarding data analysis issues and biological information retrieval tools along with translational challenges. This Part starts with introducing the main data preprocessing strategies of the different metabolomics data. Then, it describes the main data analysis techniques including univariate and multivariate aspects. It also addresses the challenges related to metabolite annotation and characterization. Finally, functional analysis including pathway and network strategies are discussed. The last section of this review is devoted to practical considerations and current challenges and pathways to bring metabolomics into clinical environments.     

Pyridoxine-dependent epilepsy: report on three families with neuropathology

Metabolic Brain Disease - Pyridoxine-dependent epilepsy (PDE) is a pharmacoresistant epileptogenic encephalopathy controlled by pyridoxine supplementation at pharmacological doses. Despite...     

Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia

Background

Recessive LPIN1 mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin-2 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the LPIN family genes in a cohort of pediatric and adult patients (n?=?171) presenting with muscular symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L) rhabdomyolysis (n?=?141) to exercise-induced myalgia (n?=?30), and to report the clinical findings in patients harboring mutations.

Methods

Coding regions of LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs.

Results

Eighteen patients harbored two LPIN1 mutations, including a frequent intragenic deletion. All presented with severe episodes of rhabdomyolysis, starting before age 6 years except two (8 and 42 years). Few patients also suffered from permanent muscle symptoms, including the eldest ones (≥40 years). Around 3/4 of muscle biopsies showed accumulation of lipid droplets. At least 40% of heterozygous relatives presented muscular myalgia. Nine heterozygous SNPs in LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non-functional in yeast complementation assay based on respiratory activity, except the LPIN3-P24L variant.

Conclusion

LPIN1-related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscular manifestations.     

Fatal rhabdomyolysis in 2 children with LPIN1 mutations

We report 2 cases of fatal rhabdomyolysis in children carrying an LPIN1 mutations preceded by similar electrocardiogram changes, including diffuse symmetrical high-amplitude T waves. Our report underlines the severity of this disease and the need for active management of episodes of rhabdomyolysis in a pediatric intensive care unit.     

Collision lung tumor associating typical carcinoid tumor to sclerosing hemangioma

Collision tumors associating carcinoid tumor and sclerosing pneumocytoma have rarely been reported in the literature. The clinical presentation may be challenging especially in cases showing multiple and bilateral nodules. This case illustrates the association of both tumors diagnosed incidentally and illustrates a full spectrum of neuroendocrine lesions and sclerosing pneumocytoma. The authors present the case of a 52‐year‐old patient presenting an abdominal pain revealing a vesicular lithiasis and multiple pulmonary nodules. Radiologic follow‐up of the asymptomatic lung lesions revealed the stabilization of a left lobe lesion with a disappearance of the other lesions. A lobectomy with a mediastinal lymph node curettage was performed. The microscopic examination revealed both tumor components associating a typical carcinoid tumor to a sclerosing pneumocytoma in association to lesions of diffuse neuroendocrine hyperplasia present in the peri‐tumoral parenchyma. This case illustrates radiologic, gross, and microscopic features of a rare pulmonary tumor.