1. LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy
- Author
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Philippe Major, Inge A. Meijer, Grant A. Mitchell, Catalina Maftei, Florin Sasarman, Catherine Brunel-Guitton, Elsa Rossignol, and Michel Vanasse
- Subjects
medicine.medical_specialty ,Case Report ,Biology ,medicine.disease_cause ,Rhabdomyolysis ,Frameshift mutation ,Exon ,Endocrinology ,Internal medicine ,Genetics ,medicine ,PA, phosphatidic acid ,Creatine kinase ,lcsh:QH301-705.5 ,Molecular Biology ,Dexamethasone ,UPD, uniparental disomy ,lcsh:R5-920 ,Mutation ,aCGH, array comparative genomic hybridization ,Lipin-1 ,Uniparental disomy ,Chromosome 2 ,medicine.disease ,Treatment ,lcsh:Biology (General) ,Uniparental Isodisomy ,biology.protein ,lcsh:Medicine (General) ,DAG, diacylglycerol ,LPIN1 ,CK, creatine kinase ,medicine.drug - Abstract
Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from the age of 4 years. Analysis of the LPIN1 gene that encodes lipin-1 revealed a novel homozygous frameshift mutation in exon 9, c.1381delC (p.Leu461SerfsX47), and complete uniparental isodisomy of maternal chromosome 2. This mutation is predicted to cause complete lipin-1 deficiency. The patient had six rhabdomyolytic crises, with creatine kinase (CK) levels up to 300,000 U/L (normal, 30 to 200). Plasma CK remained elevated between crises. A treatment protocol was instituted, with early aggressive monitoring, hydration, electrolyte replacement and high caloric, high carbohydrate intake. The patient received dexamethasone during two crises, which was well-tolerated and in these episodes, peak CK values were lower than in preceding episodes. Studies of anti-inflammatory therapy may be indicated in lipin-1 deficiency.
- Published
- 2015