LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy

I A Meijer; F Sasarman; C Maftei; E Rossignol; M Vanasse; P Major; G A Mitchell; C Brunel-Guitton

doi:10.1016/j.ymgmr.2015.10.010

LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy

Mol Genet Metab Rep. 2015 Nov 8:5:85-88. doi: 10.1016/j.ymgmr.2015.10.010. eCollection 2015 Dec.

Authors

I A Meijer¹, F Sasarman², C Maftei³, E Rossignol¹, M Vanasse¹, P Major¹, G A Mitchell³, C Brunel-Guitton^{2

3}

Affiliations

¹ Division of Pediatric Neurology, Department of Pediatrics, Université de Montréal, and CHU Sainte Justine, 3175 Côte Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada.
² Division of Biochemical Genetics Laboratory, Université de Montréal and CHU Sainte Justine, 3175 Côte Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada.
³ Medical Genetics, Department of Pediatrics, Université de Montréal and CHU Sainte Justine, 3175 Côte Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada.

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.

Keywords: CK, creatine kinase; Chromosome 2; Creatine kinase; DAG, diacylglycerol; LPIN1; Lipin-1; PA, phosphatidic acid; Rhabdomyolysis; Treatment; UPD, uniparental disomy; Uniparental disomy; aCGH, array comparative genomic hybridization.

Publication types

Case Reports