Case reportFirst presentation of LPIN1 acute rhabdomyolysis in adolescence and adulthood
Introduction
Lipin-1 (LPIN1) is an 890 aminoacid intracellular protein involved in different pathways of fatty acid metabolism [1]. It belongs to the family of phosphatidate phosphatase (PAP) enzymes and its main role is to catalyse the conversion of phosphatidate to diacylglycerol, the penultimate step of triglyceride synthesis which constitute the major energy storage in our body [2].
In humans, LPIN1 is mainly expressed in skeletal muscles and adipose tissue but lower levels have been found in the gastrointestinal tract as well [3].
LPIN1 mutations are a known cause of autosomal recessive, recurrent and life-threatening acute rhabdomyolysis of childhood-onset. The first description dates back to 2008 [4]. Since then, other cases have been described in the literature [5,6] and LPIN1 mutations are now considered the second most common cause of early-onset acute rhabdomyolysis, after primary fatty acid oxidation defects [5]. The episodes are usually triggered by fever, fasting or general anaesthesia [7] and the outcome is severe with death in 1/3 of patients [5]. Clinically patients present with episodes characterised by myalgia and myoglobinuria; creatine kinase (CK) increases over 100,000 UI/L but can reach 1 × 106 UI/L. Between episodes, clinical examination, CK and acyl-carnitine profile are usually normal [7].
To our knowledge, there has only been two reports of two individuals presenting with adult-onset rhabdomyolysis [6,8]. We describe two cases of LPIN1 mutation with a milder phenotype presenting in adolescence and adulthood respectively. Our aim is to highlight the importance of looking for LPIN1 mutations in adults presenting with acute rhabdomyolysis.
Section snippets
Case report
Case 1: An 11-year-old Caucasian girl of British origin presented to A&E with diffuse muscle pain, swelling and brown coloured urine. Her CK was 560,000 IU/L. At first, an inflammatory cause was suspected as there were no apparent precipitating factors such as exercise, infection, fasting or general anaesthesia. The autoimmune screening was negative but she was later found to have positive serology indicating Parvovirus infection despite a lack of fever. Six months later she presented with the
Discussion
LPIN1 is a known cause of rhabdomyolysis in early childhood. According to literature, the first episode of rhabdomyolysis usually happens at a mean age of 21 months and in nearly all cases before the age of 5[5]. Here we present two cases, the first one with onset in adolescence (11 years old) and the second one in adulthood (40 years old).
LPIN1 protein is encoded by the LPIN1 gene located in chromosome 2p25.1 and contains 20 exons [9]. Over 25 mutations in LPIN1 gene has been described so far
Acknowledgments
Suzanne English, Martin D Curran, Ruchi Arora, GL Briars, Robert Fincham, Graham Gatward, Hamid Jalal, Andrew Dean, Hongyi Zhang, Sami Al Baba, Mandy Nesbitt and Richard Kirk.
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Two tales of LPIN1 deficiency: from fatal rhabdomyolysis to favorable outcome of acute compartment syndrome
2022, Neuromuscular DisordersCitation Excerpt :Literature cohort showed that the median age at the first episode, and diagnosis was 25 months, and 6 years, respectively, with 1–10 acute attacks before diagnosis. LPIN1 deficiency is also described in adulthood [14,15]. Eight out of 73 patients in the literature were adults (Supplement-1).
Phenotype and genotype of 197 British patients with McArdle disease: An observational single-centre study
2021, Journal of Inherited Metabolic DiseaseA Metabolism Perspective on Pediatric Rhabdomyolysis
2021, Trends in Pediatrics