Case report
First presentation of LPIN1 acute rhabdomyolysis in adolescence and adulthood

https://doi.org/10.1016/j.nmd.2020.05.004Get rights and content

Highlights

  • LPIN1 mutations are a cause of recurrent rhabdomyolysis with onset in adolescence and adulthood.

  • Next generation sequencing panels should be used in the investigation of recurrent rhabdomyolysis.

  • Metabolic and viral stressors should be included in the list of possible rhabdomyolysis precipitant.

Abstract

LPIN1 mutations are a known common cause of autosomal recessive, recurrent and life-threatening acute rhabdomyolysis of childhood-onset. The first episode of rhabdomyolysis usually happens in nearly all cases before the age of 5 and death is observed in 1/3 of patients. Here we present two cases of acute rhabdomyolysis with a milder phenotype caused by LPIN1 mutation presenting in adolescence (11 years old) and adulthood (40 years old) after Parvovirus infection and metabolic stress, respectively. In our opinion, the mutation types, epigenetic factors, the environment exposition to triggers or the existence of proteins with a similar structure of LPIN1, may have a role in modulating the onset of rhabdomyolysis. LPIN1 should be included on a panel of genes analysed in the investigation of adult individuals with rhabdomyolysis. Metabolic and viral stressors should be included in the list of possible rhabdomyolysis precipitant.

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.

References (24)

  • C. Michot et al.

    LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood

    Hum Mutat

    (2010)
  • C. Michot et al.

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

    J Inherit Metab Dis

    (2012)
  • Cited by (4)

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