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Detection of compound heterozygous variants in LPIN1 does not necessarily imply pathogenicity in a patient with rhabdomyolysis.

ABSTRACT: In a recent article by Yim et al., a 15-month-old male is described who experienced severe rhabdomyolysis with a creatine-kinase value (CKV) of 127494 U/l one day after intramuscular injection of an unidentified drug by the general practitioner. Rhabdomyolysis was not attributed to this injected drug but to compound heterozygous variants in LPIN1. The study has a number of shortcomings. Triggers of rhabdomyolysis should be unequivocally identified, a more extensive family history should be taken, and previous CKVs should be provided. Functional and biochemical tests should be carried out to confirm or exclude pathogenicity of the LPIN1 variants.

SUBMITTER: Finsterer J

PROVIDER: S-EPMC7429921 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Detection of compound heterozygous variants in LPIN1 does not necessarily imply pathogenicity in a patient with rhabdomyolysis.

Finsterer Josef J Aliyev Rahim R

F1000Research 20200113

In a recent article by Yim et al., a 15-month-old male is described who experienced severe rhabdomyolysis with a creatine-kinase value (CKV) of 127494 U/l one day after intramuscular injection of an unidentified drug by the general practitioner. Rhabdomyolysis was not attributed to this injected drug but to compound heterozygous variants in LPIN1. The study has a number of shortcomings. Triggers of rhabdomyolysis should be unequivocally identified, a more extensive family history should b ...[more]

PMID: 32913636

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A rare case of pediatric recurrent rhabdomyolysis with compound heterogenous variants in the LPIN1.

Project description:BackgroundLipin-1, encoded by LPIN1 gene, serves as an enzyme and a transcriptional co-regulator to regulate lipid metabolism and mitochondrial respiratory chain. Autosomal recessive mutations in LPIN1 were recognized as one of the most common causes of pediatric recurrent rhabdomyolysis in western countries. However, to date, there were only a few cases reported in Asian group. This study aims to report the first pediatric case of recurrent rhabdomyolysis with a novel LPIN1 mutation in China mainland in order to raise the awareness of both pediatricians and patients.Case presentationsHere we report a Chinese pediatric case of recurrent rhabdomyolysis with compound heterozygous variants (p.Arg388* and p.Arg810Cys) in the LPIN1 gene. The c.2428C > T was a novel missense variant involved Arg-to-Cys substitution at position 810 (p.Arg810Cys), located in the highly conserved region which predicted to be damaging by multiple algorithms. The patient manifested as cola-colored urine, muscle weakness and tenderness, as well as acute kidney injury with peak blood creatine kinase level 109,570 U/l in 19-month old. In his second episode of 9 years old, the symtoms were relatively milder with peak creatine kinase level 50,948 U/l. He enjoyed quite normal life between the bouts but slightly elevation of serum creatine kinase level during the fever or long-term exercises. Prolonged weight training combined with calorie deprivation were speculated to be the triggers of his illness. Prompt symptomatic therapy including fluid therapy and nutritional support was given and the patient recovered soon.ConclusionsLPIN1-related rhabdomyolysis is still quite new to physicians due to its seemly low-incidence especially in Asian countries. In the future, more active genetic test strategy and detailed prophylactic care education should be taken in patients with severe recurrent rhabdomyolysis, who are the high risk group of LPIN1 genetic defects.

| S-EPMC7222443 | biostudies-literature

Acute recurrent rhabdomyolysis in a Chinese boy associated with a novel compound heterozygous LPIN1 variant: a case report.

Project description:BackgroundLPIN1-related acute recurrent rhabdomyolysis (RM), first reported in 2008, is an autosomal recessive inherited metabolic disease. In recent years, LPIN1 gene variants have been identified as one of the main causes of severe RM in children in Western countries. The disease is extremely rare in China, and we report a case of acute recurrent RM caused by a novel compound heterozygous LPIN1 variant.Case presentationA 15-year-old Chinese boy presented with myalgia after strenuous exercise, accompanied by transient increases in serum creatine kinase and myoglobin and persistent hyperuricaemia and hyperbilirubinaemia. Genetic analysis using high-throughput genomic sequencing and Sanger sequencing revealed that there was a compound heterozygous variant in the LPIN1 gene of the proband: the paternal c.2047A?>?G(p.I683V) was an unreported missense variant, and the maternal c.2107_2108 insAGG(p.Q703delin sQE) was an unreported in-frame variant.ConclusionsIn children with RM, LPIN1 variants should always be considered in the differential diagnosis. The clinical features of our case are atypical, which highlights the importance of an accurate diagnosis by genetic testing. If detected early, the condition may be controlled, and the prognosis may be improved.

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Intrafamilial Variability in LPIN1-Related Rhabdomyolysis

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Molecular analysis of LPIN1 in Jordanian patients with rhabdomyolysis.

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| S-EPMC5874394 | biostudies-literature

Use of dexamethasone in acute rhabdomyolysis in LPIN1 deficiency.

Project description:IntroductionLPIN1 deficiency is an autosomal recessive form of early childhood recurrent severe rhabdomyolysis. Although not completely lucid yet, LPIN1 has been shown to modulate endosomal-related pro-inflammatory responses via peroxisome proliferator-activated receptor α (PPARα) and PPARγ coactivator 1α (PGC-1α). Treatment with anti-inflammatory agents such as dexamethasone has been proposed to improve the outcome.CaseWe report a male toddler with recurrent episodes of complicated rhabdomyolysis, requiring prolonged intensive care unit admissions. Whole exome sequencing revealed a common homozygous 1.7 kb intragenic deletion in LPIN1. Despite optimal metabolic cares, the patient presented with an extremely high CK level where he benefited from intravenous dexamethasone (0.6 mg/Kg/day) for a period of 6 days.ResultsDexamethasone administration shortened the course of active rhabdomyolysis, intensive care admission and rehabilitation. It also prevented rhabdomyolysis-related complications such as kidney injury and compartment syndrome.ConclusionOur patient showed a favorable response to parenteral dexamethasone, in addition to hyperhydration with IV fluids, sufficient calorie intake, and restricted dietary fat. The improvement with corticosteroids suggests an uncontrolled inflammatory response as the pathophysiology of LPIN1 deficiency.

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Project description:Individuals with LPIN1 deficiency have early recurrent, life-threatening rhabdomyolysis but the full phenotypic spectrum and optimal treatment of the disorder remains unknown. Here we report the clinical details and treatment outcomes of 6 patients from our health system. The average age of presentation in our cohort was 23.8 months ±11.6 months (range 15-46 months). The average number of days for each hospitalization for this cohort is 11.7±13.2 days. Creatinine kinase (CK) levels peak during our care averaged 607,725 units/L (range 157,000-1,100,000 units/L). We observed that aspartate aminotransferase levels paralleled the CK levels in its elevation and resolution (Pearson's correlation R = 0.995); while alanine aminotransferase paralleled the elevation but lagged in the resolution of CK levels (R = 0.728). Unlike historical accounts, in our patient population, rhabdomyolysis was sometimes seen without inciting viral or traumatic events. We also cared for multiple individuals that had received treatment at other centers. This allowed us to compare multiple practice approaches and led to a standardized Care Recommendations.

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