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

Abstract

Background Lipin-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 presentations Here 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. Conclusions LPIN1-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.

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

“…There were 32 cases with homozygous variants (32/56 57.1%) and 24 cases with compound heterozygous variants (24/56 42.9%). There were 6 variant points in Chinese patients, all of which were compound heterozygous variants; c.2047A > G(p.I683V), c.2107_2108 insAGG(p.Q703delin sQE), c.2428C > T(p.Arg810Cys) and c.1949_1967dupGTGTCACCACGCAGTACCA (p.Gly657CysfsX12) were only detected in individuals of Chinese ethnicity ([ 15 , 16 ], our case), and these might be Chinese ethnicity-specific variants.…”

“…The peak CK level was often greater than 10*10 4 U/L. In 40 cases, potential trigger factors had been reported, among which fever was the most common (26/40 65.0%) ([ 4 , 6 , 11 , 13 , 15 , 16 , 20 , 22 ], our case), followed by infection (12/40 30.0%) [ 11 , 13 – 16 , 19 – 21 ], fasting (7/40 17.5%) [ 4 , 16 ], anaesthesia (5/40 12.5%) [ 4 , 14 ], and exercise or physical activity (4/40 10.0%) [ 11 , 14 , 16 , 17 ]. Only 9 cases (9/57 15.8%) [ 6 , 9 , 11 , 13 , 17 – 19 , 22 ] underwent muscle biopsy, which is an invasive procedure that seems to be unpopular.…”

“…The LPIN1 gene is located on chromosome 2p25.1 with two highly conserved domains: the N-terminal LPIN (N-LIP) region spans the first 108 residues, and the C-terminal LPIN (C-LIP) domain consists of 624–830 amino acids. The C-LIP domain contains two key domains: the PAP catalytic motif Asp-Xaa-Asp-Xaa-Thr (DXDXT (689–693)) and the transcriptional coactivator motif Leu-Xaa-Xaa-Ile-Leu (LXXIL (678–682)) [ 16 , 26 ]. They both play an important role in the activity of PAP.…”

“…We searched the PubMed database using "acute recurrent rhabdomyolysis" and "LPIN1" as keywords. There were 57 patients (including our case) with complete clinical data who were genetically diagnosed with acute recurrent RM caused by the LPIN1 gene variant [4,6,[9][10][11][12][13][14][15][16][17][18][19][20][21][22]. These patients were reported from 18 different countries, of which only 3 cases were of Chinese ethnicity.…”

“…There were 8 deaths (8/57 14.0%) [4,9,13], suggesting a high mortality rate of this disease. We also summarized the variant points of 56 cases whose genetic results were reported and finally found 38 different variant points [4,6,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] [15,16], our case), and these might be Chinese ethnicity-specific variants.…”