Ke Tong1,2,3,4,5, Geng-Sheng Yu6,7,8,9,10. 1. Department of Cardiovascular Disease, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 2. Ministry of Education Key Laboratory of Child Development and Disorders, 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 3. National Clinical Research Center for Child Health and Disorders (Chongqing), 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 4. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 5. Chongqing Key Laboratory of Pediatrics, 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 6. Department of Cardiovascular Disease, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 18883938208@163.com. 7. Ministry of Education Key Laboratory of Child Development and Disorders, 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 18883938208@163.com. 8. National Clinical Research Center for Child Health and Disorders (Chongqing), 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 18883938208@163.com. 9. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 18883938208@163.com. 10. Chongqing Key Laboratory of Pediatrics, 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. 18883938208@163.com.
Abstract
BACKGROUND: LPIN1-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 PRESENTATION: A 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. CONCLUSIONS: In 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.
BACKGROUND:LPIN1-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 PRESENTATION: A 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. CONCLUSIONS: In 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.
Authors: Bernard P C Kok; Tamara D Skene-Arnold; Ji Ling; Matthew G K Benesch; Jay Dewald; Thurl E Harris; Charles F B Holmes; David N Brindley Journal: J Biol Chem Date: 2014-02-20 Impact factor: 5.157
Authors: Sue Richards; Nazneen Aziz; Sherri Bale; David Bick; Soma Das; Julie Gastier-Foster; Wayne W Grody; Madhuri Hegde; Elaine Lyon; Elaine Spector; Karl Voelkerding; Heidi L Rehm Journal: Genet Med Date: 2015-03-05 Impact factor: 8.822