Author:
He Xiufang,Li Xuandi,Lin Yuese,Ba Hongjun,Peng Huimin,Zhang Lili,Zhu Ling,Qin Youzhen,Li Shujuan
Abstract
BackgroundPompe disease is usually considered in children with elevated creatine kinase (CK) levels and decreased acidic α-glucosidase (GAA) enzyme activity. However, there are exceptions, such as GAA pseudo deficiency alleles, which result in lower GAA enzyme activity but do not cause Pompe disease. Here, we report two cases presenting with high CK levels and low GAA activity who were ultimately diagnosed with Duchenne muscular dystrophy (DMD).Case PresentationCase 1 patient was a 2-month-old boy who presented with an extremely high serum CK level (5,480∼11,880 U/L) and low GAA activity (2.72 nmol/1 h/mg). The whole-exome sequencing did not find the pathogenic GAA gene mutation, however, there was a DMD gene hemizygous variation (c. 7657C > T, p. Arg2553Ter) inherited from his mother, which was verified by the first-generation sequencing. Further genetic analysis of GAA identified two homozygous pseudo deficiency alleles (c.1726G > A, p. Gly576Ser and c.2065G > A, p. Glu689Lys), which were believed to induce the patient’s low GAA activity. Therefore, the boy was diagnosed with DMD, although he had extremely low GAA activity. Case 2 patient was also a 2-month-old boy presenting with a significant increase in CK level (12,408∼24,828 U/L). His blood GAA activity (colorimetric method) was 9.02 nmol/1 h/mg. Similarly, his whole-exome sequencing did not find the pathogenic mutation of the GAA gene, but a DMD gene hemizygous variation (c.5571del, p. Lys1857AsnfsTer8), hence he was diagnosed with DMD as well. Regarding GAA activity, the case 2 patient was not as low as the case 1 patient, mainly because his two GAA pseudo deficiency alleles were heterozygous.ConclusionPompe disease is usually screened in infants with high CK levels. We should be aware that pseudo deficiency alleles can cause low GAA activities but not Pompe disease. Genetic tests would be helpful to distinguish cases with GAA pseudo deficiency alleles from patients with some muscular disorder diseases such as DMD.
Funder
National Natural Science Foundation of China
Subject
Pediatrics, Perinatology and Child Health
Reference20 articles.
1. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management.;Birnkrant;Lancet Neurol.,2018
2. Pompe’s disease.;van der Ploeg;Lancet.,2008
3. Genetic heterozygosity and pseudodeficiency in the Pompe disease newborn screening pilot program.;Labrousse;Mol Genet Metab.,2010
4. Duchenne muscular dystrophy.;Duan;Nat Rev Dis Primers.,2021
5. Structural and biochemical studies on Pompe disease and a “pseudodeficiency of acid alpha-glucosidase”.;Tajima;J Hum Genet.,2007
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献