A Japanese Patient With Cardiomyopathy Caused by a Novel Mutation R285X in the AGL Gene

Ogimoto, Akiyoshi; Okubo, Minoru; Okayama, Hideki; Shin, Yoon S.; Endo, Yoriko; Ebara, Tetsu; Inoue, Kentaro; Ohtsuka, Tomoaki; Tahara, Hideki; Higaki, J.

doi:10.1253/circj.71.1653

Cited by 9 publications

(3 citation statements)

References 23 publications

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“…Given that diastolic dysfunction is often the first functional abnormality in hypertrophic cardiomyopathy, it usually precedes any systolic dysfunction. There is one case report 79 that notes echo parameters suggesting LV diastolic dysfunction in the face of preserved systolic function with normal ejection fraction. Furthermore, longitudinal follow-up of GSD III patients with respect to cardiac involvement has not been reported; however, in this journal, a recent study is included with longitudinal follow-up and LV mass and wall thickness measurements.…”

Section: Laboratory Diagnostic Testing Recommendationsmentioning

confidence: 99%

Glycogen Storage Disease Type III diagnosis and management guidelines

Kishnani

Austin

Arn

et al. 2010

Genetics in Medicine

249

282

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Section: Laboratory Diagnostic Testing Recommendationsmentioning

confidence: 99%

Glycogen Storage Disease Type III diagnosis and management guidelines

Kishnani

Austin

Arn

et al. 2010

Genetics in Medicine

249

282

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“…Some studies describe severe hepatopathy at older ages in patients with GSD III, such as in the second decade of life in an 18-year-old patient with the genotype c.2607_2610delATCC/c.1672dupA [ 24 ] or in the third decade in 16% of the patients reported [ 9 ]. The cardiomyopathy is also reported later, in adult life [ 25 ]. The phenotype in our patient with early hepatic and cardiac damage may be explained by the fact that both mutations generate premature stop codons, with the theoretical risk of null alleles for the development of a more severe clinical picture [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Nonsense Mutation of the AGL Gene in a Romanian Patient with Glycogen Storage Disease Type IIIa

Zimmermann

Rossmann

Bucerzan³

et al. 2016

Case Reports in Genetics

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Background. Glycogen storage disease type III (GSDIII) is a rare metabolic disorder with autosomal recessive inheritance, caused by deficiency of the glycogen debranching enzyme. There is a high phenotypic variability due to different mutations in the AGL gene. Methods and Results. We describe a 2.3-year-old boy from a nonconsanguineous Romanian family, who presented with severe hepatomegaly with fibrosis, mild muscle weakness, cardiomyopathy, ketotic fasting hypoglycemia, increased transaminases, creatine phosphokinase, and combined hyperlipoproteinemia. GSD type IIIa was suspected. Accordingly, genomic DNA of the index patient was analyzed by next generation sequencing of the AGL gene. For confirmation of the two mutations found, genetic analysis of the parents and grandparents was also performed. The patient was compound heterozygous for the novel mutation c.3235C>T, p.Gln1079⁎ (exon 24) and the known mutation c.1589C>G, p.Ser530⁎ (exon 12). c.3235 >T, p.Gln1079⁎ was inherited from the father, who inherited it from his mother. c.1589C>G, p.Ser530⁎ was inherited from the mother, who inherited it from her father. Conclusion. We report the first genetically confirmed case of a Romanian patient with GSDIIIa. We detected a compound heterozygous genotype with a novel mutation, in the context of a severe hepatopathy and an early onset of cardiomyopathy.

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“…Long‐term complications, however, are different between the two GSD types. GSD IIIa involves cardiomyopathy, 3 liver cirrhosis, and hepatocellular carcinoma, 4 while gout, hepatic adenomas, osteoporosis, and renal disease are present in patients with GSD Ia. Clear differential diagnosis of the two hepatic GSD requires both an enzymatic and a molecular assessment.…”

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confidence: 99%

Novel AGL mutation in a Turkish patient with glycogen storage disease type IIIa

Aoyama

Endo

Ebara

et al. 2010

Pediatrics International

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Key words AGL, deletion, glycogen debranching enzyme, glycogen storage disease type IIIa, Turkey.Glycogen storage diseases (GSD) are heterogeneous groups of inborn errors of glycogen metabolism and are divided into several types based on deficient enzymes. 1,2 Glycogen is metabolized by glycogen phosphorylase and glycogen debranching enzyme (GDE). GDE is a single protein with two independent catalytic activities: oligo-1, 4-1, 4 glucantransferase (EC 2.4.1.25) and amylo-1, 6-glucosidase (AGL) (EC 3.2.1.33). The gene encoding GDE is designated as the AGL gene. Deficiency of GDE is GSD type III (GSD III; OMIM 232400), an autosomal recessive inherited disorder. The disease is characterized by fasting hypoglycemia, growth retardation, and hepatomegaly. Most GSD III patients are GDE deficient in both liver and muscle (type IIIa) and present muscle weakness in adulthood, whereas 15% of patients have GDE absent in liver but present in muscle tissue (type IIIb) and do not show any muscular symptoms. These clinical manifestations are almost indistinguishable from those in GSD type Ia (OMIM 232200), glucose-6-phosphatase deficiency. Long-term complications, however, are different between the two GSD types. GSD IIIa involves cardiomyopathy, 3 liver cirrhosis, and hepatocellular carcinoma, 4 while gout, hepatic adenomas, osteoporosis, and renal disease are present in patients with GSD Ia. Clear differential diagnosis of the two hepatic GSD requires both an enzymatic and a molecular assessment.Here, we present a patient with GSD IIIa who was referred to Istanbul University Hospital as having GSD Ia, and describe a novel AGL mutation in this patient of Turkish ancestry. Case reportThe present patient was an 11-year-old Turkish boy. He was born at full term and hepatomegaly was noticed at the age of 7 months. A liver biopsy, performed in a hospital in Turkey at the age of 1 year, showed elevated glycogen content, enlarged hepatocytes with glycogen, and mild portal fibrosis. He was then diagnosed as having 'GSD Ia' and had been on dietary therapy with corn starch to prevent hypoglycemia.The patient was referred to Istanbul University when he was 3 1 /2 years old. At the first evaluation he had short stature (height 86 cm, <3rd percentile), a doll-like face, hepatomegaly, and splenomegaly. Laboratory data showed elevated liver enzymes (aspartate aminotransferase, 718 IU/L; alanine aminotransferase, 333 IU/L), hypercholesterolemia (total cholesterol, 278 mg/dL), and hypertriglyceridemia (triglyceride, 665 mg/dL). The patient had chronic hypochromic normocytic anemia (hemoglobin, 8.8 g/dL), which gradually resolved. His plasma lactate level fluctuated between 63.1 and 7.2 mg/dL (normal range, <19.8 mg/ dL). In contrast, fasting plasma glucose, uric acid, and creatine phosphokinase (CPK) levels were within normal range (106 mg/ dL, 3.6 mg/dL, and 49 IU/L, respectively). An echocardiogram was normal at that time.Diagnosis of 'GSD Ia' in the patient did not fit the clinical data: he had higher liver enzymes and glucose levels and lowe...

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A Japanese Patient With Cardiomyopathy Caused by a Novel Mutation R285X in the AGL Gene

Cited by 9 publications

References 23 publications

Glycogen Storage Disease Type III diagnosis and management guidelines

Glycogen Storage Disease Type III diagnosis and management guidelines

A Novel Nonsense Mutation of the AGL Gene in a Romanian Patient with Glycogen Storage Disease Type IIIa

Novel AGL mutation in a Turkish patient with glycogen storage disease type IIIa

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