scholarly journals Neurological Involvement in Glycogen Storage Disease Type IXa due to PHKA2 Mutation

2020 ◽  
Vol 47 (3) ◽  
pp. 400-403 ◽  
Author(s):  
Chelsea Smith ◽  
Marie-Josée Dicaire ◽  
Bernard Brais ◽  
Roberta La Piana ◽  
Keyword(s):  
Storage Disease ◽  
Glycogen Synthesis ◽  
Missense Variant ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Regulatory Subunit ◽  
Neurological Involvement ◽  
Phosphorylase Kinase ◽  
Glycogen Storage Diseases ◽  
Whole Exome

ABSTRACT:Glycogen storage diseases (GSDs) result from the deficiency of enzymes involved in glycogen synthesis and breakdown into glucose. Mutations in the gene PHKA2 encoding phosphorylase kinase regulatory subunit alpha 2 have been linked to GSD type IXa. We describe a family with two adult brothers with neonatal hepatosplenomegaly and later onset of hearing loss, cognitive impairment, and cerebellar involvement. Whole-exome sequencing was performed on both subjects and revealed a shared hemizygous missense variant (c.A1561G; p.T521A) in exon 15 of PHKA2. The phenotype broadens the clinical and magnetic resonance imaging spectrum of GSD type IXa to include later onset neurological manifestations.

PHKG2 mutation spectrum in glycogen storage disease type IXc: a case report and review of the literature

2018 ◽  
Vol 31 (3) ◽  
pp. 331-338 ◽  
Author(s):  
Chunyun Li ◽  
Lihua Huang ◽  
Lang Tian ◽  
Jia Chen ◽  
Shentang Li ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Novel Mutation ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Mutation Spectrum ◽  
Chinese Family ◽  
Phosphorylase Kinase

AbstractBackground:PHKG2gene mutation can lead to liver phosphorylase kinase (PhK) deficiency, which is related to glycogen storage disease type IX (GSD IX). GSD IXc due toPHKG2mutation is the second most common GSD IX.Methods:We identified a novel mutation (c.553C>T, p.Arg185X) inPHKG2in a Chinese family and verified it by next-generation and Sanger sequencing. The mutation spectrum of thePHKG2gene was summarized based on 25 GSD IXc patients withPHKG2mutations.Results:We found that missense mutation (39%) was the most common type of mutation, followed by nonsense mutation (23%). Mutations were more prevalent in Asian (12/25) and European (9/25) populations than in populations from elsewhere. The exons had more sites of mutation than the introns, and exons 3 and 6 were the most frequent sites of mutations.Conclusions:This study expands our knowledge of thePHKG2gene mutation spectrum, providing a molecular basis for GSD IXc.

Late presentation of glycogen storage disease types Ia and III in children with short stature and hepatomegaly

2018 ◽  
Vol 31 (4) ◽  
pp. 473-478 ◽  
Author(s):  
David Quackenbush ◽  
Justin Devito ◽  
Luigi Garibaldi ◽  
Melissa Buryk
Keyword(s):  
Short Stature ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Novel Mutation ◽  
Glycogen Synthesis ◽  
Previous History ◽  
Severe Hypoglycemia ◽  
Late Presentation ◽  
Glycogen Storage ◽  
Glycogen Storage Diseases

AbstractBackground:Glycogen storage diseases (GSDs) are a collection of disorders related to glycogen synthesis or degradation that classically present in infancy with hypoglycemia, failure to thrive and hepatomegaly; however, their phenotype can vary significantly.Case presentation:We present the cases of two children, 5 years old and 3.5 years old, who were referred to endocrinology for short stature. They were ultimately found to have hepatomegaly, fasting hypoglycemia, mild elevation of transaminases and ketosis. Laboratory and genetic studies were consistent with double heterozygosity for GSDs Ia and III, with one novel mutation discovered in each patient. Nightly, both children were treated with cornstarch, which resulted in resolution of laboratory abnormalities and improvement in their growth velocity. These cases are unusual in that GSD was diagnosed relatively late in life in patients with no previous history of severe hypoglycemia.Conclusions:They highlight the importance of considering glycogen storage disease in a child presenting with short stature, as it is a treatable disease that can be diagnosed non-invasively with genetic testing.

scholarly journals A founder AGL mutation causing glycogen storage disease type IIIa in Inuit identified through whole-exome sequencing: a case series

2015 ◽  
Vol 187 (2) ◽  
pp. E68-E73 ◽  
Author(s):  
Isabelle Rousseau-Nepton ◽  
Minoru Okubo ◽  
Rosemarie Grabs ◽  
John Mitchell ◽  
Constantin Polychronakos ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Case Series ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type Iiia ◽  
Whole Exome

scholarly journals Whole Exome Sequencing detects PYGM variants in two adults with McArdle disease

2022 ◽  
pp. mcs.a006173
Author(s):  
Amanda Thomas-Wilson ◽  
Avinash V Dharmadhikari ◽  
Jonas J Heymann ◽  
Vaidehi Jobanputra ◽  
Salvatore DiMauro ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Storage Disease ◽  
Missense Variant ◽  
Glycogen Storage ◽  
Exercise Intolerance ◽  
Mcardle Disease ◽  
Whole Exome ◽  
History Of ◽  
In Trans ◽  
The Common

McArdle disease is a progressive and debilitating glycogen storage disease with typical onset in late childhood. Here we describe a former competitive athlete with early adult onset McArdle disease and a septuagenarian with a history of exercise-intolerance since adolescence who was evaluated for proximal muscle weakness. Exome sequencing identified bi-allelic variants in PYGM gene for both cases. The former athlete has the common, well-known pathogenic variant p.(Arg50Ter) in trans with a novel missense variant, p.(Asp694Glu). The second individual has a previously described homozygous missense variant, p.(Arg771Gln). Here, we describe the clinical course, enzyme-testing results using muscle tissue and molecular findings for the individuals, and add to the knowledge of the genotypic spectrum of this disorder.

scholarly journals Identification of p.His119Leu mutation in the G6PC gene of a Vietnamese patient with glycogen storage disease type Ia

2020 ◽  
Vol 42 (2) ◽  
Author(s):  
Nguyen Huy Hoang ◽  
Vu Chi Dung ◽  
Nguyen Van Tung ◽  
Nguyen Ngoc Lan ◽  
Ha Thi Dung
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Whole Exome ◽  
Sequencing Method ◽  
Type Ia ◽  
In Silico Analyses ◽  
Homozygous Form

Glycogen storage disease type Ia (GSD Ia), a rare autosomal inherited disorder, is characterized by accumulation of excessive glycogen and fat in the liver. Primary symptoms of GSD Ia include hypoglycemia; metabolic acidosis; elevated levels of lactate, uric acid and lipids; hepatomagaly and growth retardation. Glycogen storage disease type Ia was caused by mutations in the G6PC gene. In this study, mutations in a Vietnamese patient with glycogen storage disease type Ia were analyzed using the whole exome sequencing method. A missense mutation c.356A>T (p.His119Leu) in the G6PC gene of the patient was identified in exon 3. Genetic analysis confirmed that this mutation was present under homozygous form In-silico analyses using SIFT and Mutation Taster confirmed the damaging effects of this mutations on the function of the proteins. This result enriches knowledge of the G6PC gene mutation spectrum and provides genetic data for further studies on glycogen storage disease type Ia in Viet Nam. 

scholarly journals Renal Calculi as Initial Presenting Symptom of Glycogen Storage Disease (Type 1 A) in Early Infancy

2020 ◽  
Vol 10 (01) ◽  
pp. e45-e47
Author(s):  
Nida Mirza ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Case Reports ◽  
Glycogen Synthesis ◽  
Renal Stones ◽  
Renal Calculi ◽  
Glycogen Storage ◽  
Storage Diseases ◽  
Glycogen Storage Diseases

AbstractGlycogen storage diseases are a group of heterogeneous metabolic disorders that result from a defect in enzymatic pathway of either glycogen synthesis or glycogen degradation. Here we are reporting a case of glycogen storage diseases type 1 with renal stone as initial manifestation of disease at 2 months of age. There were case reports of recurrent renal calculi in older age group with this disease and considered to be arisen due to metabolic derangements. Although the exact mechanism of renal stones in glycogen storage disease is not clear, in this unique case occurrence of renal stones at 2 months of age suggests that the pathogenesis of renal calculi is probably multifactorial or a part of disease.

scholarly journals Neurological Characteristics of Pediatric Glycogen Storage Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Julio Henrique Muzetti ◽  
Daniel Almeida do Valle ◽  
Mara L. S. Ferreira Santos ◽  
Bruno Augusto Telles ◽  
Mara L. Cordeiro
Keyword(s):  
Metabolic Control ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Metabolism ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Type I ◽  
Cross Sectional ◽  
Glycogen Storage Diseases ◽  
Multigene Panel

Glycogen storage diseases (GSD) encompass a group of rare inherited diseases due dysfunction of glycogen metabolism. Hypoglycemia is the most common primary manifestation of GSD, and disturbances in glucose metabolism can cause neurological damage. The aims of this study were to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. A cross-sectional study was conducted with 12 children diagnosed with GSD [Types: Ia (n=5); 1, Ib (n=1); 4, IXa (n=5); and 1, IXb (n=1)]. Genetic testing was conducted for the following genes using multigene panel analysis. The biochemical data and magnetic resonance imaging of the brain presented by the patients were evaluated. The criteria of adequate metabolic control were adopted based on the European Study on Glycogen Storage Disease type I consensus. Pathogenic mutations were identified using multigene panel analyses. The mutations and clinical chronology were related to the disease course and neuroimaging findings. Adequate metabolic control was achieved in 67% of patients (GSD I, 43%; GSD IX, 100%). Fourteen different mutations were detected, and only two co-occurring mutations were observed across families (G6PC c.247C>T and c.1039C>T). Six previously unreported variants were identified (5 PHKA2; 1 PHKB). The proportion of GSD IX was higher in our cohort compared to other studies. Brain imaging abnormalities were more frequent among patients with GSD I, early-symptom onset, longer hospitalization, and inadequate metabolic control. The frequency of mutations was similar to that observed among the North American and European populations. None of the mutations observed in PHKA2 have been described previously. Therefore, current study reports six GSD variants previously unknown, and neurological consequences of GSD I. The principal neurological impact of GSD appeared to be related to inadequate metabolic control, especially hypoglycemia.

scholarly journals A Rare Case of Glycogen Storage Disease Type 1a Presenting with Hemophagocytic Lymphohistiocytosis (HLH)

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Hedyeh Saneifard ◽  
Bibishahin Shamsian ◽  
Marjan Shakiba ◽  
Simin Karizi Zarea ◽  
Ali Sheikhy
Keyword(s):  
Glycogen Storage Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Storage Disease ◽  
Metabolic Diseases ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Recurrent Fever ◽  
Whole Exome ◽  
Life Threatening

Background. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by fever, respiratory distress, massive hepatomegaly, and bicytopenia. It is classified into primary (congenital) and secondary (acquired) types. There are many diseases associated with secondary HLH, but glycogen storage disease is a novel cause of secondary HLH. Case Presentation. In this case, we present a five-month-old female infant with recurrent fever, poor feeding, pallor, and prolonged diarrhea for two months. With a diagnosis of HLH, the patient was treated with IVIG and prednisolone. After treatment was initiated, the patient’s general condition improved. All metabolic workup was normal. We did whole-exome sequencing that confirmed glycogen storage disease (GSD) type 1. Conclusion. Metabolic diseases are one of the severe causes of secondary HLH in infants; hence, complete metabolic assessment is mandatory in these patients, and GSD must be included in the differential diagnosis of HLH metabolic causes.

scholarly journals Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome

2021 ◽  
Vol 11 ◽  
Author(s):  
Maryam Eghbali ◽  
Kiyana Sadat Fatemi ◽  
Shadab Salehpour ◽  
Maryam Abiri ◽  
Hassan Saei ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Genes ◽  
Carrier Status ◽  
Mendelian Disease ◽  
Pathogenic Variants ◽  
Glycogen Storage Diseases ◽  
Whole Exome

Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset.

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