Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG),Genetics in Medicine

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Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)
Genetics in Medicine ( IF 6.6 ) Pub Date : 2019-01-19 , DOI: 10.1038/s41436-018-0364-2
Priya S Kishnani ₁ , Jennifer Goldstein ₂ , Stephanie L Austin ₁ , Pamela Arn ₃ , Bert Bachrach ₄ , Deeksha S Bali ₁ , Wendy K Chung ₅ , Areeg El-Gharbawy ₆ , Laurie M Brown ₇ , Stephen Kahler ₈ , Surekha Pendyal ₁ , Katalin M Ross ₉ , Laurie Tsilianidis ₁₀ , David A Weinstein ₁₁ , Michael S Watson ₁₂ ,

Affiliation

Duke University School of Medicine, Durham, NC, USA.
University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Nemours Children's Clinic, Jacksonville, FL, USA.
University of Missouri Health System, Columbia, MO, USA.
Columbia University Medical Center, New York, NY, USA.
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
University of Florida College of Medicine, Gainesville, FL, USA.
Arkansas Children's Hospital, Little Rock, AR, USA.
Connecticut Children's Medical Center, Hartford, CT, USA.
Cleveland Clinic, Cleveland, OH, USA.
University of Connecticut School of Medicine, Connecticut Children's Hospital, Hartford, CT, USA.
American College of Medical Genetics and Genomics, Bethesda, MD, USA.

Purpose

Glycogen storage disease (GSD) types VI and IX are rare diseases of variable clinical severity affecting primarily the liver. GSD VI is caused by deficient activity of hepatic glycogen phosphorylase, an enzyme encoded by the PYGL gene. GSD IX is caused by deficient activity of phosphorylase kinase (PhK), the enzyme subunits of which are encoded by various genes: ɑ (PHKA1, PHKA2), β (PHKB), ɣ (PHKG1, PHKG2), and δ (CALM1, CALM2, CALM3). Glycogen storage disease types VI and IX have a wide spectrum of clinical manifestations and often cannot be distinguished from each other, or from other liver GSDs, on clinical presentation alone. Individuals with GSDs VI and IX can present with hepatomegaly with elevated serum transaminases, ketotic hypoglycemia, hyperlipidemia, and poor growth. This guideline for the management of GSDs VI and IX was developed as an educational resource for health-care providers to facilitate prompt and accurate diagnosis and appropriate management of patients.

Methods

A national group of experts in various aspects of GSDs VI and IX met to review the limited evidence base from the scientific literature and provided their expert opinions. Consensus was developed in each area of diagnosis, treatment, and management. Evidence bases for these rare disorders are largely based on expert opinion, particularly when targeted therapeutics that have to clear the US Food and Drug Administration (FDA) remain unavailable.

Results

This management guideline specifically addresses evaluation and diagnosis across multiple organ systems involved in GSDs VI and IX. Conditions to consider in a differential diagnosis stemming from presenting features and diagnostic algorithms are discussed. Aspects of diagnostic evaluation and nutritional and medical management, including care coordination, genetic counseling, and prenatal diagnosis are addressed.

Conclusion

A guideline that will facilitate the accurate diagnosis and optimal management of patients with GSDs VI and IX was developed. This guideline will help health-care providers recognize patients with GSDs VI and IX, expedite diagnosis, and minimize adverse sequelae from delayed diagnosis and inappropriate management. It will also help identify gaps in scientific knowledge that exist today and suggest future studies.

中文翻译：

VI 型和 IX 型糖原贮积病的诊断和管理：美国医学遗传学和基因组学学院 (ACMG) 的临床实践资源

目的

糖原贮积病 (GSD) VI 型和 IX 型是临床严重程度不同的罕见疾病，主要影响肝脏。GSD VI 是由肝糖原磷酸化酶（一种由PYGL基因编码的酶）活性不足引起的。GSD IX 是由磷酸化酶激酶 (PhK) 活性不足引起的，其酶亚基由多种基因编码：ɑ ( PHKA1 , PHKA2 ), β ( PHKB ), ɣ ( PHKG1 , PHKG2 ) 和δ ( CALM1 , CALM2 ) ,平静3）。VI 型和 IX 型糖原贮积病具有广泛的临床表现，仅凭临床表现通常无法相互区分或与其他肝脏 GSD 区分开来。GSD VI 和 IX 患者可出现肝肿大，伴有血清转氨酶升高、酮症性低血糖、高脂血症和生长不良。该 GSD VI 和 IX 管理指南是作为医疗保健提供者的教育资源而制定的，以促进迅速和准确的诊断以及对患者的适当管理。