As the disease progresses, liver failure ultimately results, leading to death by the age of 5 unless a liver transplant is performed A non-progressive hepatic form with a similar presentation has also been described 52 , Neuromuscular variants range in onset from in utero presenting perinatally as fetal akinesia deformation sequence FADS to adulthood as adult polyglucosan body disease APBD with wide severity range from perinatal death to mild symptoms Commonly seen features of the neuromuscular variant of disease includes: hypotonia, muscle atrophy, myopathy, cardiomyopathy, central nervous system CNS , and peripheral nerve system PNS dysfunction Liver dysfunction with abnormal coagulation can be non-specific findings and amylopectin like material deposition can be seen in liver, heart, muscle, brain, spinal cord or reduced glycogen branching enzyme GBE activity seen in liver, muscle or leukocyte; but confirmation made by molecular analysis of GBE1 gene Unlike other liver GSDs, GSD4 has no specific treatment.

Early liver transplant is indicated in patients with the classical hepatic form but only in absence of cardiac or CNS disease GSD4 is rare and has autosomal recessive inheritance with mutations in the GBE1 gene on chromosome 3p GSD9B, also known as phosphorylase kinase deficiency of liver and muscle, have predominant hepatomegaly, short stature seen in early childhood and, sometimes in addition, muscle weakness and hypotonia Can be asymptomatic, but hypoglycemia and reduced enzyme activity can be seen.

Diagnosis is mainly confirmed by mutation analysis of the PHKB gene. Symptomatic with prevention of hypoglycemia with hi-protein and complex carbohydrate diet; though there is no specific treatment for muscle disease GSD9B is an autosomal recessive disorder caused by mutations of β subunit of PHKB gene on chromosome 16q GSD0b, also known as muscle glycogen synthase deficiency, is rare and seems to affect muscle mitochondrial structure and function apart from depleted glycogen Known symptoms include muscle fatigue, exercise intolerance, recurrent exertional syncope, hypertrophic cardiomyopathy, sudden cardiac death without cardiomyopathy 55 - Clinical suspicion with molecular analysis of GYS1 gene provides diagnostic confirmation.

Muscle biopsy can show depleted glycogen; oxidative fibers and abnormal mitochondria 55 - No specific treatment, preventive measures, supportive therapy with high protein complex carbohydrates diet may help.

GSD0b is an autosomal recessive disorder caused by mutations of GSY1 gene on chromosome 19q GSD2, also known as Pompe disease or acid maltase deficiency results from impaired lysosomal acid-α-glucosidase GAA function and accumulation of lysosomal glycogen in skeletal, respiratory and cardiac muscle and often considered as lysosomal storage disorder LSD than GSD.

A non-classical infantile form shows slower symptom progression, is less severe with no cardiomyopathy Late-onset Pompe disease childhood, juvenile, and adult forms is often used to describe patients who present after the first year of life with muscle weakness, and hypotonia Clinical suspicion as noted above with characteristic evidence of hypertrophic cardiomyopathy with EKG findings of shortened PR interval and high QRS complexes and elevated CK is seen in the infantile-onset form.

While, proximal myopathy with diaphragmatic weakness is seen in late-onset disease. Elevated blood aminotransferases and CK are common but diagnostic confirmation noted with deficient GAA enzyme activity in lymphocytes, fibroblasts, and muscle or molecular analysis of biallelic GAA gene GAA activity is usually absent in infantile-onset disease or decreased in late-onset disease.

Some genotype—phenotype correlations exist and determined by the type of the mutation 62 , Dried blood spot testing measuring GAA enzyme activity has helped GSD2 to be included in Newborn Screening Evaluation of the CRIM status is important, since CRIM negative status is associated with poor response to ERT and poor prognosis, if immunomodulation is not started early Results of newborn screening in Taiwan demonstrated significant long-term benefits from the early identification and treatment of patients with infantile Pompe disease before symptoms appeared making an argument for its inclusion in newborn screening panels in many states in the U.

and trialed in several countries 65 , Enzyme replacement therapy ERT using human recombinant acid α-glucosidase, the only approved treatment in the US and Europe since , is based on its ability to degrade accumulated lysosomal glycogen and improve cardiac and skeletal muscle function Though, a negative cross reacting immune material CRIM -negative status has high anti-rhGAA IgG antibodies development and resultant reduced ERT therapeutic effect with poor outcomes if not treated early with immunosuppression 65 , If early diagnosis of late-onset disease is made via newborn screening, the question of when to start treatment in an asymptomatic patient is debated.

Improvement in pulmonary function is seen in symptomatic patients with late-onset disease GSD2 is a pan-ethnic autosomal recessive disorder caused by mutations of the GAA gene on chromosome 17q The increasing list of GAA gene pathogenic mutations can be found at www. The estimated prevalence is considered to be 1 in 5, GSD5, also known as McArdle disease results from deficient muscle phosphorylase activity and results in impaired glycogenolysis leading to exercise intolerance, muscle weakness and cramping alleviated by rest, and exercise induced rhabdomyolysis.

A common history of childhood onset exercise intolerance and a wide range of severity and age of onset reported with most serious complication being renal failure from myoglobinuria and rhabdomyolysis. Apart from clinical suspicion, elevated CK, myoglobinuria and renal dysfunction as common biochemical markers with additional non-invasive diagnostic confirmation with molecular analysis of PYGM gene is indicated.

Invasive muscle biopsy with negative muscle phosphorylase activity can help diagnosis too. Oral sucrose loading 30—40 minutes before exercise helps exercise tolerance as exogenous fuel source to help energy gap with lack of endogenous glucose from glycogenolysis and free fatty acids availability until ~10 minutes into exercising Regular exercise of moderate intensity helps maximize circulatory capacity and increase fuel delivery to muscles GSD5 is an autosomal recessive disorder caused by mutations of PYGM gene on chromosome 11q GSD7, also known as Tarui disease results from deficient muscle subunit of phosphofructokinase PFK enzyme as a rate limiting factor, with resultant impaired glycogenolysis and glycolysis.

The classical form is characterized by exercise intolerance, often with rhabdomyolysis , muscle cramps and pain. In some cases jaundice accompanied by increased serum bilirubin, exercise related elevated CK levels, myoglobinuria and myogenic hyperuricemia may also be seen 72 , In addition, three other GSD7 subtypes are late-onset, infantile, and hemolytic.

Late-onset GSD7 typically presents in later life with muscle cramps and myalgias although patients may show increased muscular weakness and fatigability in childhood. Patients with severe infantile form of GSD7 present with hypotonia early after birth and often die within their first year of life.

Arthrogryposis and mental retardation may be present in cases who survived early death. The hemolytic form is characterized by non-spherocytic hemolytic anemia without muscle symptoms GSD7 though clinically similar to GSD5, is different with the absence of a second wind phenomenon and a detrimental, as opposed to beneficial, effect of glucose administration due to impaired fatty acid oxidation in GSD7 Presentations can include hyperbilirubinemia, increased reticulocytes due to the elevation of hemolysis from partial loss of PFK activity in erythrocytes, elevated CK, lactate dehydrogenase, and aspartate transaminase following acute exercise 4.

Non-invasive diagnostic confirmation includes molecular analysis of PFKM gene Muscle biopsy or forearm exercise test showing elevated ammonia but reduced lactate can confirm impaired glycolysis following anaerobic exercise can be supportive.

Symptomatic and preventive with avoiding strenuous exercise, high protein intake during exercise and avoiding exercise related simple sugars as sucrose intake.

GSD7 is an autosomal recessive disorder caused by mutations of the PFKM gene on chromosome 12q GSD9D, also known as muscle phosphorylase kinase deficiency or X-linked muscle glycogenosis results from impaired alpha subunit of the muscle phosphorylase kinase activity, associated with muscle weakness, atrophy, and exercise-induced pain and stiffness, with a variable age at onset, mainly seen in males, though can remain asymptomatic until intense exercise 39 , GSD9D is an X-linked recessive disorder caused by mutations of the PHKA1 gene which encodes the alpha subunit of muscle phosphorylase kinase on chromosome Xq GSD10 also known as PGAMM deficiency results from impaired muscle phosphoglycerate mutase-2 activity essential for conversion of 3-phosphoglycerate to 2-phosphoglycerate during glycolysis and resultant childhood or adolescence presentation of muscle cramping, rhabdomyolysis, and myoglobinuria precipitated by bursts of vigorous exercise Elevated CK, myoglobinuria can be confirmed non-invasively with molecular analysis of PGAM gene Enzymatic assay shows decreased muscle phosphoglycerate mutase-2 activity.

GSD10 is an autosomal recessive disorder caused by mutations of the PGAM2 gene on chromosome 7p Of the 15 cases reported in the medical literature, a founder exon1 null mutation noted in African Americans 76 , GSD11 78 also known as GSDXI results from impaired muscle M isoform of lactate dehydrogenase enzyme essential for interconversion of lactate and pyruvate in muscle glycolysis with resultant fatigue, exertional myoglobinuria and also uterine pain and stiffness during pregnancy and labor Biochemical findings of elevated CK, lactate and myoglobinuria can be confirmed with molecular analysis of LDHA gene.

LDH activity in red blood cells is low or absent. No specific treatment. In pregnant women with GSD11 planned cesarean section can avoid increased risk of dystocia during labor Lactate dehydrogenase A deficiency is an autosomal recessive disorder caused by mutations of the LDHA gene on chromosome 11p The H isoform of LDH is found in the heart and encoded by the lactate dehydrogenase B gene on chromosome 12p Hepatorenal glycogenosis or Fanconi-Bickel Syndrome, listed as MIM , previously also known as GSD XI, is an autosomal recessive disorder with mutations in SLC2A2 gene encoding GLUT2 transporter, affecting glycogen accumulation in liver and kidney, proximal renal tubular dysfunction and defective glucose and galactose utilization GSD12 also known as ALDOA deficiency, results from impaired fructose-1,6-bisphosphate aldolase A activity, essential for interconversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate in glycolysis, with resultant hereditary non-spherocytic hemolytic anemia and myopathy In contrast, overexpression of aldolase A is associated with multiple forms of cancer including squamous cell carcinoma of the lung, hepatocellular, and renal cancer suggestive that increased glycolysis promotes tumor growth in cells Findings of hemolytic anemia, rhabdomyolysis and myoglobinuria can be confirmed with molecular analysis of ALDOA gene.

Red cells enzymatic assay can show decreased activity. No known specific except symptomatic and preventive management of myopathy and hemolytic anemia complications.

GSD12 is a rare autosomal recessive disorder caused by mutations of ALDOA gene on chromosome 16p GSD13, also known as Enolase-beta deficiency results from impaired beta-enolase activity, necessary for interconversion of 2-phosphoglycerate and phosphoenolpyruvate.

The skeletal muscle isozyme impairments present with adult-onset myalgia post exertion, with mildly elevated CK levels 84 to recurrent rhabdomyolysis GSD13 is a rare autosomal recessive disorder caused by mutations of the ENO3 gene on chromosome 17p GSD14, also known as phosphoglucomutase-1 deficiency or congenital disorder of glycosylation type It CDG-1T has wide clinical spectrum with predominantly milder myopathy form or severe form with multisystem involvement and congenital anomalies In a small study, supplementation with up to 1.

GSD14 is a rare autosomal recessive disorder caused by mutations of the PGM1 gene on chromosome 1p GSD15, also known as Glycogenin deficiency results from impaired glycosyltransferase necessary for short glucose polymer formation from UDP-glucose and glycogen formation, leading to depletion of glycogen in skeletal muscle and abnormal glycogen storage in the heart and resultant myopathy, cardiomyopathy and or arrhythmias Molecular analysis of GYG1 gene provides definitive diagnosis.

Low skeletal muscle glycogen or abnormal cardiac muscle glycogen in the heart in patients with cardiomyopathy No known treatment but glucose infusion during exercise showed improved exercise tolerance GSD15 is a rare autosomal recessive disorder caused by mutations of GYG1 gene on chromosome 3q Diagnosed by mutations in LAMP2 gene located on chromosome Xq24, affecting lysosomal associated membrane protein-2 function of hydrolase sequestration and resultant lysosomal autolytic functions; leads to glycogen and autophagic materials accumulation in muscles and presents with cardiomyopathy, skeletal myopathy, intellectual disability, retinopathy or maculopathy in adolescent and younger adult males mostly, and milder presentation in hemizygous females 90 - Is a cardiac phosphorylase kinase deficiency impairing fatty acid oxidation, glycolysis and glucose oxidation in response to energy demands leading to glycogen storage in cardiac muscles; secondary to mutations in PRKAG2 gene and has autosomal dominant inheritance.

Presentations include lethal congenital or early childhood fatal 93 but can present in adolescence with Wolff-Parkinson-White syndrome WPW on EKG with progressive fatal cardiomyopathy; requiring pacemaker or cardiac transplantation.

Is a progressive myoclonic epilepsy with neurodegeneration in mid childhood to adolescent, caused by mutation in the EPM2 gene on chromosome 6q GSDs and glycogenosis defects, though, heterogenous and individually rare; predominantly affect liver, muscles, heart and in rare instance brain from infancy to adulthood.

Heightened clinical suspicion can lead to GSD diagnosis in primary care and in-patient setting. Common laboratory biochemical evaluation or EKG with a timely referral to biochemical geneticist can help GSD diagnosis.

Medical crises in most GSD are preventable with simple nutritional measures and prevention of energy deficiency triggers. Newborn Screening is changing the natural history of Pompe and lessons from ERT management still unfolding. Without a liver transplant, the perinatal neuromuscular and progressive hepatic types of GSD IV have poor prognoses.

Severe liver failure often results in death within the first five years of life. Managing GSD IV and its symptoms requires lifelong monitoring. This involves working with a multidisciplinary team that may include the following healthcare professionals:. If you, your child, or a sibling has this disease, genetic counseling can help you understand your risk of passing it on to your children.

GSD IV describes a group of disorders that result in the formation of damaged glycogen. This disease is caused by a defect in the glycogen branching enzyme GBE1. This interferes with the normal transformation of glycogen into glucose. As a result, the damaged glycogen stays in the liver and other organs.

Liver damage is a common result. There are five varieties or subtypes of this disease, which can vary greatly in symptoms and outcomes. These subtypes vary based on the amount of bad glycogen in the body. There are no proven treatments for any type of glycogen storage disease, but diet can help with disease management.

However, when severe liver damage occurs, a liver transplant may be the only way to prevent death. Being the parent of a child with GSD IV can be devastating because of the poor outcomes that often accompany this diagnosis.

It can also be lonely dealing with this condition as a parent or patient because the condition is so rare. Family and friends may not understand the disease or the challenges that it brings.

You may find help from online or in-person support groups for people with glycogen storage diseases. This can help offset feelings of isolation and frustration that are common when dealing with a rare disease. These groups can often be a source of emotional support, as well as a resource for sharing disease management strategies.

GSD IV can't be prevented because it is an inherited disease. If you have a family member with this disease, genetic testing can determine your risk factors for developing this disease and passing it to your child.

It's important to remember that the presence of a defective gene doesn't always mean that the disease will develop. GSD IV can cause liver damage so severe that a liver transplant is necessary. Heart failure, breathing problems, and nervous system issues can also occur.

Muscle wasting and poor muscle tone can complicate heart and breathing function. The nonprogressive type often has the least severe symptoms. This variety of the disease usually doesn't involve cirrhosis of the liver, a life-threatening problem that occurs with other types.

Additionally, the prognosis is better among people who are diagnosed later in life with any type. Ross KM, Ferrecchia IA, Dahlberg KR, Dambska M, Ryan PT, Weinstein DA.

Dietary management of the glycogen storage diseases: evolution of treatment and ongoing controversies. Adv Nutr. Glycogen storage disease type IV. NORD - National Organization for Rare Disorders, Inc.

Andersen Disease GSD IV. Type IV Glycogen Storage Disease. By Anna Giorgi Anna Zernone Giorgi is a writer who specializes in health and lifestyle topics. Her experience includes over 25 years of writing on health and wellness-related subjects for consumers and medical professionals, in addition to holding positions in healthcare communications.

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Understand audiences through statistics or combinations of data from different sources. Develop and improve services. Use limited data to select content. List of Partners vendors. Rare Diseases. By Anna Giorgi. Medically reviewed by Isabel Casimiro, MD, PhD. Table of Contents View All. Table of Contents.

Types of GSD IV. Frequently Asked Questions. Frequency of GSD IV GSD IV is an extremely rare condition. Types of Liver Disease and How to Treat Them.

How Genetic Disorders Are Inherited. Do You Qualify for a Liver Transplant? Frequently Asked Questions Is GSD IV preventable? Learn More: Genetic Predisposition: What It Is, What It Means for You.

What are common complications of GSD IV? Learn More: What Are the Warning Signs of Liver Failure? What is the least severe form of GSD IV?

If you have a family member with this disease, genetic testing can determine your risk factors for developing this disease and passing it to your child. It's important to remember that the presence of a defective gene doesn't always mean that the disease will develop.

GSD IV can cause liver damage so severe that a liver transplant is necessary. Heart failure, breathing problems, and nervous system issues can also occur. Muscle wasting and poor muscle tone can complicate heart and breathing function. The nonprogressive type often has the least severe symptoms.

This variety of the disease usually doesn't involve cirrhosis of the liver, a life-threatening problem that occurs with other types. Additionally, the prognosis is better among people who are diagnosed later in life with any type.

Ross KM, Ferrecchia IA, Dahlberg KR, Dambska M, Ryan PT, Weinstein DA. Dietary management of the glycogen storage diseases: evolution of treatment and ongoing controversies. Adv Nutr. Glycogen storage disease type IV. NORD - National Organization for Rare Disorders, Inc.

Andersen Disease GSD IV. Type IV Glycogen Storage Disease. By Anna Giorgi Anna Zernone Giorgi is a writer who specializes in health and lifestyle topics. Her experience includes over 25 years of writing on health and wellness-related subjects for consumers and medical professionals, in addition to holding positions in healthcare communications.

Use limited data to select advertising. Create profiles for personalised advertising. Use profiles to select personalised advertising. Create profiles to personalise content. Use profiles to select personalised content.

Measure advertising performance. Measure content performance. Understand audiences through statistics or combinations of data from different sources. Develop and improve services.

Use limited data to select content. List of Partners vendors. Rare Diseases. By Anna Giorgi. Medically reviewed by Isabel Casimiro, MD, PhD.

Table of Contents View All. Table of Contents. Types of GSD IV. Frequently Asked Questions. Frequency of GSD IV GSD IV is an extremely rare condition. Types of Liver Disease and How to Treat Them. How Genetic Disorders Are Inherited. Do You Qualify for a Liver Transplant?

Frequently Asked Questions Is GSD IV preventable? Learn More: Genetic Predisposition: What It Is, What It Means for You. What are common complications of GSD IV? Learn More: What Are the Warning Signs of Liver Failure? Finally, parents of youth with GSD also reported that their children were less able to function independently than healthy children.

Given the complicated medical regimen that these children must maintain and the difficulty that many children have managing a medical regimen independently Drotar, , these results were not surprising.

It is unclear whether these differences result from decreased ability or decreased opportunity to engage in these activities. Perhaps parents of youth with GSD are more restrictive regarding their children's activities, which may be due to concerns about their child's health or self-management of the treatment regimen.

Future studies should examine this question. Some limitations of the present study should be noted. First, the sample was relatively small, which limited our ability to analyze the effects of demographic e. However, given that the estimated prevalence of GSD Types I—IV is only about 0.

Second, the healthy control sample of children was relatively homogeneous with regard to demographic characteristics; though it did not differ significantly from the make-up of the GSD sample. Third, the assessments in this study consisted of solely self-report or parent-proxy-report measures.

Thus, it is possible that the results were influenced by differences in response patterns. Future studies should attempt to incorporate other methods of assessment e. Within these limitations, this study provides preliminary data regarding social, emotional, behavioral, and familial functioning in families of youth with GSD types Ia and Ib.

Given that parents of youth with GSD type I reported significant distress related to caring for their child with a chronic illness, it is likely that these families would benefit from consultation with a pediatric psychologist in order to learn adaptive ways to manage this extra responsibility and monitor psychosocial functioning.

Children with GSD type I would likely benefit from learning ways to modify their participation in certain activities e. In addition, it is possible that parents and their children with GSD type I could benefit from professional assistance in determining appropriate opportunities for the child to participate in activities independently.

This would help to ensure that the parents are not being overly protective and that the youth can grow in developmentally appropriate ways. Google Scholar. Google Preview. Oxford University Press is a department of the University of Oxford.

It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Navbar Search Filter Journal of Pediatric Psychology This issue Child and Adolescent Psychiatry Clinical Child and Adolescent Psychology Books Journals Oxford Academic Mobile Enter search term Search.

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Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Journal Article. Psychosocial Functioning in Youth with Glycogen Storage Disease Type I.

Eric Storch , Eric Storch. Oxford Academic. Mary Keeley. Lisa Merlo. Marni Jacob. Catherine Correia. David Weinstein. Revision received:.

PDF Split View Views. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex.

txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Close Navbar Search Filter Journal of Pediatric Psychology This issue Child and Adolescent Psychiatry Clinical Child and Adolescent Psychology Books Journals Oxford Academic Enter search term Search. adjustment , children , glycogen storage disease , quality of life.

Table I. Descriptive Statistics and Bivariate Analyses of Quality of Life. Group comparison. Open in new tab. Table II. t -test. Effect size CI. CI for means. Table III. Table IV. BSI global distress 5. Google Scholar Google Preview OpenURL Placeholder Text.

Children's loneliness: A comparison of rejected and neglected peer status. Google Scholar Crossref. Search ADS. The psychosocial well-being of children with chronic disease, their parents and siblings: An overview of the research evidence base.

Quality of life in children with psychiatric disorders: Self-, parent, and clinician report. Factors influencing agreement between child self-report and parent proxy-reports on the pediatric quality of life inventory 4. Promoting adherence to medical treatment in chronic childhood illness: Concepts, methods, and interventions.

Impact of late-onset Pompe disease on participation in daily life activities: Evaluation of the Rotterdam handicap scale. Development of a disease-specific disability instrument for Pompe disease. Chronic physical illness and mental health in children. Results from a large-scale population study. Social functioning and peer relationships of adolescents with juvenile fibromyalgia syndrome.

Health-related quality of life in childhood cancer: Discrepancy in parent-child reports. Validation of the pediatric inventory for parents in mothers of children with type 1 diabetes: An examination of parenting stress, anxiety, and childhood psychopathology.

NPT4, a new microsomal phosphate transporter: Mutation analysis in glycogen storage disease type Ic. Disease related stress in parents of obese children: Relations with parental anxiety and childhood psychosocial functioning.

Glycogen storage disease type I: Diagnosis, management, clinical course and outcome. Results of the European Study on glycogen storage disease type I. Guidelines for management of glycogen storage disease type I — European study on glycogen storage disease type I. Categorical service allocation and barriers to care for children with chronic conditions.

Google Scholar PubMed. OpenURL Placeholder Text. Peer rejection, social behavior, andpsychological adjustment in children with juvenile rheumatic disease. Relationships of self-esteem and efficacy to psychological distress in mothers of children with chronic physical illnesses.

The economic impact of chronic pain in adolescence: Methodological considerations and a preliminary costs-of-illness study. They are reported more in males, and considered most common of all GSD9. Though, initially thought to be mild disease 38 ; severe presentations of liver cirrhosis are also reported.

Symptomatic to prevent hypoglycemia with frequent meals and snacks, high protein diet, and complex carbohydrates.

GSD9a has X-linked inheritance with mutations in the PHKA2 gene on chromosome Xp GSD9c results from impaired gamma unit of phosphorylase kinase enzyme function in liver and testis, with early childhood presentations of recurrent hypoglycemia, hepatomegaly progressing to liver cirrhosis and end stage liver disease; apart from motor delay, hepatosplenomegaly, renal tubular damage and muscle weakness Because the gamma subunit contains the catalytic site of the enzyme, GSD9C typically has a more severe phenotype.

In personal experience SK unpublished data , a teenager presented with seizure disorder, microcephaly, intellectual disability, short stature apart from clinical presentations noted above. Apart from clinical presentation noted above, elevated liver enzymes and lactate with severe fasting ketosis in setting of normal triglycerides creatine kinase CK and uric acid can be seen.

Measurement of enzyme activity in liver may help but diagnostic confirmation includes molecular analysis of PHKG2 gene Nutritional approaches to prevent recurrent hypoglycemia with high-protein and complex carbohydrates and symptomatic treatment and management for any hypoglycemia related complications may be helpful.

In personal experience SK unpublished data , teenage presentation of a GSD9c case with liver failure was treated successfully with liver transplantation and at 3-year post transplantation, showed improvement in cognitive abilities in late adolescence, to secure successful vocational training and employment, improved muscle strength, resolution of hepatosplenomegaly and seizures.

GSD9C is an autosomal recessive disorder caused by mutations of the PHKG2 gene which encodes the gamma subunit of phosphorylase kinase on chromosome 16p GSD3, also known as Cori Disease or Forbes disease results from glycogen debrancher enzyme GDE deficiency with impaired glycogen breakdown and abnormal glycogen accumulation, affecting liver, skeletal and cardiac muscles 35 , Muscular symptoms become apparent during and after adolescence though hypertrophic cardiomyopathy seen in younger childhood 43 , As noted above, characteristic findings include fasting hypoglycemia with ketosis, hyperlipidemia, elevated CK, an inverse relationship between a patients age and liver enzymes, lack of lactic acidosis and hyperuricemia 35 , 43 - A diagnosis can be made by mutation analysis of the AGL gene 46 or liver biopsy to detect the enzymatic defect.

Best approaches are nutritional with frequent meals, with high protein content and lesser amounts of UCCS than in GSD1 , or bedtime glycosade helps growth during adolescence Though there are suggestions that a modified Atkins diet improves myopathy symptoms GSD3 has autosomal recessive inheritance, with 58 different reported mutations in the AGL gene on chromosome 1p GSD4, also known as Andersen disease or Brancher deficiency, is a glycogenolysis defect with impaired and few α-1,6-glycosidic bonds along glycogen chain, resulting in abnormal glycogen with limited branch points limited dextran similar to amylopectin or polyglucosan Clinical presentation is variable and historically classified as two hepatic and four neuromuscular forms based upon age of onset and severity More recent studies suggest that GSD4 phenotypes should be considered a continuum of disease as opposed to discreet subtypes 49 , The classical hepatic GSD4 typically presents within 18 months of birth with patients having a failure to thrive, hepatosplenomegaly, and liver cirrhosis As the disease progresses, liver failure ultimately results, leading to death by the age of 5 unless a liver transplant is performed A non-progressive hepatic form with a similar presentation has also been described 52 , Neuromuscular variants range in onset from in utero presenting perinatally as fetal akinesia deformation sequence FADS to adulthood as adult polyglucosan body disease APBD with wide severity range from perinatal death to mild symptoms Commonly seen features of the neuromuscular variant of disease includes: hypotonia, muscle atrophy, myopathy, cardiomyopathy, central nervous system CNS , and peripheral nerve system PNS dysfunction Liver dysfunction with abnormal coagulation can be non-specific findings and amylopectin like material deposition can be seen in liver, heart, muscle, brain, spinal cord or reduced glycogen branching enzyme GBE activity seen in liver, muscle or leukocyte; but confirmation made by molecular analysis of GBE1 gene Unlike other liver GSDs, GSD4 has no specific treatment.

Early liver transplant is indicated in patients with the classical hepatic form but only in absence of cardiac or CNS disease GSD4 is rare and has autosomal recessive inheritance with mutations in the GBE1 gene on chromosome 3p GSD9B, also known as phosphorylase kinase deficiency of liver and muscle, have predominant hepatomegaly, short stature seen in early childhood and, sometimes in addition, muscle weakness and hypotonia Can be asymptomatic, but hypoglycemia and reduced enzyme activity can be seen.

Diagnosis is mainly confirmed by mutation analysis of the PHKB gene. Symptomatic with prevention of hypoglycemia with hi-protein and complex carbohydrate diet; though there is no specific treatment for muscle disease GSD9B is an autosomal recessive disorder caused by mutations of β subunit of PHKB gene on chromosome 16q GSD0b, also known as muscle glycogen synthase deficiency, is rare and seems to affect muscle mitochondrial structure and function apart from depleted glycogen Known symptoms include muscle fatigue, exercise intolerance, recurrent exertional syncope, hypertrophic cardiomyopathy, sudden cardiac death without cardiomyopathy 55 - Clinical suspicion with molecular analysis of GYS1 gene provides diagnostic confirmation.

Muscle biopsy can show depleted glycogen; oxidative fibers and abnormal mitochondria 55 - No specific treatment, preventive measures, supportive therapy with high protein complex carbohydrates diet may help. GSD0b is an autosomal recessive disorder caused by mutations of GSY1 gene on chromosome 19q GSD2, also known as Pompe disease or acid maltase deficiency results from impaired lysosomal acid-α-glucosidase GAA function and accumulation of lysosomal glycogen in skeletal, respiratory and cardiac muscle and often considered as lysosomal storage disorder LSD than GSD.

A non-classical infantile form shows slower symptom progression, is less severe with no cardiomyopathy Late-onset Pompe disease childhood, juvenile, and adult forms is often used to describe patients who present after the first year of life with muscle weakness, and hypotonia Clinical suspicion as noted above with characteristic evidence of hypertrophic cardiomyopathy with EKG findings of shortened PR interval and high QRS complexes and elevated CK is seen in the infantile-onset form.

While, proximal myopathy with diaphragmatic weakness is seen in late-onset disease. Elevated blood aminotransferases and CK are common but diagnostic confirmation noted with deficient GAA enzyme activity in lymphocytes, fibroblasts, and muscle or molecular analysis of biallelic GAA gene GAA activity is usually absent in infantile-onset disease or decreased in late-onset disease.

Some genotype—phenotype correlations exist and determined by the type of the mutation 62 , Dried blood spot testing measuring GAA enzyme activity has helped GSD2 to be included in Newborn Screening Evaluation of the CRIM status is important, since CRIM negative status is associated with poor response to ERT and poor prognosis, if immunomodulation is not started early Results of newborn screening in Taiwan demonstrated significant long-term benefits from the early identification and treatment of patients with infantile Pompe disease before symptoms appeared making an argument for its inclusion in newborn screening panels in many states in the U.

and trialed in several countries 65 , Enzyme replacement therapy ERT using human recombinant acid α-glucosidase, the only approved treatment in the US and Europe since , is based on its ability to degrade accumulated lysosomal glycogen and improve cardiac and skeletal muscle function Though, a negative cross reacting immune material CRIM -negative status has high anti-rhGAA IgG antibodies development and resultant reduced ERT therapeutic effect with poor outcomes if not treated early with immunosuppression 65 , If early diagnosis of late-onset disease is made via newborn screening, the question of when to start treatment in an asymptomatic patient is debated.

Improvement in pulmonary function is seen in symptomatic patients with late-onset disease GSD2 is a pan-ethnic autosomal recessive disorder caused by mutations of the GAA gene on chromosome 17q The increasing list of GAA gene pathogenic mutations can be found at www.

The estimated prevalence is considered to be 1 in 5, GSD5, also known as McArdle disease results from deficient muscle phosphorylase activity and results in impaired glycogenolysis leading to exercise intolerance, muscle weakness and cramping alleviated by rest, and exercise induced rhabdomyolysis.

A common history of childhood onset exercise intolerance and a wide range of severity and age of onset reported with most serious complication being renal failure from myoglobinuria and rhabdomyolysis. Apart from clinical suspicion, elevated CK, myoglobinuria and renal dysfunction as common biochemical markers with additional non-invasive diagnostic confirmation with molecular analysis of PYGM gene is indicated.

Invasive muscle biopsy with negative muscle phosphorylase activity can help diagnosis too. Oral sucrose loading 30—40 minutes before exercise helps exercise tolerance as exogenous fuel source to help energy gap with lack of endogenous glucose from glycogenolysis and free fatty acids availability until ~10 minutes into exercising Regular exercise of moderate intensity helps maximize circulatory capacity and increase fuel delivery to muscles

Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions.

Close Navbar Search Filter Journal of Pediatric Psychology This issue Child and Adolescent Psychiatry Clinical Child and Adolescent Psychology Books Journals Oxford Academic Enter search term Search.

adjustment , children , glycogen storage disease , quality of life. Table I. Descriptive Statistics and Bivariate Analyses of Quality of Life. Group comparison. Open in new tab. Table II.

t -test. Effect size CI. CI for means. Table III. Table IV. BSI global distress 5. Google Scholar Google Preview OpenURL Placeholder Text. Children's loneliness: A comparison of rejected and neglected peer status. Google Scholar Crossref. Search ADS. The psychosocial well-being of children with chronic disease, their parents and siblings: An overview of the research evidence base.

Quality of life in children with psychiatric disorders: Self-, parent, and clinician report. Factors influencing agreement between child self-report and parent proxy-reports on the pediatric quality of life inventory 4. Promoting adherence to medical treatment in chronic childhood illness: Concepts, methods, and interventions.

Impact of late-onset Pompe disease on participation in daily life activities: Evaluation of the Rotterdam handicap scale. Development of a disease-specific disability instrument for Pompe disease. Chronic physical illness and mental health in children.

Results from a large-scale population study. Social functioning and peer relationships of adolescents with juvenile fibromyalgia syndrome. Health-related quality of life in childhood cancer: Discrepancy in parent-child reports. Validation of the pediatric inventory for parents in mothers of children with type 1 diabetes: An examination of parenting stress, anxiety, and childhood psychopathology.

NPT4, a new microsomal phosphate transporter: Mutation analysis in glycogen storage disease type Ic. Disease related stress in parents of obese children: Relations with parental anxiety and childhood psychosocial functioning.

Glycogen storage disease type I: Diagnosis, management, clinical course and outcome. Results of the European Study on glycogen storage disease type I. Guidelines for management of glycogen storage disease type I — European study on glycogen storage disease type I.

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This Feature Is Available To Subscribers Only Sign In or Create an Account. Instead of having an invasive biopsy, most people can receive molecular genetic testing to accurately determine whether the genes that trigger this condition are abnormal.

This type of testing can also identify carriers and a prenatal diagnosis. Exome sequencing , a type of genetic testing that identifies changes in your genes, can also be used to diagnose this disease. There is no proven treatment or cure for GSD I. However, the disease can be managed with dietary therapy.

This requires following special diet designed to keep glucose levels normal, avoid hypoglycemia, and promote normal growth and development.

Infants are fed soy-based, sugar-free formula on demand every two to three hours. As the infant sleeps longer, they must be awakened every three to four hours for feeding and blood glucose monitoring.

Depending on the child's condition and their healthcare provider's advice, dietary changes to manage this disease can include the following:. These dietary changes are intended to prevent acute and long-term complications, achieve normal psychological development, and improve quality of life.

They must be maintained throughout an affected person's lifetime to benefit from their effects on the disease. Early diagnosis and treatment with dietary therapy can help people who have GSD I experience normal growth and puberty.

Making advised dietary changes can also prevent hypoglycemia and other symptoms and improve life expectancy. Many people who have this disease enjoy normal lifestyles and live into adulthood. People with this condition also have successful pregnancies and childbirths. Treating the condition and maintaining ongoing monitoring can help reduce the risk of developing the following complications:.

Successful management of GSD I includes ongoing care and monitoring by a metabolic team. This typically includes the following healthcare professionals:. Having this condition also requires home blood glucose monitoring using a glucometer or continuous glucose monitoring to assess for hypoglycemia and hyperglycemia.

GSD I causes problems with the body's ability to control the amount of glycogen it stores. It is often found in infants by 6 months of age, when symptoms of hypoglycemia occur.

This disease allows too much glycogen to remain in the liver and kidneys. It also prevents the release of glucose to the rest of the body. The result harms cells and raises the risk of organ and tissue problems in the rest of the body. While there is no proven treatment or cure for this condition, dietary changes and glucose monitoring can improve outcomes.

These steps can aid in quality of life, extend the length of life, and reduce the risk of other health problems. Early diagnosis and treatment have improved the prognosis and outcomes for people with GSD I.

This disease can be managed with the support of a specialized healthcare team. Lifetime dietary therapy and glucose monitoring can help you achieve the best outcomes for you or your affected child.

Educating yourself and your affected children about the condition and dietary restrictions can reduce early symptoms and the risk of complications. While no medical treatment exists, gene therapies in mice models have shown promising results for the potential of future trials in humans.

Babies who have a family member with the disease have a risk of getting it. GSD I is passed from parent to child. A child must inherit a damaged gene from both parents for the disease to occur.

There is no way to prevent this disease. If you or your partner have this disease or a family history of it, it is important to seek genetic counseling prior to pregnancy.

This can identify your risk of having a child with the condition. Early detection, treatment, and monitoring of blood sugar levels can help children with this disease have normal physical and cognitive development.

People with this disease can live normal lives when they maintain advised treatment and monitoring. Ross KM, Ferrecchia IA, Dahlberg KR, Dambska M, Ryan PT, Weinstein DA. Dietary management of the glycogen storage diseases: evolution of treatment and ongoing controversies. Adv Nutr. NORD - National Organization of Rare Disorders, Inc.

Glycogen storage disease type I. People who carry an autosomal recessive trait don't have symptoms of the disease.

However, they can pass it on to their child if the child's other parent has the same autosomal recessive trait. Defects in the GBE1 gene cause GSD IV. The severity of the disease depends on the amount of defective versus functional glycogen that is produced.

There is no specific diagnostic test for GSD IV. Most people with this disease are diagnosed during infancy or childhood, though some people may not be diagnosed until adulthood. A diagnosis of this disease requires one or more laboratory tests that identify certain abnormalities common with this disorder.

This includes the following tests:. With so much variation in symptoms and progression of GSD IV, there is no standard treatment. Treatment is based on addressing each individual's symptoms. Currently, there is no cure for GSD IV. Like other glycogen storage diseases, treatment for this condition usually involves following a specific diet to maintain normal levels of glucose in the blood and improve liver function and muscular strength.

Liver transplantation for the treatment of progressive liver failure has been effective for some patients. Heart transplantation may be necessary when heart damage is severe. Medication may be necessary to treat heart conditions like cardiomyopathy.

Physical therapy can help counter the effects of muscle symptoms like myopathy or hypertonia. GSD IV is a progressive disease in which the liver, muscles, and heart experience increasing damage.

The prognosis differs based on the variety of this disease and its progression. Generally, the later onset of the disease aligns with less severe variations and better outcomes. Without a liver transplant, the perinatal neuromuscular and progressive hepatic types of GSD IV have poor prognoses.

Severe liver failure often results in death within the first five years of life. Managing GSD IV and its symptoms requires lifelong monitoring. This involves working with a multidisciplinary team that may include the following healthcare professionals:.

If you, your child, or a sibling has this disease, genetic counseling can help you understand your risk of passing it on to your children. GSD IV describes a group of disorders that result in the formation of damaged glycogen.

This disease is caused by a defect in the glycogen branching enzyme GBE1. This interferes with the normal transformation of glycogen into glucose.

As a result, the damaged glycogen stays in the liver and other organs. Liver damage is a common result. There are five varieties or subtypes of this disease, which can vary greatly in symptoms and outcomes.

These subtypes vary based on the amount of bad glycogen in the body. There are no proven treatments for any type of glycogen storage disease, but diet can help with disease management. However, when severe liver damage occurs, a liver transplant may be the only way to prevent death.

Being the parent of a child with GSD IV can be devastating because of the poor outcomes that often accompany this diagnosis. It can also be lonely dealing with this condition as a parent or patient because the condition is so rare.

Family and friends may not understand the disease or the challenges that it brings. You may find help from online or in-person support groups for people with glycogen storage diseases.

This can help offset feelings of isolation and frustration that are common when dealing with a rare disease. These groups can often be a source of emotional support, as well as a resource for sharing disease management strategies.

GSD IV can't be prevented because it is an inherited disease. If you have a family member with this disease, genetic testing can determine your risk factors for developing this disease and passing it to your child. It's important to remember that the presence of a defective gene doesn't always mean that the disease will develop.

GSD IV can cause liver damage so severe that a liver transplant is necessary.