The clinical presentation of this autosomal recessive genetic disease exhibits significant variations, having in mind the fact that both hyperglycemia and hypoglycemia can occur [1] [2]. Due to frequent feeding during infancy, patients are usually asymptomatic during this period of life, but as nighttime feeding gradually ceases, symptoms most commonly appear before breakfast, when insufficient glycogen stores and consequent hypoglycemia manifest as lethargy, nausea, vomiting, pallor and seizures in some cases [1] [3]. Even in the absence of overnight feeds, infants and children rarely suffer from severe fasting ketotic hypoglycemia because fatty acid oxidation is able to provide enough energy for the central nervous system and the brain until the mealtime, and many children are even asymptomatic for a prolonged period of time [4]. Long-term complications, such as growth impairment, osteopenia, hyperlipidemia and developmental delay, which are more prevalent among other GSDs, are rarely seen in GSD type 0 and the majority of children have a preserved cognitive function [3] [4]. On the other hand, postprandial hyperglycemia is not an uncommon finding in these patients, the reason being the inability of the liver to synthesize glycogen from glucose after meals, as hepatic synthase is the key enzyme in this process [2]. This finding may paradoxically point to diabetes mellitus as the underlying cause [3]. Although often accompanied by hyperlipidemia and hyperlactatemia, symptoms are rarely present and the diagnosis is often made incidentally in either case [2] [4].

• Splenomegaly

  Hepatomegaly is seen in all except: Type 0 (Glycogen synthase deficiency) Type IV or Anderson’s disease (Hepatomegaly may be absent and death is early, i.e. in 2 years due to early cirrhosis) Hepatomegaly with splenomegaly and other generalized signs [epomedicine.com]

  Symptoms due to complications of liver cirrhosis: portal hypertension, esophageal varices, encephalopathy, splenomegaly, ascites, reduced renal function Rarely, associated with hepatocellular carcinoma. [quizlet.com]

  Clinical features : Hepatomegaly, failure to thrive, cirrhosis, splenomegaly, jaundice, hypotonia, waddling gait, lumbar lordosis. [patient.info]

  Splenomegaly, liver cirrhosis, doll facies, osteoporosis, neurologic disease, elevated serum lactate, metabolic acidosis and renal tubular acidosis have been described very rarely. [wjgnet.com]

• Anemia

  […] hypoglycemia in children with a focus on the causes of ketotic hypoglycemia Investigation into the cause of morbidity type 0 and I glycogen storage disease including the pathophysiology of hepatic adenomas, hepatocellular carcinoma, nephrolithiasis, anemia [connecticutchildrens.org]

  PMID 27490698. ^ "Aplastic Anemia". The Lecturio Medical Concept Library. Retrieved 1 August 2021. ^ Evans RS, Takahashi K, Duane RT, Payne R, Liu C (1951). [en.wikipedia.org]

  (fasting hypoglycemia), liver enzymes AST/ALT (hepatomegaly), plasma lactate (elevated, lactic acidosis), plasma bicarbonate (decreased due to acidosis), uric acid (increased due to acidosis), plasma lipids (increased cholesterol and triglycerides), anemia [quizlet.com]

  P74 ) Endocrine, nutritional and metabolic diseases E70-E88 2019 ICD-10-CM Range E70-E88 Metabolic disorders Type 1 Excludes androgen insensitivity syndrome ( E34.5- ) congenital adrenal hyperplasia ( E25.0 ) Ehlers-Danlos syndrome ( Q79.6 ) hemolytic anemias [icd10data.com]

  If there is anemia, the causes must be evaluated and appropriate treatment should be started (for a comprehensive dietary therapy of GSD-I, see reference No 18). [wjgnet.com]

• Poor Growth

  I had poor growth, low blood sugar levels, a greatly enlarged liver, abnormal blood tests and what they described as a “porcelain doll” look. My doctors called specialists in Florida to seek help on a diagnosis. [themighty.com]

  Clinical features : Seizures in infancy, hypoglycaemia, poor growth, hepatomegaly, moderate progressive myopathy. Symptoms can regress with age. [patient.info]

  With ageing, the patient may present with poor growth, short stature, and rachitic changes[ 2 ]. Rarely, xanthoma may be found on extensor surfaces, such as the elbows and knees. [wjgnet.com]

• Recurrent Infection

  Whilst patients with GSD Ib may have neutropenia and neutrophil dysfunction, intervention is not always required unless there are poor wound healing or recurrent infections. Often, infections are worse with poor metabolic control. [tp.amegroups.com]

  In addition to clinical symptoms and findings seen in GSD-Ia, recurrent infections, neutropenia, and neutrophil dysfunction are recognized as distinctive features of GSD-Ib. [wjgnet.com]

• Failure to Thrive

  […] to thrive Faltering weight Weight faltering [ more ] 0001508 Global developmental delay 0001263 Hyperlipidemia Elevated lipids in blood 0003077 Lethargy 0001254 Seizures Seizure 0001250 Short stature Decreased body height Small stature [ more ] 0004322 [rarediseases.info.nih.gov]

  Symptoms: Presents in infancy to early childhood; hypoglycemia and severe liver disease with hepatomegaly and failure to thrive. Liver failure and cirrhosis by age 5. [quizlet.com]

  Clinical features : Hepatomegaly, failure to thrive, cirrhosis, splenomegaly, jaundice, hypotonia, waddling gait, lumbar lordosis. [patient.info]

  Failure to thrive, enlarged liver, liver dysfunction, progressive liver cirrhosis with portal hypertension, death often from liver failure Non-progressive hepatic subtype. [slideplayer.com]

  Within the first months of life, affected infants have difficulty gaining weight and growing at the expected rate (failure to thrive) and develop an enlarged liver (hepatomegaly). [icdlist.com]

• Hepatomegaly

  The diagnosis of GSD0 should be considered in a child with ketotic fasting hypoglycemia with postprandial hyperglycemia but without hepatomegaly. [ncbi.nlm.nih.gov]

  Diet and other therapies are only partially successful at limiting hepatomegaly, hypoglycemia. [quizlet.com]

  Hepatomegaly is seen in all except: Type 0 (Glycogen synthase deficiency) Type IV or Anderson’s disease (Hepatomegaly may be absent and death is early, i.e. in 2 years due to early cirrhosis) Hepatomegaly with splenomegaly and other generalized signs [epomedicine.com]

  A glycogen build up is found in liver causing hepatomegaly. [edusanjalbiochemist.blogspot.com]

  Clinical symptoms in IXa include hepatomegaly, growth restriction, hyperlipidaemia and fasting ketosis. [patient.info]

• Liver Dysfunction

  AST>ALT), serum creatinine kinase (branching enzyme defect also effects muscle), enzyme analysis in fibroblasts, imaging (to look for hepatomegaly), liver biopsy (to see liver dysfunction), ischemic forearm test (low lactate production with exercise [quizlet.com]

  Failure to thrive, enlarged liver, liver dysfunction, progressive liver cirrhosis with portal hypertension, death often from liver failure Non-progressive hepatic subtype. [slideplayer.com]

  Typically a liver biopsy is performed for this non-specific hepatomegaly and the characteristic pathological finding of glycogen laden hepatocytes leads to the diagnosis. Mild liver dysfunction may be seen. [tp.amegroups.com]

  In a small group of the patients there are only muscle symptoms as adults without any sign or history of liver dysfunction after childhood[ 94, 95 ]. Liver symptoms improve with age and usually disappear after puberty. [wjgnet.com]

• Xanthoma

  Rarely, xanthoma may be found on extensor surfaces, such as the elbows and knees. [wjgnet.com]

• Muscle Cramp

  Myopathic forms: Type V and VII Glycogen deposition in muscle Muscle cramp after exercise Exercise induced lactic acidosis (block in glycolysis) There may be myoglobinemia 3. [epomedicine.com]

  Secondary symptoms Quick to tire, muscle cramps Treatment Regular snacks, cornstarch to reduce overnight hypoglycemia. [agsd.org.uk]

  Furthermore a person with GSD 0 may have muscle cramps because the body is trying to make energy from accumulated lactic acid. A person with Type 0 Glycogen Storage Disease will typically look no different from a person who does not have GSD 0. [agsdus.org]

  […] that are characterized by weakness, muscle cramps, and sometimes myoglobinuria. [britannica.com]

  In the muscle, glycogen is the source of energy for muscle activity. Thus, glycogen storage disorders can manifest as hypoglycemia, ketosis, lethargy, fatigue, weakness, muscle cramping, and exercise intolerance. [emedicine.com]

• Lordosis

  Clinical features : Hepatomegaly, failure to thrive, cirrhosis, splenomegaly, jaundice, hypotonia, waddling gait, lumbar lordosis. [patient.info]

• Lethargy

  […] feeding during infancy, patients are usually asymptomatic during this period of life, but as nighttime feeding gradually ceases, symptoms most commonly appear before breakfast, when insufficient glycogen stores and consequent hypoglycemia manifest as lethargy [symptoma.com]

  Thus, glycogen storage disorders can manifest as hypoglycemia, ketosis, lethargy, fatigue, weakness, muscle cramping, and exercise intolerance. There are two isoforms of the glycogen synthase enzyme. [emedicine.com]

  Abnormality of the gastrointestinal tract 0011024 Elevated hepatic transaminase High liver enzymes 0002910 Failure to thrive Faltering weight Weight faltering [ more ] 0001508 Global developmental delay 0001263 Hyperlipidemia Elevated lipids in blood 0003077 Lethargy [rarediseases.info.nih.gov]

  Signs of hypoglycemia become apparent when affected infants begin sleeping through the night and stop late-night feedings; these infants exhibit extreme tiredness (lethargy), pale skin (pallor), and nausea. [medlineplus.gov]

• Convulsions

  Before breakfast children may have drowsiness, look pale, have vomiting, fatigue and sometimes convulsions. If a GP investigates a child lacking energy, hypoglycemia is often discovered through morning urine samples. Latest news! [agsd.org.uk]

  Children may have early-morning (before eating breakfast) drowsiness, appearance of looking pale, vomiting and fatigue, and sometimes convulsions associated with low blood glucose. [agsdus.org]

  8 GSD Type 1 Edgar von Gierke’s Disease Most common disease type (approximately 1 in 20,000 infants) Characterized by: -an abnormally large abdomen due to an accumulation of glycogen in the liver -prominent hypoglycemia in between meals (may cause convulsions [slideplayer.com]

  In the early morning the child may have low blood sugar which could cause: Paleness Vomiting Extreme fatigue Convulsions The children may also have a mild growth delay. They also may have poor exercise tolerance. [wmhs.com]

  Gitzelmann et al. (1996) stated that the disorder should be sought in children who, before the first meal of the day, present with drowsiness, lack of attention, pallor, uncoordinated eye movements, disorientation, or convulsions, and who have hypoglycemia [sandwalk.blogspot.com]

• Irritability

  Showing of 18 | 30%-79% of people have these symptoms Glycosuria Glucose in urine 0003076 Irritability Irritable 0000737 Ketonuria 0002919 Ketosis High levels of ketone bodies 0001946 Ketotic hypoglycemia 0012734 Postprandial hyperglycemia 0011998 5%- [rarediseases.info.nih.gov]

  Common symptoms include: Muscle weakness Growth delay during childhood Swollen abdomen due to an enlarged liver Signs of low blood sugar including Paleness Irritability Fatigue Type 4: Type 4 appears during infancy. [wmhs.com]

  Type 0 Early age at presentation Fasting low blood sugar (irritability, crying until fed, waking up in the night and demanding food) Increased lactate levels in the blood Fasting ketone bodies in the blood Type I Low blood sugar with few hours of fasting [childrenliverindia.org]

  These symptoms may exist because individuals with neutropenia often have infection.[3] Children may show signs of irritability and poor feeding.[10] Additionally, hypotension has also been observed in individuals who have this condition.[6] Causes[edit [en.wikipedia.org]

  Main symptoms are tremors, irritability, hyperventilation, cyanosis, apnea, convulsions, paleness, sweating, cerebral edema/dysfunction, coma and death, particularly in the morning or before feedings. [wjgnet.com]

Children suffering from glycogen storage disease type 0 are most frequently identified when laboratory testing reveals hypoglycemia during evaluation for illnesses, for eg. gastrointestinal or other conditions that impair proper food intake [4]. Nevertheless, a thorough patient history is a mandatory step during workup, and valuable information can be obtained regarding any changes in eating habits and the appearance of symptoms as a result of these changes. A thorough physical examination should follow, but a presumptive diagnosis is made by determining levels of glucose and ketones in blood and urine, while measurement of lactate levels is also a good initial method [4]. Administration of either glucose or galactose and subsequent measurements of blood lactate and lipids, as well as glucose, is a highly useful procedure to confirm aberrations in the glycolytic pathway [1]. Additional laboratory parameters that support GSD type 0 are elevated liver enzymes (alanine and aspartate aminotransferase, or ALT and AST, respectively) [4]. If valid clinical suspicion existed toward GSD type 0 in previous years, liver biopsy was considered to the gold standard in the diagnostic workup, but the introduction of non-invasive genetic tests to detect specific mutations have changed the role of biopsy when it comes to GSD type 0 [1] [4]. Identification of glycogen synthase 2 (GYS2) gene mutations on chromosome 12p12.2 is diagnostic for this GSD [1] [3].

• Glycosuria

  Showing of 18 | 30%-79% of people have these symptoms Glycosuria Glucose in urine 0003076 Irritability Irritable 0000737 Ketonuria 0002919 Ketosis High levels of ketone bodies 0001946 Ketotic hypoglycemia 0012734 Postprandial hyperglycemia 0011998 5%- [rarediseases.info.nih.gov]

  Glycosuria and ketonuria occur after breakfast and therefore may be confused with diabetes mellitus. Treatment : adequate diet and avoidance of fasting hypoglycaemia. [patient.info]

  However, the glucose transport defect is very complex with generalised tubulopathy leading to glycosuria. Renal tubular dysfunction leads to mineral wasting and consequent rickets ( 29 ). [tp.amegroups.com]

• Enlargement of the Liver

  The symptoms of disease in the liver group are similar, ranging from symptomatic hypoglycemia and ketoacidosis to largely asymptomatic enlargement of the liver (hepatomegaly). [britannica.com]

  Some GSDs affect mostly the liver. These include Types 0, I, III, VI, and IX. These types (except for GSD type 0) may cause the liver to become enlarged. [my.clevelandclinic.org]

  On physical examination the liver may be enlarged at birth or it becomes enlarged in a very short time[ 2 ]. There is abdominal protuberance because of massive hepatomegaly. [wjgnet.com]

• Fasting Hypoglycemia

  The diagnosis of GSD0 should be considered in a child with ketotic fasting hypoglycemia with postprandial hyperglycemia but without hepatomegaly. [ncbi.nlm.nih.gov]

  Mortality/Morbidity The major morbidity is a risk of fasting hypoglycemia, which can vary in severity and frequency. [emedicine.com]

  Patients present with morning fatigue and fasting hypoglycemia (without hepatomegaly) associated with hyperketonemia but without hyperalaninemia or hyperlactacidemia. [orpha.net]

  […] and suspected glycogen-storage disease type 0 (GSD-0) include (1) the presence or absence of hepatomegaly; (2) the characteristic schedule of hypoglycemia, including unpredictable, postprandial, short fast, long fast, or precipitating factors; (3) the [en.wikipedia.org]

• Hyperlactacidemia

  Patients present with morning fatigue and fasting hypoglycemia (without hepatomegaly) associated with hyperketonemia but without hyperalaninemia or hyperlactacidemia. [orpha.net]

• Hepatocellular Carcinoma

  carcinoma, nephrolithiasis, anemia, and focal segmental glomerulosclerosis Investigation of new medical treatments for glycogen storage disease [connecticutchildrens.org]

  Complications : include hepatocellular carcinoma, liver failure, heart failure, nerve dysfunction and ventricular arrhythmia. Prognosis : mostly death by age 4, due to cirrhosis and portal hypertension. [patient.info]

  Symptoms due to complications of liver cirrhosis: portal hypertension, esophageal varices, encephalopathy, splenomegaly, ascites, reduced renal function Rarely, associated with hepatocellular carcinoma. [quizlet.com]

  In two of these patients (one GSDIIIb) hepatocellular carcinoma (HCC) was diagnosed postoperatively upon pathological examination. [link.springer.com]

  Carcinoma (liver cancer) Liver cirrhosis ----Type IV, maybe III and IX Renal disease ---hypertension, stones, renal dysfunction Recurrent infections – Type I b Liver, kidney, heart failure What is the life expectancy of a person with glycogen storage [childrenliverindia.org]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

If you have questions about which treatment is right for you, talk to your healthcare professional. [rarediseases.info.nih.gov]

Myozyme treatment clearly prolongs ventilator-free survival and overall survival. Early diagnosis and early treatment leads to much better outcomes. [en.wikipedia.org]

However, the focus of the book remains clinical, describing symptoms and signs at presentation, how to come to a diagnosis and methods for treatment. As with the previous edition, the book can be used in two main ways. [books.google.com]

Prognosis Prognosis is favorable when the disease is correctly managed. The documents contained in this web site are presented for information purposes only. [orpha.net]

Prognosis : mostly death by age 4, due to cirrhosis and portal hypertension. Type V: McArdle's disease See the separate article on McArdle's Glycogen Storage Disease. [patient.info]

Prognosis depends on the age of onset on symptoms with a better prognosis being associated with later onset disease. It has an autosomal recessive inheritance pattern. [en.wikipedia.org]

The prognosis is usually favorable when the disease is correctly managed. [1] This condition differs from another form of GSD 0 which chiefly affects the muscles and heart ( Glycogen storage disease type 0, muscle ) and is thought to be caused by mutations [rarediseases.info.nih.gov]

Etiology Glycogen synthetase deficiency is caused by mutations in the GYS2 gene (12p12.2). [orpha.net]

Etiology germline mutation in the glycogen synthase 2 Physiopathology Glucose use is strictly controlled and abnormal glucose handling is associated with some human diseases, such as glycogen storage diseases and diabetes. [humpath.com]

"Primary thrombocytopenic purpura and acquired hemolytic anemia; evidence for a common etiology". Archives of Internal Medicine. 87 (1): 48–65. doi:10.1001/archinte.1951.03810010058005. PMID 14782741. ^ "Evans syndrome". [en.wikipedia.org]

Type 1 Diabetes Type 2 Diabetes Etiology Autoimmune Peripheral insulin resistance Formerly known as IDDM NIDDM or “adult onset” diabetes Age of onset Younger Older Obesity Rare Common Family History Rare Common HLA association/Genetic association Yes [news-medical.net]

Summary Epidemiology It is an extremely rare disease; about 20 cases have been reported in the literature so far. Clinical description It commonly appears in infancy or in early childhood. [orpha.net]

The 4th edition includes an entirely new section on pediatric obesity: epidemiology, pathophysiology, assessment and treatment. It includes new chapters on celiac disease, food allergies and iron. [books.google.com]

Epidemiology Frequency International The overall frequency of glycogen-storage disease is approximately 1 case per 20,000-25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. [emedicine.com]

Epidemiology [ edit ] The overall frequency of glycogen-storage disease is approximately 1 case per 20,000–25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. [en.wikipedia.org]

Among the pediatric texts available, none deals with the physiologic or pathophysiologic basis of nutrition in pediatric health and disease in children of all ages. [books.google.com]

"Diabetes Pathophysiology". News-Medical. https://www.news-medical.net/health/Diabetes-Pathophysiology.aspx. (accessed November 03, 2022). Harvard Mandal, Ananya. 2019. Diabetes Pathophysiology. [news-medical.net]

[…] glycogen storage disease including the pathophysiology of hepatic adenomas, hepatocellular carcinoma, nephrolithiasis, anemia, and focal segmental glomerulosclerosis Investigation of new medical treatments for glycogen storage disease [connecticutchildrens.org]

Adrogue, Metabolic acidosis: pathophysiology, diagnosis and management. J Nephrol. 19 Suppl. 9, S62 (2006) M. Kosch et al., Störungen des Säure-Basen-HaushaltsRationale Diagnostik und ökonomische Therapie. Dtsch. Ärzteblatt 102, B 1603 (2005) Y.S. [charite.de]

Pathophysiology In the early stages of fasting, the liver provides a steady source of glucose from glycogen breakdown (or glycogenolysis). [emedicine.com]

The goal of treatment for Type 0 Glycogen Storage Disease is to prevent low blood sugar (hypoglycemia) by avoiding fasting. Frequent meals and snacks can be given every 3-4 hours during the day. [agsdus.org]

The Lipid Research Clinics Coronary Primary Prevention Trial Results, II: the relationship of reduction in incidence of coronary heart disease to cholesterol lowering. ‎ [books.google.es]

For some children, eating several small meals rich in sugars and starches every day helps prevent blood sugar levels from dropping. Cornstarch. [childrenliverindia.org]

McGill University Health Center Brief Summary: The aim of the present study is to determine if there is a change in quality and quantity of sleep perceived by adults and children with GSD and their parents while starting a modified UCCS (Glycosade) to prevent [clinicaltrials.gov]

Prevention There is no way to prevent GSDs. However, early treatment can help control the disease once a person has it. If you have a GSD or a family history of the disorder, you may want to consult a genetic counselor. [wmhs.com]

1. Özen H. Glycogen storage diseases: New perspectives. World J Gastroenterol. 2007;13(18):2541-2553.
2. Soggia AP, Correa-Giannella ML, Fortes MAH, Luna AMC, Pereira MAA. A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0. BMC Medical Genetics. 2010;11:3.
3. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
4. Weinstein DA, Correia CE, Saunders AC, Wolfsdorf JI. Hepatic Glycogen Synthase Deficiency: An Infrequently Recognized Cause of Ketotic Hypoglycemia. Mol Genet Metab. 2006;87(4):284-288.