TaoMedAI/RareMedData huggingface dataset:
Glycogen storage disease due to glycogen debranching enzyme deficiency (ORPHA:366)
Glycogen debranching enzyme (GDE) deficiency, or glycogen storage disease type 3 (GSD 3), is a form of glycogen storage disease characterized by severe muscle weakness and hepatopathy.
Epidemiology
Estimated prevalence is approximately 1/100,000 births (it may be higher among North Africans).
Clinical description
GSD 3 commonly occurs in early childhood. Children present with hepatomegaly, growth retardation and occasional seizures related to hypoglycemia. Hepatomegaly may disappear with adulthood. Muscle weakness is slowly progressive. Other frequently associated signs include muscular hypotonia and hypertrophic cardiomyopathy. Symptoms often improve at puberty, except in the few cases where cirrhosis or myopathy appears. Biological findings include hypoglycemia without acidosis, hypertriglyceridemia, and hypertransaminasemia during childhood.
Etiology
The disease is caused by mutations in the AGL gene (1p21), leading to a deficiency in the GDE that works with the glycogen phosphorylase to catabolize glycogen. The deficiency may occur in the liver and muscle (GSD 3a) or only in the liver (GSD 3b).
Diagnostic methods
The diagnosis is based on the evidence of enzymatic deficiency in fresh leukocytes, fibroblasts, or on a liver or a muscle biopsy. Unlike GSD type 1 (see this term), there is a response to glucagon after meals.
Differential diagnosis
Differential diagnoses include the other forms of glycogen storage diseases (see these terms).
Antenatal diagnosis
Prenatal diagnosis is possible by enzyme assay and/or DNA analysis.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Treatment is based on a specific diet, with enteral nasogastric drip feeding at night in case of hypoglycemia, frequent meals, and uncooked starch supplements. For patients with myopathy, a high protein diet is also recommended.
Prognosis
Rarely, patients may develop complications such as hepatic failure or hepatocellular carcinoma.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART
Glycogen storage disease due to hepatic glycogen synthase deficiency (ORPHA:2089)
A genetically inherited anomaly of glycogen metabolism and a form of glycogen storage disease (GSD) characterized by fasting hypoglycemia. This is not a glycogenosis, strictly speaking, as the enzyme deficiency decreases glycogen reserves.
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. Patients present with morning fatigue and fasting hypoglycemia (without hepatomegaly) associated with hyperketonemia but without hyperalaninemia or hyperlactacidemia. After meals, major hyperglycemia associated with lactate and alanine increase and hyperlipidemia is observed.
Etiology
Glycogen synthetase deficiency is caused by mutations in the GYS2 gene (12p12.2).
Diagnostic methods
Biological results after glucose loading test strongly suggest the diagnosis, but formal diagnosis requires a liver biopsy showing a slightly decreased glycogen concentration and evidence of the enzyme deficiency (it is not expressed in muscles, erythrocytes, leukocytes, or fibroblasts). Molecular analysis revealing a mutation in the GYS2 gene confirms the diagnosis. Mutation analysis is an alternative to liver biopsy.
Differential diagnosis
Differential diagnoses include fructose intolerance, GSD type 1 (see these terms), and hypoglycemia.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
The condition is treated with a specific diet that includes frequent meals with high protein intake during the day and addition of uncooked starch in the evening.
Prognosis
Prognosis is favorable when the disease is correctly managed.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART
Glycogen storage disease due to lactate dehydrogenase deficiency (ORPHA:2364)
A rare genetic glycogen storage disease characterized by either lactate dehydrogenase (LDH) M- or H-subunit deficiency. Main features of LDH M-subunit deficiency are exertional fatigue and muscle pain potentially accompanied by myoglobinuria. Some patients may develop pustular psoriasis-like skin lesions. Complications of pregnancy, such as frequent abdominal pains and increased uterine tone with a risk of dystocia have also been described. LDH H-subunit deficiency manifests with low serum LDH activity of unclear clinical relevance.
Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (ORPHA:284426)
A rare glycogen storage disease characterized by easy fatigue, exertional myalgia, painful muscle stiffness, and cramps, with or without myoglobinuria. Pustular psoriasis-like eruptions with antecedent annular scaly plaques may be observed in some patients. In affected women, pregnancy may be complicated by abdominal pain and dystocia.
Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency (ORPHA:79240)
A benign inborn error of glycogen metabolism. It is the mildest form of GSD due to PhK deficiency.
Epidemiology
Prevalence is unknown.
Clinical description
The disease manifests in childhood. Patients have marked hepatomegaly and mild muscular hypotonia. Hypoglycemia may occur only after prolonged fasting. These symptoms improve with age and adults are generally asymptomatic.
Etiology
Phosphorylase kinase (PhK) is an enzyme which plays a key role in the regulation of glycogenolysis as it is required for glycogen phosphorylase activation. It consists of four copies of each four subunits (alpha, beta, gamma and calmoduline) encoded by different genes on different chromosomes and differentially expressed in various tissues. GSD due to liver and muscle PhK deficiency is due to mutations in the PHKB gene (16q12-q13) which encodes the beta subunit.
Diagnostic methods
Biochemical diagnosis can be made by measuring phosphorylase kinase activity in blood cells or in a liver or muscle biopsy. Serum transaminase levels may also be elevated. Genetic testing is useful to confirm or establish the diagnosis.
Differential diagnosis
Differential diagnoses include other glycogen storage diseases such as GSD due to liver phosphorylase deficiency (GSD type VI), GSD due to glycogen debranching enzyme deficiency (GSD type III), and GSD due to glucose-6-phosphatase (GSD type I) (see these terms).
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Most patients do not require any specific treatment; a few patients may need to use cornstarch snacks.
Prognosis
Prognosis is good.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART  - Pr Philippe LABRUNE
Glycogen storage disease due to liver glycogen phosphorylase deficiency (ORPHA:369)
Liver phosphorylase deficiency, or glycogen storage disease type 6b (Hers' disease, GSD 6b) is a benign and rare form of glycogen storage disease.
Clinical description
The disease usually occurs in childhood and is characterized by hepatomegaly and growth delay. Hypoglycemic episodes are mild or absent, and hypertransaminasemia and hyperlipidemia are moderate and unconstant. Hepatomegaly usually improves with age and disappears entirely at puberty.
Etiology
Transmission is autosomal recessive and mutations in the PYGL gene (14q21-q22) have been identified in patients.
Diagnostic methods
Diagnosis is based on biochemical findings revealing excess glycogen and partial deficiency of total and active phosphorylase in liver biopsy.
Management and treatment
A diet with high carbohydrate intake and regular meals prevents hypoglycemia in children, but most patients require no specific treatment.
Prognosis
Prognosis is usually good.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART
Glycogen storage disease due to muscle and heart glycogen synthase deficiency (ORPHA:137625)
Glycogen storage disease due to muscle and heart glycogen synthase deficiency is characterised by muscle and heart glycogen deficiency. It has been described in three siblings (two brothers and their younger sister). The older brother died at 10.5 years of age as a result of sudden cardiac arrest and the younger brother presented with hypertrophic cardiomyopathy, abnormal heart rate and blood pressure during exercise, and muscle fatigability. The sister showed no symptoms but a lack of glycogen was identified through muscle biopsy. The syndrome is caused by homozygous missense mutations in the gene encoding muscle glycogen synthase.
Glycogen storage disease due to muscle beta-enolase deficiency (ORPHA:99849)
A rare glycolysis disorder characterized clinically by exercise intolerance and myalgia due to severe enolase deficiency in muscle.
Glycogen storage disease due to muscle glycogen phosphorylase deficiency (ORPHA:368)
Myophosphorylase deficiency (McArdle's disease), or glycogen storage disease type 5 (GSD5) , is a severe form of glycogen storage disease characterized by exercise intolerance.
Epidemiology
Prevalence is unknown.
Clinical description
Onset occurs in childhood. Patients present with a syndrome of muscular exercise intolerance with myalgia, cramps, fatigue, and muscle weakness. Massive elevation of creatine-kinase and rhabdomyolysis with myoglobinuria (dark urine) after exercise is noted in around 50% of patients, potentially leading to acute kidney failure. A 'second wind' phenomenon with relief of myalgia and fatigue after a few minutes of rest is observed in many patients. The clinical presentation is usually very classical, but some patients may have very moderate forms. In a few cases, onset very early in life with hypotonia, generalized muscle weakness and progressive respiratory failure has been described.
Etiology
The condition is caused by mutations in the PYGM gene (11q13), leading to muscle phosphorylase deficiency. Mutation p.R50X may account for 40% to 50% of the alleles in Caucasian populations.
Diagnostic methods
The diagnosis is based on biological findings revealing a lack of lactate elevation in blood during ischemic forearm test, excess glycogen, and deficient phosphorylase activity in the muscle biopsy.
Differential diagnosis
The differential diagnosis should include GSD type 7 (see this term).
Genetic counseling
The condition is autosomal recessive.
Management and treatment
Treatment is based on controlled physical training in order to develop mitochondrial oxidation capacities in muscles, and programmed glucose intake according to exercising periods. Diets with high protein intake have yielded variable results.
Prognosis
Prognosis is favorable when severe rhabdomyolysis is avoided. However, myoglobinuria may lead to potentially life-threatening renal failure.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART
Glycogen storage disease due to muscle phosphofructokinase deficiency (ORPHA:371)
Muscle phosphofructokinase (PFK) deficiency (Tarui's disease), or glycogen storage disease type 7 (GSD7), is a rare form of glycogen storage disease characterized by exertional fatigue and muscular exercise intolerance. It occurs in childhood.
Epidemiology
About 100 cases have been reported worldwide.
Clinical description
Clinical signs are muscular exercise intolerance (more severe than in type 5; see this term). Compensated hemolysis (increased bilirubin and reticulocytes) and hyperuricemia are associated. A rapidly fatal infant form has also been observed in 6 families.
Etiology
The condition is caused by mutations in the PFKM gene (12q13) encoding the muscular isoenzyme of PFK, a key enzyme in the regulation of anaerobic glycolysis which has 3 isoenzymes (for the muscle, liver, and platelets).
Diagnostic methods
The diagnosis is based on biological findings, revealing increased amounts of abnormal glycogen and enzyme deficiency (1 to 33% residual activity) in a muscle biopsy, whereas activity in erythrocytes is over 50%.
Differential diagnosis
Differential diagnoses include the other forms of glycogen storage disease (see these terms).
Genetic counseling
The condition is autosomal recessive, although a few cases with pseudodominance or symptomatic heterozygous individuals have been found.
Management and treatment
The only treatment is to avoid intensive exercise. It should be noted that carbohydrates induce lower muscular performance (due to the decreased amounts of free fatty acids and ketone bodies).
Prognosis
Myoglobinuria may lead to renal failure.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART
Glycogen storage disease due to muscle phosphorylase kinase deficiency (ORPHA:715)
Glycogen storage disease due to muscle phosphorylase kinase (PhK) deficiency is a benign inborn error of glycogen metabolism characterized by exercise intolerance.
Epidemiology
The disease is very rare with less than 30 patients reported in the literature.
Clinical description
The disease starts generally in adolescence or adulthood. Patients may present with exercise intolerance with myalgia, cramps, fatigue, and sometimes myoglobinuria. In some cases, patients may present with progressive muscle weakness. Symptoms are usually mild, and myopathy may be asymptomatic. A neonatal form with generalized muscular hypotonia and respiratory insufficiency has also been described.
Etiology
Phosphorylase kinase (PhK) is an enzyme which plays a key role in the regulation of glycogenolysis as it is required for glycogen phosphorylase activation. It consists of four copies of each four subunits (alpha, beta, gamma and calmoduline) encoded by different genes on different chromosomes and differentially expressed in various tissues. Muscle-specific isoforms of the alpha and gamma subunits are encoded by the PHKA1 gene and the PHKG1 gene respectively, but until now mutations have been only identified in the PHKA1 gene and the transmission is X-linked.
Diagnostic methods
Biochemical diagnosis of the muscle form can be made by measuring phosphorylase kinase activity in a muscle biopsy. Genetic testing is useful to confirm or establish the diagnosis.
Differential diagnosis
Differential diagnoses include GSD due to myophosphorylase deficiency (GSD type V), and other GSDs affecting the muscle (GSD types XI, XII, XIII and XIV) (see these terms).
Management and treatment
Most patients do not require any specific treatment.
Prognosis
Prognosis is generally good.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART  - Pr Philippe LABRUNE  - Pr Pascal LAFORET
Glycogen storage disease due to phosphoglycerate kinase 1 deficiency (ORPHA:713)
A rare inborn errors of metabolism characterized by variable combinations of non-spherocytic hemolytic anemia, myopathy, and various central nervous system abnormalities.
Epidemiology
Phosphoglycerate kinase (PGK) deficiency prevalence is unknown but about 30 unrelated affected families have been reported so far.
Clinical description
The majority of patients present with chronic hemolytic anemia, which may be severe in some cases. Myopathy is a common finding and is characterized by exercise-intolerance, muscle weakness, cramping, myalgia and episodes of myoglobinuria. Rhabdomyolysis has also been reported in a few patients. Intellectual deficit is frequent, and other central nervous system manifestations may be also present including hemiplegic migraines, epilepsy, ataxia and tremor. Only a few patients show all three cardinal features of the disorder (hemolytic anemia, central nervous system abnormalities and myopathy), and several cases of PGK deficiency with myopathy in the absence of hemolytic anemia have been reported. Only one asymptomatic patient has been described with mild PGK deficiency.
Etiology
PGK deficiency is caused by mutations in the PGK1 gene (Xq13.3) and around 20 different disease-causing variants have been identified so far in affected families. PGK is a key enzyme in the glycolytic pathway catalyzing the conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate and generating ATP. PGK is a ubiquitous enzyme expressed in all tissues except the testes.
Diagnostic methods
Diagnosis is made on the basis of the clinical picture, together with biochemical studies revealing low erythrocyte and muscle PGK enzyme activity (below 23% and 25% of normal respectively), and identification of PGK1 gene mutations by molecular analysis.
Differential diagnosis
The differential diagnosis should include other causes of hereditary non-spherocytic hemolytic anemia.
Antenatal diagnosis
Molecular prenatal diagnosis is feasible for families of an index case.
Genetic counseling
PGK deficiency is inherited as an X-linked trait and most of the reported patients were hemizygous males. However, heterozygous females may have a variable degree of hemolytic anemia. All women born to affected men will be carriers (mild manifesting or not) with no male to male transmission. Female carriers have a 50 % risk of an affected male or female carrier with each pregnancy.
Management and treatment
In patients with severe chronic anemia, regular blood transfusions are required. Splenectomy has been shown to be beneficial in some cases.
Prognosis
The prognosis is variable, depending on the severity of the anemia and on the presence of the other manifestations.

                            Last update: 
                            November 2019


                            - Expert reviewer(s): 
                            Pr Mark TARNOPOLSKY
Glycogen storage disease due to phosphorylase kinase deficiency (ORPHA:370)
Glycogen storage disease (GSD) due to phosphorylase kinase deficiency is a group of inborn errors of glycogen metabolism that is clinically and genetically heterogeneous. This group comprises GSD due to liver phosphorylase kinase (PhK) deficiency, GSD due to muscle PhK deficiency and GSD due to liver and muscle PhK deficiency (see these terms).
Epidemiology
The prevalence at birth is estimated at around 1/100,000.
Clinical description
GSD due to liver PhK deficiency is the most common sub-type and presents in early childhood with hepatomegaly, growth retardation, and mild delay in motor development. During adulthood, symptoms usually disappear. Patients with GSD due to liver and muscle PhK deficiency may have marked hepatomegaly and mild muscular hypotonia in childhood. GSD due to muscle PhK deficiency presents in adolescence or adulthood with exercise intolerance, myalgia, and sometimes myoglobinuria but symptoms are generally mild.
Etiology
Phosphorylase kinase (PhK) is an enzyme which plays a key role in the regulation of glycogenolysis as it is required for glycogen phosphorylase activation. It consists of four copies of each four subunits (alpha, beta, gamma and calmoduline) encoded by different genes on different chromosomes and differentially expressed in various tissues. GSD due to liver PhK deficiency is due to mutations in the PHKA2 or PHKG2 genes encoding the liver isoforms of the alpha and gamma subunits of PhK. Transmission is X-linked and autosomal recessive, respectively. GSD due to liver and muscle PhK deficiency is transmitted in an autosomal recessive manner and is due to mutations in the PHKB gene which encodes the beta subunit of PhK. The muscle-specific isoforms of the alpha and gamma subunits of PhK are encoded by the PHKA1 and PHKG1 genes respectively, but until now mutations have only been found in the PHKA1 gene in patients with GSD due to muscle PhK deficiency. Transmission is X-linked.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART  - Pr Philippe LABRUNE  - Pr Pascal LAFORET
Glycogen storage disease with severe cardiomyopathy due to glycogenin deficiency (ORPHA:263297)
A rare autosomal recessive glycogen storage disease characterized by severe cardiomyopathy and cardiac dilatation potentially progressing to heart failure requiring transplantation. Cardiomyocytes show large inclusions of storage material consistent with polyglucosan. Clinical evidence of skeletal muscle involvement is usually absent.
GM1 gangliosidosis type 1 (ORPHA:79255)
GM1 gangliosidosis type 1 is the severe infantile form of GM1 gangliosidosis (see this term) with variable neurological and systemic manifestations.
Epidemiology
Type 1 is the most frequent form of GM1 gangliosidosis but the exact prevalence is not known. About 200 cases have been reported to date. Overall prevalence at birth of GM1 gangliosidosis is estimated to be approximately 1:100,000 to 200,000 live births.
Clinical description
The onset of this disorder may be in utero (non immune hydrops fetalis) or by the age of six months. Clinical signs are variable and include arrest/regression of neurological development, hypotonia, visceromegaly, macular cherry-red spots, dysostosis and coarse facial features. Cardiomyopathy may occur.
Etiology
GM1 gangliosidosis is caused by mutations in the GLB1 gene (3p22.3) coding for beta-galactosidase.
Diagnostic methods
Diagnosis is based on clinical signs although classic signs are not always present at diagnosis. Biochemical and/or molecular genetic tests confirm the diagnosis.
Differential diagnosis
Differential diagnosis includes mucopolysaccharidoses, sphingolipidoses and oligosaccharidoses (see these terms).
Antenatal diagnosis
Prenatal diagnosis can be performed by analysis of beta-galactosidase activity and/or by GLB1 molecular analysis in either chorionic villus (CV) cells or amniotic fluid cells if mutations are found in an index case.
Genetic counseling
GM1 gangliosidosis is an autosomal recessive disease. Genetic counseling should be provided to affected families.
Management and treatment
Treatment for patients with GM1 gangliosidosis is symptomatic and supportive.
Prognosis
Prognosis is very poor with life-expectancy rarely exceeding 2 years. Causes of death include pneumonia due to recurrent aspiration and cardiopulmonary failure.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Dr Anna CACIOTTI  - Dr Maria Alice DONATI  - Dr Amelia MORRONE