User:Tony Mach/inborn
By affected system
[edit]Digestion
[edit]Lactose intolerance.
Fructose malabsorption.
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Overview of intracellular carbohydrate metabolism
[edit]| Metabolism of common monosaccharides, including glycolysis, gluconeogenesis, glycogenesis and glycogenolysis |
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Glycogenesis
[edit]Glycogenesis is the metabolic pathway in which glycogen is created. Glycogen, which consists of branched long chains made out of the simple sugar glucose, is an energy storage for carbohydrates in many human cells; this is most important in liver, muscle and certain brain cells.
The monosaccharide glucose-6-phosphate (G-6-P) is typically the input substance for glycogenesis. G-6-P is most commonly created from glucose by the action of the enzymes glucokinase (see glycolysis step 1) or hexokinase.
On an alternative metabolic pathway the simple sugar galactose (Gal, which is typically derived from lactose) is converted by the enzyme galactokinase (GALK) to galactose-1-phosphate (Gal-1-P), which in turn is converted by the enzyme galactose-1-phosphate uridylyltransferase (GALT) to glucose-1-phosphate (G-1-P), which can also serve as an substrate for glycogen synthesis – this bypasses the first step of glycogenesis (the enzyme phosphoglucomutase PGM).
The enzyme glycogenin (GYG) is needed to create initial short glycogen chains, which are lengthened and branched by the other enzymes of glycogenesis.
Current version at: Inborn errors of carbohydrate metabolism#Glycogenesis
| Glycogenic step Enzyme |
Gene: Organ(s) Disease (Synonyms) |
Reported symptoms. Forms (if applicable) Note: Not all patients have all symptoms; severity and presentation can vary. |
Diagnostic tests | Treatment | References and links |
|---|---|---|---|---|---|
| Glycogenesis Step 1 Phosphoglucomutase 1 (Also last step of glycogenolysis) |
PGM1: Liver, muscle, other CDG syndrome type It (CDG1T, PGM1-CDG, phosphoglucomutase 1 deficiency, PGM1 deficiency) formerly: GSD type XIV (GSD 14) |
Wide range of manifestations and severity. Commonly cleft lip and bifid uvula, hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance. | NLM/GHR:PGM1 OMIM:PGM1 OMIM:CDG1T ORPHA:CDG1T | ||
| Glycogenesis Step 2 UDP-glucose pyrophosphorylase |
UGP2 No known inborn disease |
- | - | - | OMIM:UGP2 |
| Glycogenesis Step 3 Glycogen synthase |
GYS1: Muscle GYS2: Liver GSD type 0 (GSD 0, glycogen synthetase deficiency) |
GSD0A (liver): Infancy or in early childhood onset. Morning fatigue and fasting hypoglycemia, hyperketonemia. Without hepatomegaly, hyperalaninemia or hyperlactacidemia. After meals, major hyperglycemia associated with lactate and alanine increase and hyperlipidemia. GSD0B (muscle): Myopathy, cardiomyopathy, exercise intolerance. |
NLM/GHR:GYS1 OMIM:GYS1 NLM/GHR:GYS2 OMIM:GYS2 NLM/GHR:GSD0 OMIM:GSD0A ORPHA:GSD0A OMIM:GSD0B ORPHA:GSD0B | ||
| Glycogenesis step 4 Glycogen branching enzyme |
GBE1: Liver, muscle GSD type IV (GSD 4, Andersen's disease, amylopectinosis, brancher deficiency, glycogen branching enzyme deficiency, familial cirrhosis with deposition of abnormal glycogen) |
Different forms have been described: | NLM/GHR:GBE1 OMIM:GBE1 NLM/GHR:GSDIV OMIM:GSDIV GARD:GSDIV ORPHA:GSDIV | ||
| Glycogenesis step 4 Glycogen branching enzyme |
GBE1: Nerve cells Adult polyglucosan body disease (APBD) |
Neuropathy, affecting the central and peripheral nervous systems. Cognitive impairment, pyramidal tetraparesis, peripheral neuropathy, and neurogenic bladder. Peripheral neuropathy and progressive muscle weakness and stiffness (spasticity). Cerebellar dysfunction and extrapyramidal signs in some. Late-onset, slowly progressive. | NLM/GHR:GBE1 OMIM:GBE1 NLM/GHR:APBD OMIM:APBD GARD:APBD ORPHA:APBD | ||
| De novo glycogen synthesis Glycogenin |
GYG1: Muscle GSD type XV (GSD 15, glycogenin deficiency) Polyglucosan body myopathy type 2 (PGBM2) |
GSD 15: Myopathy, cardiomyopathy. Rare. Muscle weakness. PGBM2: Myopathy. Proximal muscle weakness of the lower limbs, gait disturbances. Upper limbs and/or distal muscle weakness in some. Onset-age highly variable, slowly progressive. |
NLM/GHR:GYG1 OMIM:GYG1 OMIM:GSDXV ORPHA:GSDXV OMIM:PGBM2 ORPHA:PGBM2 |
Glycogenolysis
[edit]Current version at: Inborn errors of carbohydrate metabolism#Glycogenolysis
| Glycogenolysis step – Enzyme |
Gene: Organ(s) Disease (Synonyms) |
Reported symptoms. Forms (if applicable) Note: Not all patients have all symptoms; severity and presentation can vary. |
Diagnostic tests | Treatment | References and links |
|---|---|---|---|---|---|
| Glycogenolysis step: debranching – Glycogen debranching enzyme (GDE) |
AGL: Liver, muscles GSD type III (GSD 3, Forbes disease, Cori disease, limit dextrinosis, glycogen debrancher deficiency, GDE deficiency, AGL deficiency) |
Infant or child onset, often at puberty some symptoms improve. Liver: Hepatomegaly, growth retardation, hyperlipidemia, hypoglycemia. Occasional seizures related to hypoglycemia. Adult cirrhosis in some. Muscle: Myopathy, muscular hypotonia, muscle wasting (distal, some limb-girdle, some proximal instead), hypertrophic cardiomyopathy. Slowly progressive muscle weakness. GSD IIIa: Liver and muscle GSD IIIb: Liver only GSD IIIc: Liver only? GSD IIId: ? Muscle only form observed. |
NLM/GHR:AGL OMIM:AGL NLM/GHR:GSDIII OMIM:GSDIII GARD:GSDIII ORPHA:GSDIII | ||
| Glycogenolysis step: Release of glucose-1-phosphate (G-1-P) – Glycogen phosphorylase |
PYGL: Liver GSD type VI (GSD 6, Hers disease, hepatic glycogen phosphorylase deficiency, liver phosphorylase deficiency syndrome) |
Hepatomegaly, failure to thrive, growth retardation. No other developmental delay, no muscle involvement. Hypoglycemia, lactic acidosis, hyperlipidemia and ketosis during prolonged fasting periods. Infancy or childhood onset, symptoms tend to improve with age. | NLM/GHR:PYGL OMIM:PYGL NLM/GHR:GSD6 OMIM:GSD6 GARD:GSD6 ORPHA:GSD6 | ||
| Glycogenolysis step: Release of glucose-1-phosphate (G-1-P) – Glycogen phosphorylase |
PYGM: Muscle GSD type V (GSD 5, McArdle's disease, muscle phosphorylase deficiency, myophosphorylase deficiency, PYGM deficiency) |
Myopathy: Exercise intolerance, symptoms tend to improve with rest. "Second wind" phenomenon in most. Rhabdomyolysis and myoglobinuria possible. Progressive muscle weakness worsens in two-thirds of affected individuals, however in some the muscle weakness is stable. Onset forms: infant, child, adult. Infant-form most severe (e.g. progressive respiratory failure), adult-onset can be very mild (e.g. mainly poor stamina). |
NLM/GHR:PYGM OMIM:PYGM NLM/GHR:GSDV OMIM:GSDV GARD:GSDV ORPHA:GSDV |
Exercise intolerance: fatigue, muscle pain, and cramps during the first few minutes of exercise.
Glycolysis qwer
[edit]Glycolysis other
[edit]- ADH1B ADH1B
- ADH5 ADH5
- AKR1A1 AKR1A1
- ALDH2 ALDH2
- ALDH7A1 ALDH7A1
- DLAT DLAT
- DLD DLD
- FBP1 FBP1
- GOT2 GOT2
- HK1 HK1
- HK3 HK3
- MDH1 MDH1
- MDH2 MDH2
- PCK2 PCK2
- PDHA1 PDHA1
- PDHB PDHB
- PKM PKM PYRUVATE KINASE, MUSCLE;
- SLC2A1 SLC2A1
Glycolysis
[edit]Current version at: Inborn errors of carbohydrate metabolism#Glycolysis
| Glycolytic step Enzyme |
Gene: Organ(s) Disease (Synonyms) |
Reported symptoms Forms (if applicable) |
Diagnostic tests | Treatment | References and links |
|---|---|---|---|---|---|
| Glycolysis step 1 Glucokinase |
GCK: Pancreatic beta cells Hyperinsulinemic hypoglycemia, familial, 3 (HHF3, hyperinsulinism due to glucokinase deficiency) |
Hypoglycemia due to hyperinsulinemia. | NLM/GHR:GCK OMIM:HHF3 GARD:HHF3 ORPHA:HHF3 | ||
| Glycolysis step 1 Glucokinase |
GCK: Pancreatic beta cells Maturity onset diabetes of the young type II (MODY2, GCK-MODY) |
Hyperglycemia due to hypoinsulinemia while fasting, but some glucose tolerance when consuming carbohydrates. | NLM/GHR:GCK OMIM:MODY2 GARD:MODY2 ORPHA:MODY2 | ||
| Glycolysis step 2 Glucose-6-phosphate isomerase |
GPI: RBCs Glucose-6-phosphate isomerase deficiency (GPI deficiency, GPID, hemolytic anemia due to glucophosphate isomerase deficiency) |
Hemolytic anemia. | NLM/GHR:GPI OMIM:GPI NLM/GHR:GPID OMIM:GPID ORPHA:GPID | ||
| Glycolysis step 3 Phosphofructo-kinase 1 |
PFKM: Muscle, also RBCs PFKL: Liver, also RBCs GSD type VII (GSD 7, Tarui's Disease, Phosphofructokinase deficiency) |
Classic form: Symptoms usually appear in early childhood. Myopathy. Exercise-induced muscle cramps, weakness and sometimes rhabdomyolysis. Nausea and vomiting following strenuous exercise. Myoglobinuria, haemolytic anaemia, Hyperuricemia is common. High levels of bilirubin and jaundiced appearance possible. Late-onset form: Presents later in life. Myopathy, weakness and fatigue. Severe symptoms from classic type are absent. Infantile form: Rare. Often floppy infant syndrome (hypotonia), arthrogryposis, encephalopathy, cardiomyopathy and respiratory issues. Also central nervous system manifest possible, usually seizures. Hemolytic form: The defining characteristic is hemolytic anemia. Myopathy not as common. |
NLM/GHR:PFKM OMIM:PFKM OMIM:PFKL NLM/GHR:GSD VII OMIM:GSD VII GARD:GSD VII ORPHA:GSD VII | ||
| Glycolysis step 4 Aldolase A |
ALDOA: Muscle, also liver and RBCs GSD type XII (GSD 12, Aldolase A deficiency, ALDOA deficiency, red cell aldolase deficiency) |
Muscle Symptoms: Myopathy. Exercise intolerance, cramps. In some Rhabdomyolysis. Liver Symptoms: In some Hepatomegaly RBC Symptoms: Hemolytic anemia. |
NLM/GHR:ALDOA OMIM:ALDOA OMIM:GSD XII GARD:GSD XII ORPHA:GSD XII | ||
| Glycolysis step 4 Aldolase B |
ALDOB: Liver Hereditary fructose intolerance (Aldolase B deficiency, ALDOB deficiency) |
Hypoglycemia. Hepatic and renal dysfunction. | NLM/GHR:ALDOB OMIM:ALDOB NLM/GHR:ALDOB D OMIM:ALDOB D GARD:ALDOB D ORPHA:ALDOB D | ||
| Glycolysis step 4 Aldolase C |
ALDOC: Brain Unclear role in: |
Neurodegeneration. | See respective conditions | See respective conditions | OMIM:ALDOC |
| Glycolysis step 5 Triosephosphate isomerase |
TPI1: RBCs Triosephosphate isomerase deficiency (TPID) |
Hemolytic anemia. Reticulocytosis and hyperbilirubinemia are common. Classical generalized form: Progressive neurologic dysfunction with dystonia, tremor, dyskinesia, pyramidal tract signs, cardiomyopathy and spinal motor neuron involvement with progressive neuromuscular impairment (severe weakness and muscle wasting). |
NLM/GHR:TPI1 OMIM:TPI1 NLM/GHR:TPID OMIM:TPID GARD:TPID ORPHA:TPID | ||
| Glycolysis step 6 Glyceraldehyde 3-phosphate dehydrogenase (From here also Ribose-Metabolism) |
GAPDH: Brain Unclear role in: |
Neurodegeneration. | See respective conditions | See respective conditions | OMIM:GAPDH |
| Glycolysis step 7 Phosphoglycerate kinase |
PGK1: Muscle, RBCs Phosphoglycerate kinase deficiency (PGK1D, PGK deficiency, GSD due to phosphoglycerate kinase 1 deficiency) |
Myopathic form: Progressive muscle weakness, pain, and cramping, particularly with exercise. Myoglobinuria possible. Hemolytic form: Hemolytic anemia. Progressive neurologic impairment in some. Combinations of both forms have been reported. |
NLM/GHR:PGK1 OMIM:PGK1 NLM/GHR:PGK1D OMIM:PGK1D GARD:PGK1D ORPHA:PGK1D | ||
| Glycolysis step 8 Phosphoglycerate mutase |
PGAM2: Muscle GSD type X (GSD 10, muscle phosphoglycerate mutase deficiency, myopathy due to PGAM deficiency, PGAMD) |
Myopathy, exercise intolerance. Exercise-induced cramps, myoglobinuria and myalgia. Rhabdomyolysis possible. | NLM/GHR:PGAM2 OMIM:PGAM2 NLM/GHR:GSD X OMIM:GSD X GARD:GSD X ORPHA:GSD X | ||
| Glycolysis step 9 Enolase 1 (Alpha-enolase, α-enolase) |
ENO1: RBCs Enolase deficiency (α-enolase deficiency, alpha-enolase deficiency) |
Hemolytic anemia. | OMIM:ENO1 | ||
| Glycolysis step 9 Enolase 1 (Alpha-enolase, α-enolase) |
ENO1 Unclear role in: |
Autoimmunity. | See respective conditions | See respective conditions | OMIM:ENO1 |
| Glycolysis step 9 Enolase 3 (Beta-enolase, β-enolase) |
ENO3: Muscle GSD type XIII (GSD 13, β-enolase deficiency, beta-enolase deficiency, enolase 3 deficiency, muscle enolase deficiency) |
Myopathy. Exercise-induced myalgias, generalized muscle weakness and fatigability. | NLM/GHR:ENO3 OMIM:ENO3 OMIM:GSD XIII GARD:GSD XIII ORPHA:GSD XIII | ||
| Glycolysis step 10 Pyruvate kinase |
PKLR: RBCs, liver Pyruvate kinase deficiency (PK deficiency, PKD) |
Hemolytic anemia. | NLM/GHR:PKLR OMIM:PKLR NLM/GHR:PKD OMIM:PKD GARD:PKD ORPHA:PKD |
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[edit]Gluconeogenesis
[edit]| Gluconeogenesis step – Enzyme
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Gene: Organ(s) Disease (Synonyms) |
Reported symptoms. Forms (if applicable) Note: Not all patients have all symptoms; severity and presentation can vary. |
Diagnostic tests | Treatment | References and links |
|---|---|---|---|---|---|
| Gluconeogenesis final step: Conversion of G-1-P to glucose – Glucose 6-phosphatase
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G6PC: Liver SLC37A4 (G6PT1): Liver GSD type I (GSD 1, von Gierke's disease, hepatorenal glycogenosis, glucose-6-phosphate deficiency, glucose-6-phosphate transport defect) |
Hypoglycemia and hepatomegaly. Growth retardation, delayed puberty, lactic acidemia, hyperlipidemia, hyperuricemia. In adults hepatic adenomas likely. | NLM/GHR:G6PC OMIM:G6PC NLM/GHR:SLC37A4 OMIM:SLC37A4 NLM/GHR:GSD 1 ORPHA:GSD 1 OMIM:GSD 1a GARD:GSD 1a ORPHA:GSD 1a OMIM:GSD 1b GARD:GSD 1b ORPHA:GSD 1b OMIM:GSD 1c/1d | ||
| Gluconeogenesis final step: Conversion of G-1-P to glucose – Glucose 6-phosphatase
|
G6PC3: WBCs, heart, others Severe congenital neutropenia type 4 (SCN4, congenital agranulocytosis, congenital neutropenia, Kostmann's disease, severe congenital neutropenia-pulmonary hypertension-superficial venous angiectasis) Dursun syndrome (DURSS, pulmonary arterial hypertension-leukopenia-atrial septal defect syndrome) |
SCN4: A disorder of hematopoiesis. Maturation arrest of granulopoiesis at the level of promyelocytes. Neutropenia. Osteopenia, may lead to osteoporosis. Prone to recurrent infections. In some heart and genital abnormalities, cancerous conditions of the blood, seizures, developmental delay. Dursun syndrome: Pulmonary arterial hypertension, cardiac abnormalities (including secundum-type atrial septal defect), intermittent neutropenia, lymphopenia, monocytosis and anemia. |
NLM/GHR:G6PC3 OMIM:G6PC3 NLM/GHR:SCN4 OMIM:SCN4 ORPHA:SCN4 ORPHA:DURSS
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| Gluconeogenesis step 8 – Fructose 1,6-bisphosphatase
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FBP1: Organ Fructose bisphosphatase deficiency (FBP1, Baker-Winegrad disease) |
Fasting hypoglycemia with lactic acidosis. Episodes of hyperventilation, apnea, and ketosis. | NLM/GHR:FBP1 OMIM:FBP1 OMIM:FBP1D GARD:FBP1D ORPHA:FBP1D
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Related to glycolysis
[edit]| Related enzymatic function – Enzyme (Relation) |
Gene: Organ(s) Disease (Synonyms) |
Reported symptoms. Forms (if applicable) Note: Not all patients have all symptoms; severity and presentation can vary. |
Diagnostic tests | Treatment | References and links |
|---|---|---|---|---|---|
| Inter-conversion of pyruvate and lactate. – Lactate dehydrogenase A
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LDHA: Muscle GSD type XI (GSD 11, lactate dehydrogenase deficiency, LDH deficiency) |
Myopathy. Exercise intolerance. Note: Deficiency of dehydrogenase-B (LDHB) has been observed as asymptomatic. |
NLM/GHR:LDHA OMIM:LDHA NLM/GHR:GSD 11 OMIM:GSD 11 ORPHA:GSD 11 ORPHA:GSD 11 |
Related to glycogenolysis
[edit]Glycogenosis Current version at: Inborn errors of carbohydrate metabolism#Related_to_glycogenolysis
| Related enzymatic function ⁓ Enzyme (Relation) |
Gene: Organ(s) Disease (Synonyms) |
Reported symptoms. Forms (if applicable) Note: Not all patients have all symptoms; severity and presentation can vary. |
Diagnostic tests | Treatment | References and links |
|---|---|---|---|---|---|
| Glycogenolysis step: Release of G-1-P ⁓ Phosphorylase kinase, alpha 1 (Activation of glycogen phosphorylase, PYGL) |
PHKA2: Liver (GSD 9a) PHKB: Liver, Muscle (GSD 9b) PHKG2: Liver (GSD 9c) GSD type IX |
GSD 9a: Liver form. Hepatomegaly, growth retardation, elevation of glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase, hypercholesterolemia, hypertriglyceridemia, and fasting hyperketosis. Improves with age, most adult patients are asymptomatic. GSD 9a1: PhK deficiency in erythrocytes. GSD 9a2: Normal PhK activity in erythrocytes. GSD 9c: More severe than 9a. In some hepatic fibrosis or cirrhosis. GSD 9b: Liver and muscle form. Additionally mild myopathy like GSD 9d. Rare. |
Diagnose | Treatment | NLM/GHR:PHKA2 OMIM:PHKA2 NLM/GHR:PHKB OMIM:PHKB NLM/GHR:PHKG2 OMIM:PHKG2 NLM/GHR:GSD 9 ORPHA:GSD 9 OMIM:GSD 9a1/9a2 ORPHA:GSD 9a/9c OMIM:GSD 9b ORPHA:GSD 9b OMIM:GSD 9c |
| Glycogenolysis step: Release of G-1-P ⁓ Phosphorylase kinase, alpha 1 (Activation of glycogen phosphorylase, PYGM) |
PHKA1: Muscle GSD type IXd (GSD 9d, phosphorylase b kinase deficiency, PhK deficiency, muscle glycogenosis) |
Myopathy. Exercise-induced muscle weakness or stiffness. Relative mild compared to other metabolic myopathies. Adult-onset, some asymptomatic in late adulthood. | Diagnose | Treatment | NLM/GHR:PHKA1 OMIM:PHKA1 NLM/GHR:GSD 9 OMIM:GSD 9d ORPHA:GSD 9d/9e |
| Degradation of glycogen to glucose in lysosomes ⁓ Acid alpha-glucosidase
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GAA: Myopathy GSD type II (GSD 2, Pompe's disease, acid maltase deficiency, deficiency of lysosomal alpha-glucosidase, cardiomegalia glycogenica) |
Classic infantile form (Pompe disease): Cardiomyopathy and muscular hypotonia. In some respiratory involvement. Juvenile and adult form:: Myopathy of the skeletal muscles. Some similarity to limb-girdle dystrophy. In some respiratory involvement. Non-classic infantile form: Less severe. |
Diagnose | Treatment | NLM/GHR:GAA OMIM:GAA NLM/GHR:GSD 2 OMIM:GSD 2 GARD:GSD 2 ORPHA:GSD 2
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