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User:Tony Mach/inborn

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By affected system

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Digestion

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Lactose intolerance.

Fructose malabsorption.

...

Overview of intracellular carbohydrate metabolism

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UDP-glucose 4-epimerase

Glycogenesis

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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

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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

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Glycolysis other

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Glycolysis

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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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Gluconeogenesis

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Gluconeogenesis 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
Gluconeogenesis final step:
Conversion of G-1-P to glucose
Glucose 6-phosphatase
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


Gluconeogenesis step 8
Fructose 1,6-bisphosphatase
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 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
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
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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 9, phosphorylase b kinase deficiency, PhK deficiency, liver glycogenosis)
Formerly GSD type VIII (GSD 8)

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
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