Pathways

Pyruvate dehydrogenase complex deficiency results from a mutation in the E1-alpha polypeptide gene (PDHA1). PDHA1 encodes the pyruvate dehydrogenase complex (PDC) a critical complex that converts pyruvate from glycolysis to acetyl CoA for the citric acid cycle. This conversion step links glycolysis and the citric acid cycle. A defect in this complex causes accumulation of lactate and pyruvate in the blood; lactate and pyruvic acid in the spinal fluid; and lactate in the urine. Symptoms include lactic and metabolic acidosis, motor retardation, dystonia, growth and mental retardation, and respiratory distress.

Pyruvate Dehydrogenase (PDH) Deficiency is an X linked disease where individuals have a reduced number of functioning PDH complexes ultimately affecting the mitochondria’s energy metabolism. In a healthy individual, PDH complex catalyzes the conversion of pyruvate to acetyl coenzyme A, therefore PDH deficiency can cause the accumulation of excess pyruvate and lactic acid. PDH deficiency presents itself in a variety of ways, however since the brain obtains most of it’s energy from aerobic oxidation of glucose, all PDH deficient individuals have some degree of neurological impairment. Other symptoms range from fatal lactic acidosis in the newborns, chronic neurodegenerative conditions, brain lesions, cerebral atrophy and much more. Due to the fatal nature of the disease many with this condition do not live past childhood, however there are some that survive to adolescents and adulthood. Treatments have tried to minimize systemic lactic acid accumulation by feeding patients high fat/low carbohydrate diets. However, this does not reverse neurological structural damage already present and therefore does little to influence the end results.

Pyruvate Dehydrogenase (PDH) Deficiency is an X linked disease where individuals have a reduced number of functioning PDH complexes ultimately affecting the mitochondria’s energy metabolism. In a healthy individual, PDH complex catalyzes the conversion of pyruvate to acetyl coenzyme A, therefore PDH deficiency can cause the accumulation of excess pyruvate and lactic acid. PDH deficiency presents itself in a variety of ways, however since the brain obtains most of it’s energy from aerobic oxidation of glucose, all PDH deficient individuals have some degree of neurological impairment. Other symptoms range from fatal lactic acidosis in the newborns, chronic neurodegenerative conditions, brain lesions, cerebral atrophy and much more. Due to the fatal nature of the disease many with this condition do not live past childhood, however there are some that survive to adolescents and adulthood. Treatments have tried to minimize systemic lactic acid accumulation by feeding patients high fat/low carbohydrate diets. However, this does not reverse neurological structural damage already present and therefore does little to influence the end results.

Pyruvate Dehydrogenase (PDH) Deficiency is an X linked disease where individuals have a reduced number of functioning PDH complexes ultimately affecting the mitochondria’s energy metabolism. In a healthy individual, PDH complex catalyzes the conversion of pyruvate to acetyl coenzyme A, therefore PDH deficiency can cause the accumulation of excess pyruvate and lactic acid. PDH deficiency presents itself in a variety of ways, however since the brain obtains most of it’s energy from aerobic oxidation of glucose, all PDH deficient individuals have some degree of neurological impairment. Other symptoms range from fatal lactic acidosis in the newborns, chronic neurodegenerative conditions, brain lesions, cerebral atrophy and much more. Due to the fatal nature of the disease many with this condition do not live past childhood, however there are some that survive to adolescents and adulthood. Treatments have tried to minimize systemic lactic acid accumulation by feeding patients high fat/low carbohydrate diets. However, this does not reverse neurological structural damage already present and therefore does little to influence the end results.

Pyruvate Dehydrogenase (PDH) Deficiency is an X linked disease where individuals have a reduced number of functioning PDH complexes ultimately affecting the mitochondria’s energy metabolism. In a healthy individual, PDH complex catalyzes the conversion of pyruvate to acetyl coenzyme A, therefore PDH deficiency can cause the accumulation of excess pyruvate and lactic acid. PDH deficiency presents itself in a variety of ways, however since the brain obtains most of it’s energy from aerobic oxidation of glucose, all PDH deficient individuals have some degree of neurological impairment. Other symptoms range from fatal lactic acidosis in the newborns, chronic neurodegenerative conditions, brain lesions, cerebral atrophy and much more. Due to the fatal nature of the disease many with this condition do not live past childhood, however there are some that survive to adolescents and adulthood. Treatments have tried to minimize systemic lactic acid accumulation by feeding patients high fat/low carbohydrate diets. However, this does not reverse neurological structural damage already present and therefore does little to influence the end results.

Dihydrolipoamide dehydrogenase deficiency, which is also known as DLDD, DLD, E3 deficiency, pyruvate dehydrogenase E3 deficiency, DLD deficiency, E3-deficient maple syrup urine disease, is a rare inherited inborn error of metabolism. DLD deficiency occurs in an estimated 1 in 35 000 to 48 000 individuals of Ashkenazi Jewish descent. DLDD is an autosomal recessive metabolic disorder characterized by mutations to the DLD gene, which codes for dihydrolipoamide dehydrogenase (DLD). DLD is a flavoprotein enzyme that oxidizes dihydrolipoamide to lipoamide. The DLD homodimer functions as the E3 component of the pyruvate, alpha-ketoglutarate, and branched-chain amino acid-dehydrogenase complexes and the glycine cleavage system, all of which are located in the mitochondrial matrix. DLDD is a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate. E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD) and is sometimes referred to as MSUD type III, although patients with E3 deficiency have additional biochemical defects.

Dihydrolipoamide dehydrogenase deficiency, which is also known as DLDD, DLD, E3 deficiency, pyruvate dehydrogenase E3 deficiency, DLD deficiency, E3-deficient maple syrup urine disease, is a rare inherited inborn error of metabolism. DLD deficiency occurs in an estimated 1 in 35 000 to 48 000 individuals of Ashkenazi Jewish descent. DLDD is an autosomal recessive metabolic disorder characterized by mutations to the DLD gene, which codes for dihydrolipoamide dehydrogenase (DLD). DLD is a flavoprotein enzyme that oxidizes dihydrolipoamide to lipoamide. The DLD homodimer functions as the E3 component of the pyruvate, alpha-ketoglutarate, and branched-chain amino acid-dehydrogenase complexes and the glycine cleavage system, all of which are located in the mitochondrial matrix. DLDD is a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate. E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD) and is sometimes referred to as MSUD type III, although patients with E3 deficiency have additional biochemical defects.

Dihydrolipoamide dehydrogenase deficiency, which is also known as DLDD, DLD, E3 deficiency, pyruvate dehydrogenase E3 deficiency, DLD deficiency, E3-deficient maple syrup urine disease, is a rare inherited inborn error of metabolism. DLD deficiency occurs in an estimated 1 in 35 000 to 48 000 individuals of Ashkenazi Jewish descent. DLDD is an autosomal recessive metabolic disorder characterized by mutations to the DLD gene, which codes for dihydrolipoamide dehydrogenase (DLD). DLD is a flavoprotein enzyme that oxidizes dihydrolipoamide to lipoamide. The DLD homodimer functions as the E3 component of the pyruvate, alpha-ketoglutarate, and branched-chain amino acid-dehydrogenase complexes and the glycine cleavage system, all of which are located in the mitochondrial matrix. DLDD is a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate. E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD) and is sometimes referred to as MSUD type III, although patients with E3 deficiency have additional biochemical defects.

Dihydrolipoamide dehydrogenase deficiency, which is also known as DLDD, DLD, E3 deficiency, pyruvate dehydrogenase E3 deficiency, DLD deficiency, E3-deficient maple syrup urine disease, is a rare inherited inborn error of metabolism. DLD deficiency occurs in an estimated 1 in 35 000 to 48 000 individuals of Ashkenazi Jewish descent. DLDD is an autosomal recessive metabolic disorder characterized by mutations to the DLD gene, which codes for dihydrolipoamide dehydrogenase (DLD). DLD is a flavoprotein enzyme that oxidizes dihydrolipoamide to lipoamide. The DLD homodimer functions as the E3 component of the pyruvate, alpha-ketoglutarate, and branched-chain amino acid-dehydrogenase complexes and the glycine cleavage system, all of which are located in the mitochondrial matrix. DLDD is a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate. E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD) and is sometimes referred to as MSUD type III, although patients with E3 deficiency have additional biochemical defects.

Pyruvate kinase deficiency is a genetic disorder. It affects red blood cells in the body. Patients are affected by a condition called chronic hemolytic anemia, which is where red blood cells undergo hemolysis before they are meant to which causes anemia in the patient. Symptoms of this condition can include jaundice, fatigue, dyspnea and splenomegaly. Gallstones are also common to patients with this disorder. This disorder is diagnosed through genetic testing. In mild cases, no treatment is required. Patients with more severe cases may require blood transfusions, and occasionally the spleen is removed to aid with the reduction of red blood cell destruction.