Browsing Pathways

Biotinidase deficiency (Multiple carboxylase deficiency) is an autosomal recessive disease caused by a mutation in the BTD gene which codes for biotinidase. A deficiency in this enzyme results in accumulation of ammonia and ketone bodies in blood; 3-hydroxyisovaleric acid in plasma, spinal fluid, and urine; hydroxypropionic acid, 2-hydroxybutyric acid, 3-Hydroxybutyric acid, and citric acid in spinal fluid; and 3-methylcrotonylglycine, hydroxypropionic acid, and L and D-lactic acid in urine. Symptoms, which can present from birth into adulthood include hypotonia, ketosis, hyperammonemia, motor retardation, coma, and seborrhoic skin rash. Treatment includes biotin.

Hereditary fructose intolerance, also called hereditary fructose-1-phosphate aldolase deficiency or hereditary fructosemia, is rare inborn error of metabolism (IEM) and autosomal recessive disorder of the fructose and mannose degradation pathway. It is caused by a mutation in the ALDOB gene, which encodes fructose-bisphosphatse aldolase B, also known as aldolase B or liver-type aldolase. This enzyme normally cleaves fructose 1,6-bisphosphate into dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate, isomers of one another that are later used in glycolysis. Hereditary fructose intolerance is characterized by an accumulation of fructose-1-phosphate in the liver, as well as a depletion of ATP due to glycolysis having less input than necessary. Symptoms of this disorder include hypoglycemia, abdominal pain and vomiting as well as other symptoms after ingesting fructose. After repeated ingestion of fructose, liver and kidney damage can occur, as well as growth retardation, seizures, and even death. Hereditary fructose intolerance can be treated by eliminating fructose from the diet, and multivitamins can be prescribed to make up for the lack of fruits, a major source of fructose, in the diet. It is estimated that hereditary fructose intolerance affects 1 in between 20,000 and 30,000 individuals.

Fructosuria, full name essential fructosuria, is a condition that presents no symptoms and is benign. Patients with this condition exhibit a mutation in the KHK gene, which leads to fructose metabolism not being completed. This is because of a lack of the enzyme fructokinase, found in the liver. It is identified by the presence of fructose in the urine, which in people without the condition should not be present.

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.

Primary hyperolaria type 2 (PH2) is a rare condition resulting from glyoxylate reductase/hydroxypyruvate reductase (GR/HPR) enzyme deficiency. PH2 results in calcium oxalate (also known as oxalic acid) deposits and end-stage renal disease. These deposits may cause kidney damage or failure.

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 Decarboxylase E1 Component Deficiency is caused by a defect in the PDHA1 gene which codes for mitochondrial pyruvate dehydrogenase E1 component subunit alpha, somatic form. This is a homotetrameric enzyme that catalyses the decarboxylation of pyruvic acid to acetaldehyde and carbon dioxide. A defect in this enzyme results in accumulation of lacate and pyruvate. Symptoms and signs include severe lactic acidosis in the newborns that usually leading to death, hypotonic, lethargic, seizures, mental retardation and spasticity.

Leigh Syndrome, also called Leigh Disease or infantile subacute necrotizing encephalopathy, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder that is caused by a mutation of any one of 75 different genes. Disruptions of the complexes I or IV are the most common reasons for Leigh syndrome. Complex IV is crucial in the electron transfer steps of oxidative phosphorylation, which is needed to provide energy to the mitochondria. This disorder is characterized by a large accumulation of lactate in the body. Symptoms of the disorder include diarrhea, dysphagia and vomiting. There is no cure for Leigh syndrome and the loss motor skills degenerate rapidly. It is estimated that Leigh syndrome affects 1 in 40,000 individuals.

Carbamoyl Phosphate Synthetase Deficiency, also called hyperammonemia due to carbamoyl phosphate synthetase 1 deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the urea cycle caused by a defective CPS1 gene. The CPS1 gene codes for the protein carbamoyl phosphate synthetase I, which plays a role in the urea cycle. This disorder is characterized by a large accumulation of ammonia in the blood. Symptoms of the disorder include unusual movements, seizures, unusual sleeping or coma. Treatment with citrulline or arginine, which maintains a regular rate of protein creation. It is estimated that carbamoyl phosphate synthetase deficiency affects 1 in 800,000 individuals in Japan.

Ornithine transcarbamylase deficiency (OTC deficiency), is a rare inborn error of metabolism (IEM) and X-linked disorder of the urea cycle caused by a deficiency of ornithine transcarbamylase. Ornithine transcarbamylase is responsible for processing nitrogen produced by the urea cycle. This disorder is characterized by a large accumulation of ammonia in the bloodstream. Symptoms of the disorder include lethargy, seizures, or coma. Treatment with hemodialysis is very effective in patients with high ammonia blood levels. It is estimated that ornithine transcarbamylase deficiency affects 1 in 14,000 to 1 in 77,000 individuals. These estimates are very different because adults with the late-onset form of ornithine transcarbamylase deficiency are less likely to come to medical attention.