Browsing Pathways

Fumarase deficiency, also called fumaric aciduria, is a rare inborn error of metabolism (IEM) and autosomal recessive metabolic disorder caused by a defective mitochondrial fumarate hydratase. Fumarate hydratase catalyzes the conversion of fumaric acid into L-Malic acid or other way around. This disorder is characterized by a large accumulation of fumaric acid in the mitochondrial. Symptoms of the disorder include microcephaly (i.e. small head), severe developmental delay, hypotonia (i.e. weak muscle), and etc. Treatment with oral malic acid is very effective since malic acid can keep the Krebs cycle to function. Fumarase deficiency has been reported in approximately 100 people.

GM2 gangliosidosis varient B or Tay-Sachs disease(TSD) is a neurodegenerative disorder which causes death in infantiles by age 5. Symptoms of TSD are present within 6 months of birth and include lack of motor development, mental retardation, seizures, and ultimately death. TSD is caused by the accumulation of GM2 gangliosides. Hexosaminadase A is the enzyme responsible for the degradation of GM2 gangliosides. It is a heterodimer made an alpha and beta subunit. The deficiency of this enzyme leads to the accumulation of GM2 gangliosides in neuronal lysosomes, eventually leading to cell death

GABA-transaminase deficiency, also known as gamma-amino butyric acid transaminase (GABA-T) deficiency, is an extremely rare autosomal recessive inborn error of metabolism (IEM) that is caused by a defect in the ABAT gene, which codes for 4-aminobutyrate (GABA) aminotransferase. This enzyme is present in several tissues in addition to brain and is most active in liver, and it catalyzes the conversion of GABA and 2-oxoglutarate into succinic semialdehyde and L-glutamate, and when it is deficient, GABA levels in the body, specifically the cerebrospinal fluid, are elevated. GABA is a neurotransmitter found in the nervous system that inhibits neurons from firing, and also affects the development of the brain, as well as regulating muscle tone. GABA-T can also convert beta-alanine and oxoglutaric acid to L-glutamic acid and malonic semialdehyde as part of the beta-alanine metabolism pathway, and when it is mutated, leads to an accumulation of beta-alanine within the cell. GABA-T deficiency is characterized by an increase of GABA levels in the cerebrospinal fluid. Symptoms of this disorder include low muscle tone and psychomotor retardation, as well as potential epilepsy and excessive sleeping. Treatment with Flumanezil, sold as Anexate, Lanexat, Mazicon or Romazicon, a GABA-A antagonist, has been tested and may be beneficial in some cases, and potentially more effective if started at a young age. It is estimated that GABA-T deficiency affects less than 1 in 1,000,000 individuals, as only five cases have been reported in literature as of 2017.

GABA-transaminase deficiency, also known as gamma-amino butyric acid transaminase (GABA-T) deficiency, is an extremely rare autosomal recessive inborn error of metabolism (IEM) that is caused by a defect in the ABAT gene, which codes for 4-aminobutyrate (GABA) aminotransferase. This enzyme is present in several tissues in addition to brain and is most active in liver, and it catalyzes the conversion of GABA and 2-oxoglutarate into succinic semialdehyde and L-glutamate, and when it is deficient, GABA levels in the body, specifically the cerebrospinal fluid, are elevated. GABA is a neurotransmitter found in the nervous system that inhibits neurons from firing, and also affects the development of the brain, as well as regulating muscle tone. GABA-T can also convert beta-alanine and oxoglutaric acid to L-glutamic acid and malonic semialdehyde as part of the beta-alanine metabolism pathway, and when it is mutated, leads to an accumulation of beta-alanine within the cell. GABA-T deficiency is characterized by an increase of GABA levels in the cerebrospinal fluid. Symptoms of this disorder include low muscle tone and psychomotor retardation, as well as potential epilepsy and excessive sleeping. Treatment with Flumanezil, sold as Anexate, Lanexat, Mazicon or Romazicon, a GABA-A antagonist, has been tested and may be beneficial in some cases, and potentially more effective if started at a young age. It is estimated that GABA-T deficiency affects less than 1 in 1,000,000 individuals, as only five cases have been reported in literature as of 2017.

Galactosemia (GALT Deficiency; GALT; Galactose-1-Phosphate Uridylyltransferase Deficiency) is a rare genetic disorder caused by a mutation in the GALT gene which codes for galactose-1-phosphate uridylyltransferase. A deficiency in this enzyme results in accumulation of D-galactose and galactitol in plasma and urine; bilirubin, chloride, and galactose-1-phosphate, and transaminases in serum. Symptoms, which present at birth, include jaundice, enlarged liver, anemia, weight loss, and vomiting. Treatment includes galactose-free diet, antibiotics, and vitamin K.

Galactosemia (GALT Deficiency; GALT; Galactose-1-Phosphate Uridylyltransferase Deficiency) is a rare genetic disorder caused by a mutation in the GALT gene which codes for galactose-1-phosphate uridylyltransferase. A deficiency in this enzyme results in accumulation of D-galactose and galactitol in plasma and urine; bilirubin, chloride, and galactose-1-phosphate, and transaminases in serum. Symptoms, which present at birth, include jaundice, enlarged liver, anemia, weight loss, and vomiting. Treatment includes galactose-free diet, antibiotics, and vitamin K.

Galactokinase deficiency also called Galactosemia type II, is a rare inborn error of metabolism (IEM) and an autosomal recessive disorder of galactokinase caused by a mutation in the GALK1 gene on chromosome 17q24. Galactokinase uses 1 ATP to catalyse the phosphorylation of α-D-galactose to galactose 1-phosphate and catalyses β-D-galactose to glucose 1-phosphate. Symptoms include cataract formation in children who are exposed to lactose in their diets. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens. Treatment includes immediately removing lactose from patient’s diet, however symptoms such as delayed speech, cognitive learning and motor skills can still be present.

Galactokinase deficiency also called Galactosemia type II, is a rare inborn error of metabolism (IEM) and an autosomal recessive disorder of galactokinase caused by a mutation in the GALK1 gene on chromosome 17q24. Galactokinase uses 1 ATP to catalyse the phosphorylation of α-D-galactose to galactose 1-phosphate and catalyses β-D-galactose to glucose 1-phosphate. Symptoms include cataract formation in children who are exposed to lactose in their diets. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens. Treatment includes immediately removing lactose from patient’s diet, however symptoms such as delayed speech, cognitive learning and motor skills can still be present.

Galactosemia III also called GALE deficiency or UDP-Galactose-4-Epimerase deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by either a homozygous or compound heterozygous mutation in the UDP-galactose-4-epimerase (GALE) gene. GALE catalyses the reversible conversion of UDP-galactose to UDP-glucose in galactose metabolism. Symptoms are similar to classic galactosemia, including jaundice, vomiting, hypotonia, failure to thrive, hepatomegaly, moderate generalized amino aciduria and marked galactosuria. Treatment usually includes galactose restricted diets instead of galactose free diets in the management of this disorder because unlike patients with galactokinase deficiency and classic galactosemia, patients with galactose epimerase deficiency cannot utilize the endogenous pathway for synthesis of UDP-galactose. This makes patients dependent on exogenous galactose.

Galactosemia III also called GALE deficiency or UDP-Galactose-4-Epimerase deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by either a homozygous or compound heterozygous mutation in the UDP-galactose-4-epimerase (GALE) gene. GALE catalyses the reversible conversion of UDP-galactose to UDP-glucose in galactose metabolism. Symptoms are similar to classic galactosemia, including jaundice, vomiting, hypotonia, failure to thrive, hepatomegaly, moderate generalized amino aciduria and marked galactosuria. Treatment usually includes galactose restricted diets instead of galactose free diets in the management of this disorder because unlike patients with galactokinase deficiency and classic galactosemia, patients with galactose epimerase deficiency cannot utilize the endogenous pathway for synthesis of UDP-galactose. This makes patients dependent on exogenous galactose.