Browsing Pathways

3-beta-hydroxysteroid dehydrogenase (HSD) deficiency is an extremely rare inborn error of metabolism (IEM) and autosomal recessive disorder of the steroidogenesis pathway. It is caused by an defect in the HSD3B2 gene which encodes for the 3 beta-hydroxysteroid dehydrogenase enzyme, which is responsible for forming cortisol from 11b,17a,21-trihydroxypregnenolone. When the enzyme is not correctly produced, cortisol levels in the cell are lowered, and as cortisol is used in the production of other steroids, it may affect their levels as well. 3-beta-HSD deficiency is characterized by low levels of cortisol produced in the adrenal glands. Symptoms include abnormal genitalia for both males and females, as well as infertility. There is also a more severe salt-wasting form of this deficiency, characterized by dehydration. Treatment for 3-beta-HSD deficiency includes steroid replacement, as well as sex hormone replacement during puberty to allow proper development. Surgery can also be used to correct any genital abnormalities that may occur. It is estimated that 3-beta-HSD deficiency affects less than 1 in 1,000,000 individuals, with around 60 cases reported.

3-beta-hydroxysteroid dehydrogenase (HSD) deficiency is an extremely rare inborn error of metabolism (IEM) and autosomal recessive disorder of the steroidogenesis pathway. It is caused by an defect in the HSD3B2 gene which encodes for the 3 beta-hydroxysteroid dehydrogenase enzyme, which is responsible for forming cortisol from 11b,17a,21-trihydroxypregnenolone. When the enzyme is not correctly produced, cortisol levels in the cell are lowered, and as cortisol is used in the production of other steroids, it may affect their levels as well. 3-beta-HSD deficiency is characterized by low levels of cortisol produced in the adrenal glands. Symptoms include abnormal genitalia for both males and females, as well as infertility. There is also a more severe salt-wasting form of this deficiency, characterized by dehydration. Treatment for 3-beta-HSD deficiency includes steroid replacement, as well as sex hormone replacement during puberty to allow proper development. Surgery can also be used to correct any genital abnormalities that may occur. It is estimated that 3-beta-HSD deficiency affects less than 1 in 1,000,000 individuals, with around 60 cases reported.

3-beta-hydroxysteroid dehydrogenase (HSD) deficiency is an extremely rare inborn error of metabolism (IEM) and autosomal recessive disorder of the steroidogenesis pathway. It is caused by an defect in the HSD3B2 gene which encodes for the 3 beta-hydroxysteroid dehydrogenase enzyme, which is responsible for forming cortisol from 11b,17a,21-trihydroxypregnenolone. When the enzyme is not correctly produced, cortisol levels in the cell are lowered, and as cortisol is used in the production of other steroids, it may affect their levels as well. 3-beta-HSD deficiency is characterized by low levels of cortisol produced in the adrenal glands. Symptoms include abnormal genitalia for both males and females, as well as infertility. There is also a more severe salt-wasting form of this deficiency, characterized by dehydration. Treatment for 3-beta-HSD deficiency includes steroid replacement, as well as sex hormone replacement during puberty to allow proper development. Surgery can also be used to correct any genital abnormalities that may occur. It is estimated that 3-beta-HSD deficiency affects less than 1 in 1,000,000 individuals, with around 60 cases reported.

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (3-Hydroxy-3-methylglutaric acidemia; Leucine metabolism, defect in, HMG-CoA lyase deficiency) is an autosomal recessive disease caused by a mutation in the HMGCL gene which codes for hydroxymethylglutaryl-CoA lyase. A deficiency in this enzyme results in accumulation of 3-hydroxymethylglutaric acid, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine and 3-methylglutaconic acid (cis and trans form), and methylglutaric acid in urine; and ammonia in blood. Symptoms include cardiomyopathy, dehydration, hypotonia, lactic acidosis, and pancreatitis. Treatment includes a low-fat, low-protein, high-carbohydrate diet.

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (3-Hydroxy-3-methylglutaric acidemia; Leucine metabolism, defect in, HMG-CoA lyase deficiency) is an autosomal recessive disease caused by a mutation in the HMGCL gene which codes for hydroxymethylglutaryl-CoA lyase. A deficiency in this enzyme results in accumulation of 3-hydroxymethylglutaric acid, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine and 3-methylglutaconic acid (cis and trans form), and methylglutaric acid in urine; and ammonia in blood. Symptoms include cardiomyopathy, dehydration, hypotonia, lactic acidosis, and pancreatitis. Treatment includes a low-fat, low-protein, high-carbohydrate diet.

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (3-Hydroxy-3-methylglutaric acidemia; Leucine metabolism, defect in, HMG-CoA lyase deficiency) is an autosomal recessive disease caused by a mutation in the HMGCL gene which codes for hydroxymethylglutaryl-CoA lyase. A deficiency in this enzyme results in accumulation of 3-hydroxymethylglutaric acid, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine and 3-methylglutaconic acid (cis and trans form), and methylglutaric acid in urine; and ammonia in blood. Symptoms include cardiomyopathy, dehydration, hypotonia, lactic acidosis, and pancreatitis. Treatment includes a low-fat, low-protein, high-carbohydrate diet.

3-Hydroxyisobutyric acid dehydrogenase deficiency (3-hydroxyisobutyric aciduria) is an extremely rare inborn error of metabolism (IEM), potentially caused by numerous mechanisms. It is currently thought to be autosomal recessively inherited. At least two cases of 3-hydroxyisobutyric aciduria were determined to be caused by a mutation in the ALDH6A1 gene, which encodes acylating methylmalonate-semialdehyde dehydrogenase. This enzyme converts 2-methyl-3-oxopropanoate, CoA and water into propanoyl-CoA, using NAD+ as an oxidizing agent, and producing a hydrogen ion and hydrogencarbonate as byproducts. Other forms of 3-hydroxyisobutyric aciduria may be caused by a mutation in the gene encoding 3-hydroxyisobutyrate dehydrogenase, which forms (S)-methylmalonic acid semialdehyde from (S)-3-hydroxyisobutyric acid. This mutation leads to an accumulation of (S)-3-hydroxyisobutyric acid, as no other processes in the pathway use it. 3-hydroxyisobutyric aciduria is characterized by elevated levels of 3-hydroxyisobutyric acid excreted in the urine. Symptoms of the disorder include dysmorphic features, developmental delays and intellectual disabilities. Treatments are not currently well researched due to the rarity of the condition, but protein-restricted diets may be helpful. It is estimated that 3-hydroxyisobutyric aciduria affects less than 1 in 1,000,000 people, with only 12 cases having been reported by 2006.

3-Hydroxyisobutyric acid dehydrogenase deficiency (3-hydroxyisobutyric aciduria) is an extremely rare inborn error of metabolism (IEM), potentially caused by numerous mechanisms. It is currently thought to be autosomal recessively inherited. At least two cases of 3-hydroxyisobutyric aciduria were determined to be caused by a mutation in the ALDH6A1 gene, which encodes acylating methylmalonate-semialdehyde dehydrogenase. This enzyme converts 2-methyl-3-oxopropanoate, CoA and water into propanoyl-CoA, using NAD+ as an oxidizing agent, and producing a hydrogen ion and hydrogencarbonate as byproducts. Other forms of 3-hydroxyisobutyric aciduria may be caused by a mutation in the gene encoding 3-hydroxyisobutyrate dehydrogenase, which forms (S)-methylmalonic acid semialdehyde from (S)-3-hydroxyisobutyric acid. This mutation leads to an accumulation of (S)-3-hydroxyisobutyric acid, as no other processes in the pathway use it. 3-hydroxyisobutyric aciduria is characterized by elevated levels of 3-hydroxyisobutyric acid excreted in the urine. Symptoms of the disorder include dysmorphic features, developmental delays and intellectual disabilities. Treatments are not currently well researched due to the rarity of the condition, but protein-restricted diets may be helpful. It is estimated that 3-hydroxyisobutyric aciduria affects less than 1 in 1,000,000 people, with only 12 cases having been reported by 2006.

3-Hydroxyisobutyric acid dehydrogenase deficiency (3-hydroxyisobutyric aciduria) is an extremely rare inborn error of metabolism (IEM), potentially caused by numerous mechanisms. It is currently thought to be autosomal recessively inherited. At least two cases of 3-hydroxyisobutyric aciduria were determined to be caused by a mutation in the ALDH6A1 gene, which encodes acylating methylmalonate-semialdehyde dehydrogenase. This enzyme converts 2-methyl-3-oxopropanoate, CoA and water into propanoyl-CoA, using NAD+ as an oxidizing agent, and producing a hydrogen ion and hydrogencarbonate as byproducts. Other forms of 3-hydroxyisobutyric aciduria may be caused by a mutation in the gene encoding 3-hydroxyisobutyrate dehydrogenase, which forms (S)-methylmalonic acid semialdehyde from (S)-3-hydroxyisobutyric acid. This mutation leads to an accumulation of (S)-3-hydroxyisobutyric acid, as no other processes in the pathway use it. 3-hydroxyisobutyric aciduria is characterized by elevated levels of 3-hydroxyisobutyric acid excreted in the urine. Symptoms of the disorder include dysmorphic features, developmental delays and intellectual disabilities. Treatments are not currently well researched due to the rarity of the condition, but protein-restricted diets may be helpful. It is estimated that 3-hydroxyisobutyric aciduria affects less than 1 in 1,000,000 people, with only 12 cases having been reported by 2006.

3-Hydroxyisobutyric aciduria, also called HIBA, is an extremely rare inherited inborn error of metabolism (IEM) of valine metabolism. Only 12-13 patients have been identified with this condition. It is an autosomal recessive disorder that may be caused, in some cases, by a defective aldehyde dehydrogenase 6 family member A1 (ALDH6A1) gene which codes for methylmalonate semialdehyde dehydrogenase (MMSDH). MMSDH is a mitochondrial methylmalonate semialdehyde dehydrogenase that plays a role in the valine and pyrimidine catabolism. This protein catalyzes the irreversible oxidative decarboxylation of malonate and methylmalonate semialdehydes to acetyl- and propionyl-CoA. Another possible cause of the disorder is a mutation in 3-hydroxyisobutyrate dehydrogenase, a mitochondrial enzyme which catalyzes the conversion of 3-hydroxyisobutyrate into methylmalonic semialdehyde, or in the conversion of the semialdehyde to propionyl-CoA. Individuals with this disorder have very high levels of 3-hydroxyisobutyric acid secreted in their urine. Other indications of organic acidemia are also present. Signs and symptoms of 3-hydroxyisobutyric aciduria include developmental delay, dysmorphic facial features, and brain abnormalities. The excretion of 3-hydroxyisobutyric acid in the urine can range from 170 to 390 mmol/mol of creatinine. Concentrations of free carnitine are also low, and esterified carnitine can be elevated in patients. Protein-restricted diets and carnitine supplementation have been tried with varying degrees of success.