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.

Canavan Disease (Canavan-Van Bogaert-Bertrand Disease; Aminoacylase 2 Deficiency; Spongy Degeneration of the Central Nervous System; Aspartoacylase Deficiency; ASP Deficiency; ACY2 Deficiency; ASPA) is a rare autosomal recessive disease caused by a defect in the ASPA gene which codes for aspartoacylase. A deficiency in this enzyme results in accumulation of N-Acetyl-L-aspartic acid in plasma, spinal fluid, and urine. Symptoms, which present at birth, include myclonus, irritability, hypotonia, motor retardation, and poor head control. The neurological complications are due to demyelination of neurons and leukodystrophy. Premature death often results, though lithium citrate can be used as a treatment.

CCarbamoyl 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.

Cerebrotendinous Xanthomatosis, also called CTX, is a rare inborn error of metabolism (IEM) which results from a genetic mutation. More specifically, it is the result of a mutated CYP27A1 gene. This said gene is responsible for encoding sterol 27-hydroxylase. The importance of this enzyme if the following, the said enzyme is responsible for the catalysis during the oxidation of several compounds. In particular, the said enzyme interacts with sterol intermediates, and 7-alpha,12-alpha-triol, among others. CTX is rare and can be thought of as an inherited lipid-storage disease. It causes the widespread deposition of two main compounds (cholesterol and cholestanol) throughout essentially every single tissue in the body. Including, the brain and lungs, to the detriment of the affected. Symptoms of CTX are neurological dysfunction, premature atherosclerosis, and cataracts.

CHILD Syndrome, (Congenital Hemidysplasia with Icthyosiform Erythroderma and Limb Defects; Ichthyosiform Eruthroderma, Unilateral, with Epsilateral Malformations, Especially Absence Deformity of Limbs) is caused by a mutation in the gene encoding NADH steroid dehydrogenase-like protein (NSDHL). A defect in sterol-4 alpha-carboxylate 3-dehydrogenase, which normally catalyzes the reaction 3-beta-hydroxy-4-beta-methyl-5-alpha-cholest-7-ene-4-alpha-carboxylate + NAD+ = 4-alpha-methyl-5-alpha-cholest-7-en-3-one + CO2 + NADH, causes accumulation of 8(9)cholestenol and 8-dehydrocholesterol in plasma. Symptoms of CHILD syndrome include hearing defects, hemidysplasia, unilateral hypomelia, ichthyosiform nevi, limb abnormalities, lung hypoplasia, and punctate calcifications.

Chondrodysplasia Punctata 2, X Linked Dominant (CDPX2; CPDXD; CPXD; Conradi-Hunermann Syndrome; Happle Syndrome; Conradi-Hunermann-Happle Syndrome is caused by a mutation in the gene encoding delta(8)-delta(7) sterol isomerase emopamil-binding protein (EBP). EBP contains the code for the enzyme 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase, which normally catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers. A defect in this enzyme causes accumulation of 8-dehydrocholesterol and 8(9)cholestenol in the plasma. Symptoms include alopecia, dysmorphism, hyperkeratosis, ichthyosis, kyphoscoliosis, limb abnormalities and deformities, and mental retardation.

Citrullinemia Type 1, also called argininosuccinate synthetase deficiency, argininosuccinic acid synthetase deficiency or ASS deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the urea cycle caused by a deficiency of argininosuccinate synthetase. Argininosuccinate synthetase is an important enzyme in the process of removing nitrogen from the body. This disorder is characterized by a large accumulation of ammonia in the blood as well as other bodily fluids . Symptoms of the disorder include vomiting, lethargy and intracranial pressure. Treatment with protein restriction and intravenous administration of arginine can help manage symptoms, and diet management throughout the patient’s life can also show improvement. It is estimated that citrullinemia type 1 affects 1 in 57,000 individuals.

Congenital Bile Acid Synthesis Defect Type II is a congenital defect in bile acid synthesis with delta(4)-3-oxosteroid 5-beta-reductase deficiency is caused by mutation in the AKR1D1 gene. 3-oxo-5-beta-steroid 4-dehydrogenase catalyzes the bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one. Chenodeoxycholic acid and cholic acid are decreased in plasma and urine. Symptoms of this disease include cholestatic jaundice, atypical oxo and allo bile acids in urine and serum, liver failure, and steatosis.

Congenital Bile Acid Synthesis Defect Type III (CBASIII) is caused by a defect in 25-hydroxycholesterol 7-alpha-hydroxylase, which plays a role in synthesis of bile acids. The synthesis of primary bile acids from cholesterol occurs via two pathways: the classic neutral pathway involving cholesterol 7-alpha-hydroxylase (CYP7A1), and the acidic pathway involving a distinct microsomal oxysterol 7-alpha-hydroxylase (CYP7B1). CBASIII is characterized by accumulation of bile acids in the urine. Symptoms include severe cholestasis, cirrhosis, and liver failure.

Congenital Erythropoietic Porphyria (CEP), also known as Gunther Disease, uroporphyrinogen III synthase defiency or UROS deficiency, is a rare autosomal recessive rare inborn error of metabolism (IEM). It is a disorder of the porphyrin metabolism pathway caused by a mutation in the UROS gene which encodes for uroporphyrinogen-III synthase. This enzyme catalyzes the dehydrogenation of hydroxymethylbilane into water and uroporphyrinogen III, which will undergo several more reactions to eventually form heme. This disorder is characterized by a large accumulation of porphyrins in the feces, urine and plasma, as well as in bones and teeth, potentially giving them a darkened or red appearance. Symptoms of this disorder include sensitivity to light, leading to potential skin damage as children, which can then lead to severe deformities. Red urine and teeth can also be seen in infancy. Treatment of CEP includes limiting or eliminating exposure to the sun, blood transfusions, and potentially bone marrow transplants or stem cell treatment. It is estimated that CEP affects less than 1 in 1,000,000 individuals.