Browsing Pathways

Glycogenosis, Type IB, also called von Gierke disease or GSDI, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder which caused by a defective glucose-6-phosphate translocase. Glucose-6-phosphate translocase transports glucose 6-phosphate from endoplasmic reticulum (ER) to cell, which glucose 6-phosphate is required for various pathways as the substrate. This disorder damages the ability of converting glycogen into glucose. Symptoms of the disorder include longer sleeping time through night, tiredness and seizures due to low blood sugar. Treatment with diet management is very effective.

Glycogenosis, Type IC, a sub-category of glycogen storage disease type I, is a rare inborn error of metabolism (IEM) and caused by a defective glucose-6-phosphatase translocase. Glucose-6-phosphate translocase transports glucose 6-phosphate from endoplasmic reticulum (ER) to cell, which glucose 6-phosphate is required for various pathways as the substrate. This disorder damages the ability of converting glycogen into glucose. Symptoms of the disorder include longer sleeping time through night, tiredness and seizures due to low blood sugar. Treatment with diet management is very effective. Currently, only few cases have been reported.

11-beta-Hydroxylase Deficiency, also called congenital adrenal hyperplasia (CAH), is an autosomal recessive disorder and caused by a defective 11-beta-hydroxylase. 11-beta-hydroxylase catalyzes the conversion of cortexolone into cortisol which is useful for maintaining blood sugar levels and suppressing inflammation. This disorder is characterized by a large accumulation of cortexolone in the endoplasmic reticulum (ER). Symptoms of the disorder include abnormality of hair growth rate and menstrual cycle. It is estimated that 11-beta-hydroxylase deficiency affects 1 in 100,000 to 200,000 newborns.

Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the steps of biosynthesis of cortisol from cholesterol in the adrenal glands, also known as steroidogenesis. 21-hydroxylase deficiency, also known as CYP21 deficiency or CAH1, is an autosomal recessive disorder that accounts for the vast majority of cases of CAH. This deficiency affects cells in the adrenal cortex of the adrenal glands, and due to the deficiency in an enzyme used in many pathways. This prevents the completion of several hormone biosynthesis pathways, including those producing aldosterone and cortisol, and leads to a buildup of their precursors, including 17a-hydroxypregnenolone, which are then processed by the pathways that produce androgen hormones including testosterone. This disorder can vary in severity, depending on the amount of functional enzyme present. The most severe form is known as the salt-wasting form of 21-hydroxylase, and is caused by a complete lack of functional enzyme. This form is called the salt-wasting form, as the lack of aldosterone produced leads to high levels of sodium excreted in the urine, causing infant blood volume to decrease. High potassium levels in blood are also often observed, but if properly diagnosed, saline solution and hydrocortisone can restore normal blood levels and sodium content. In addition, males are typically visually unaffected, but females often possess ambiguous genitalia due to the excess exposure to testosterone during development. The second most severe form is known as the simple virilising form, which does not involve the salt loss of the salt-wasting form, due to a partially functional 21-hydroxylase enzyme. However, the androgen hormones build up similarly, leading to females with some amount of virilisation, or some amount of male characteristics, including ambiguous genitalia. The third and least severe form, known as the non-classical or late onset form, has the highest function in 21-hydroxylase enzymes, and leads to the smallest buildup of androgen hormones. This means that females exhibit little to no virilisation at birth, but as they age can experience male-associated hair growth and baldness, as well as decreased fertility and menstruation irregularities. It can also lead to an early puberty in both males and females, though treatment can help prevent this if it is caught in time.

Corticosterone methyloxidase type I (CMO-I) deficiency, also known as 18-hydroxylase deficiency or aldosterone deficiency among other names, is a genetic disorder that is autosomally linked and caused by a defective CYP11B2 gene. This gene encodes the cytochrome P450 11B2 mitochondrial protein, also called aldosterone synthase, which is used to catalyze the conversion of 18-hydroxycorticosterone to aldosterone. This leads to a decrease in the amount of aldosterone present in the cells, which is responsible for an increased amount of salt excreted in the urine, known as salt wasting. In CMO-I deficiency, aldosterone levels are so low that they are undetectable in plasma.

Corticosterone methyloxidase type II (CMO-II) deficiency, also called 18-oxidase defiency or aldosterone deficiency II among other names, is a genetic disorder that is autosomally linked. It is caused by a mutation in the cytochrome P450 11B2 gene, whose protein product is responsible for the formation of aldosterone from 18-hydroxycorticosterone (18-OHB), as well as converting progesterone to 11b-hydroxyprogesterone. The conversion of 18-OHB to aldosterone is the only reaction that uses 18-OHB, and due to the enzyme not being entirely functional, it builds up in the cell, while aldosterone levels will be lowered. However, since progesterone and 11b-hydroxyprogesterone are both produced and used by other reactions, their levels in the cell are not changed as drastically. Compared to the CMO-I deficiency, the CMO-II deficiency has less severe mutations in the gene, which cause it to have less severe changes in aldosterone and 18-OHB concentrations. The CMO-II deficiency, and its resulting aldosterone deficiency can cause a salt-wasting phenotype in children, due to aldosterone being responsible for the resorption of sodium in the body, as well as secretion of potassium. With levels of aldosterone being lower due to this deficiency, excess sodium is excreted in the urine, and higher than average levels of potassium in the serum. Aside salt-wasting and potential failure to thrive as an infant due to this, there are no symptoms, such as genital abnormalities, that are seen in similar salt-wasting disorders like CYP21 deficiency.

The congenital disorder of glycosylation type IID, also called CDG IId or CDG2D is a recessive genetic disorder caused by an autosomal mutation in the B4GALT1 gene which encodes the protein beta-1,4-galactosyltrasnferase 1. This protein is responsible for the conversion of D-glucose and uridine diphosphategalactose to alpha-lactose and uridine 5’-diphosphate. This reaction occurs in the mammary glands during lactation, and may be present during oligosaccharide synthesis in glycoproteins. This is a type II disorder, which means that the glycosylation steps affected are trimming, elongation and processing of glycans, whereas in type I disorders, the steps that are disrupted are assembly of oligosaccharides and their transfer. CDG disorders are characterized by mental and motor retardation, as well as increased levels of transferrins in the serum.

GLUT1 deficiency syndrome, also called GLUT1-DS or De Vivo disease, is an autosomal dominant disorder and caused by a defective solute carrier family 2, facilitated glucose transporter member 1. Solute carrier family 2, facilitated glucose transporter member 1 transport D-glucose from cell into Golgi apparatus which D-glucose is substrate of lactose synthase. This disorder is characterized by dissipation of D-glucose in both Golgi apparatus and cell cytoplasm. Symptoms of the disorder include developmental delays of mental and motor. There is no cure for GLUT1 deficiency syndrome currently; but diet management can help control symptoms. It is estimated that 500 cases have been reported.

Glycogenosis, Type IA, also called Von Gierke Disease, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder and caused by a defective glucose-6-phosphatase. Glucose-6-phosphatase catalyzes the conversion of glucose 6-phosphate into D-glucose and conversion of D-glucose to glucose 6-phosphate. Symptoms of the disorder include hypoglycemic seizures, lactic acidosis, hyperuricemia, etc. Treatment with diet management is very effective.

Joubert syndrome is a condition in which brain development is not completed as it should be, including the lack or underdevelopment of the part of the brain that regulates balance and coordination and an abnormal brain stem. The symptoms affect a variety of body parts in the patient, including apnea, ataxia brought on by hypotonia, abnormal eye movements and intellectual disability. Many different gene mutations are responsible for Joubert syndrome, all of the proteins created from these genes affecting the cilia that are found on the cell surface. It can be confirmed through its hallmark molar tooth imprint that shows up on brain scans of the patient, a visualization of the malformed brain stem and cerebellar vermis.