Browsing Pathways

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.

Krabbe disease, also called globoid cell leukodystrophy, is an extremely rare inherited inborn error of metabolism (IEM). It is a degenerative disorder that affects the nervous system. It has an estimated prevalence of 1/100,000 in the Northern European population and a worldwide incidence of 1/100,000-1/250,000 live births. Krabbe disease is an autosomal recessive disorder that is caused by a deficiency of an enzyme called galactosylceramidase. Galactosylceramidase is a lysosomal protein that hydrolyzes the galactose ester bonds of ceramides and ceramide derivatives including galactocerebroside, galactosylsphingosine (psychosine), lactosylceramide, and monogalactosyldiglyceride. More specifically, galactosylceramidase is an enzyme that is involved in the catabolism (via the removal of galactose) of galactosylceramide, a major lipid in myelin, kidney, and epithelial cells of the small intestine and colon. Defects in galactosylceramidase lead to the accumulation of cytotoxic psychosine, which ultimately leads to apoptosis of oligodendrocytes and demyelination. As a result, this enzyme deficiency impairs the growth and maintenance of myelin, the protective sheath around nerve cell axons that ensures that electrical impulses are rapidly transmitted. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). Krabbe disease is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that often have multiple nuclei. There are three different phenotypes for Krabbe disease: infantile, juvenile, and late-onset. Neurodegeneration and early death (at age 2-3) occur in most infantile cases. In juvenile patients, the disease is often fatal 2-7 years after the symptoms begin. Adult-onset patients can survive many years after symptoms first manifest. The symptoms of infantile Krabbe disease usually begin during the first year of life. Typically, the initial signs and symptoms include feeding difficulties, episodes of fever without any sign of infection, irritability, stiff posture, muscle weakness, and slowed mental and physical development. Muscles continue to weaken as the disease progresses which decreases the infant's ability to move, chew, swallow, and breathe. It is also common for affected infants to experience vision loss and seizures. Treatment is limited to hematopoietic stem cell transplantation in pre-symptomatic infantile patients and mildly affected late-onset patients. Stem cell transplants have been shown to slow the progression of the disease.

Arginine:glycine amidinotransferase deficiency, also called AGAT deficiency, is an extremely rare inherited inborn error of metabolism (IEM) and an autosomal recessive disorder caused by a defective arginine:glycine amidinotransferase (AGAT) gene. It manifests as a creatine deficiency disorder. Only 14 individuals with AGAT deficiency have been reported. The AGAT enzyme catalyzes the transfer of an amidino group from arginine to glycine yielding ornithine and guanidinoacetate, which is the immediate precursor of creatine. Deficiencies in the AGAT enzyme, therefore, lead to low levels of ornithine, guanidinoacetate, and creatine. People with AGAT deficiency have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviours that affect communication and social interaction. Individuals with AGAT deficiency may experience seizures, especially when they have a fever. Children with AGAT deficiency may not gain weight and grow at the expected rate (failure to thrive) and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily due to their low creatine levels. The treatment for AGAT deficiency is creatine supplementation since the body cannot make the creatine on its own. Early-stage (fetal and early postnatal) creatine treatment has shown that those affected can develop normally and that early diagnosis and treatment can substantially improve the final prognosis of AGAT deficiency.

Arginine:glycine amidinotransferase deficiency, also called AGAT deficiency, is an extremely rare inherited inborn error of metabolism (IEM) and an autosomal recessive disorder caused by a defective arginine:glycine amidinotransferase (AGAT) gene. It manifests as a creatine deficiency disorder. Only 14 individuals with AGAT deficiency have been reported. The AGAT enzyme catalyzes the transfer of an amidino group from arginine to glycine yielding ornithine and guanidinoacetate, which is the immediate precursor of creatine. Deficiencies in the AGAT enzyme, therefore, lead to low levels of ornithine, guanidinoacetate, and creatine. People with AGAT deficiency have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviours that affect communication and social interaction. Individuals with AGAT deficiency may experience seizures, especially when they have a fever. Children with AGAT deficiency may not gain weight and grow at the expected rate (failure to thrive) and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily due to their low creatine levels. The treatment for AGAT deficiency is creatine supplementation since the body cannot make the creatine on its own. Early-stage (fetal and early postnatal) creatine treatment has shown that those affected can develop normally and that early diagnosis and treatment can substantially improve the final prognosis of AGAT deficiency.

Increased lactic acid concentrations in urine or serum can be a result of many metabolic disorders but also of other origin (infections, etc.). Respiratory chain defects account for most of the metabolic causes of lactic acid accumulation. Often alanine is also high. A urine spectrum indicating an increased lactic acid and alanine concentration is shown.

Increased lactic acid concentrations in urine or serum can be a result of many metabolic disorders but also of other origin (infections, etc.). Respiratory chain defects account for most of the metabolic causes of lactic acid accumulation. Often alanine is also high. A urine spectrum indicating an increased lactic acid and alanine concentration is shown.

Lactose intolerance is a condition in which the body does not support the ingestion of lactose through the consumption of milk, cheese, and other dairy products. This intolerance occurs due to the lack of the enzyme intestinal lactase, which is an enzyme found in newborns. The frequency of this enzyme declines rapidly after the child stops breastfeeding. Lactase deficiency is most prevalent in Asia, Africa and Indigenous populations in North and South America. The symptoms of lactose intolerance include diarrhea, bloating, abdominal pain and excessive flatus. The cause of these symptoms is the processing of the ingested lactose being fermented by intestinal bacteria instead of in the small intestine, where lactose is meant to be processed.

Lactose intolerance is a condition in which the body does not support the ingestion of lactose through the consumption of milk, cheese, and other dairy products. This intolerance occurs due to the lack of the enzyme intestinal lactase, which is an enzyme found in newborns. The frequency of this enzyme declines rapidly after the child stops breastfeeding. Lactase deficiency is most prevalent in Asia, Africa and Indigenous populations in North and South America. The symptoms of lactose intolerance include diarrhea, bloating, abdominal pain and excessive flatus. The cause of these symptoms is the processing of the ingested lactose being fermented by intestinal bacteria instead of in the small intestine, where lactose is meant to be processed.

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.

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.