Browsing Pathways

Glycogen storage disease type III, which is also known as GSD III or Cori disease, is a rare inherited inborn error of metabolism (IEM). GSD-III has an incidence of about 1 in 100 000. The incidence of GSD-III is higher in North African Jews (1 in 5 400), Faroese (1 in 3 100) and the Inuit population in Nunavik, Canada (1 in 2 500). GSDIII is an autosomal recessive metabolic disorder characterized a deficiency in glycogen debranching enzymes, specifically the enzyme amylo-1,6 glucosidase. GSD III causes a buildup of a complex sugar called glycogen in the body's cells. The accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles. GSD III typically presents during infancy with hypoglycemia and failure to thrive. Clinical examination usually reveals hepatomegaly. Muscular disease, including hypotonia and cardiomyopathy, usually occurs later in life. GSD III is divided into the types IIIa, IIIb, IIIc, and IIId, which are distinguished by their pattern of signs and symptoms. GSD types IIIa and IIIc affect primarily the liver and muscles. This is in direct contrast to GSD types IIIb and IIId which affect only the liver. Differentiating between the types of GSD III which affect the same tissue is extremely challenging. Out of all the GSD types, IIIa and IIIb are the condition's most common forms. Treatment for glycogen storage disease type III may involve a high-protein diet, in order to facilitate gluconeogenesis.

Glycogen storage disease type IV, also called GSD IV, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective 1,4-alpha-glucan-branching enzyme. 1,4-alpha-glucan-branching enzyme catalyzes the conversion of amylose into glycogen which is essential component for cells to build up bodies. Symptoms of the disorder happen mainly in infants, which include failure to thrive, loss weight, enlarged liver and spleen, etc. Treatment with strict dietary therapy is effective in some cases. It is estimated that GSD IV affects 1 in 600,000 to 800,000 individuals worldwide.

Glycogen storage disease type VI, also called GSDVI or Hers disease, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective liver glycogen phosphorylase. Liver glycogen phosphorylase catalyzes the conversion of glycogen into amylose which is substrate of 1,4-alpha-glucan-branching enzyme and glycogen debranching enzyme. The disorder may show as enlarged liver in infancy to early childhood. Treatment may not required for some individuals. Glycogen storage disease type VI has been reported in approximately 11 people at least.

Mucopolysaccharidosis type VII (MPS VII), also called Sly syndrome, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by mutations in the GUSB gene. This gene encodes for the beta-glucuronidase enzyme, which normally breaks down glycosaminoglycans (GAGs). However, without beta-glucuronidase, accumulation of GAGs in cells specifically the lysosome increases. The increase in cell size causes tissues and organs to become enlarged as well. This disorder is characterized by macrocephaly, a buildup of fluid in the brain, characteristic facial features, and a large tongue. Other symptoms may include hepatosplenomegaly, heart valve abnormalities, and umbilical or inguinal hernias. MPS VII also causes various skeletal abnormalities, including joint issues and decreased growth. Treatments such as enzyme replacement therapy are still fairly new, however traditionally treatments for Mucopolysaccharidosis VII included symptom relief such as surgery. It is estimated that MPS VII affects 1 in 250,000 individuals.  

Congenital sucrase-isomaltase deficiency is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by mutatins in the SI gene which encodes for the enzyme sucrase-isomaltase. Sucrase-isomaltase catalyzes the breakdown of sucrose, maltose and larger carbohydrates. Sucrose and maltose are disaccharides, and are broken down into simple sugars during digestion. Sucrose is broken down into glucose and fructose, while maltose is broken down into two glucose molecules. This disorder is characterized by stomach cramps, bloating, excess gas production, and diarrhea after ingestion of sucrose and maltose. These digestive problems can lead to failure to thrive and malnutrition. There is no cure for Sucrase-Isomaltase Deficiency, however orally administrated Sacrosidase can help relieve symptoms. Similarly, restricting high sugar diets can also help. Most affected children are better able to tolerate sucrose and maltose as they get older. Frequency of Sucrase-Isomaltase Deficiency is about 1 in 5,000 with European descent. 

Primary hyperolaria type 2 (PH2) is a rare condition resulting from glyoxylate reductase/hydroxypyruvate reductase (GR/HPR) enzyme deficiency. PH2 results in calcium oxalate (also known as oxalic acid) deposits and end-stage renal disease. These deposits may cause kidney damage or failure.

Pyruvate kinase deficiency is a genetic disorder. It affects red blood cells in the body. Patients are affected by a condition called chronic hemolytic anemia, which is where red blood cells undergo hemolysis before they are meant to which causes anemia in the patient. Symptoms of this condition can include jaundice, fatigue, dyspnea and splenomegaly. Gallstones are also common to patients with this disorder. This disorder is diagnosed through genetic testing. In mild cases, no treatment is required. Patients with more severe cases may require blood transfusions, and occasionally the spleen is removed to aid with the reduction of red blood cell destruction.

Phosphoenolpyruvate Carboxykinase Deficiency 1 (PEPCK1), also called Phosphoenolpyruvate carboxykinase-1 (PCK1) deficiency, Phosphopyruvate carboxylase deficiency, Phosphoenolpyruvate carboxylase deficiency, Phosphoenolpyruvate carboxykinase deficiency, or PEP carboxykinase deficiency, is a rare inborn error of metabolism (IEM) and an autosomal recessive disorder of gluconeogenesis caused by a deficient PEPCK1 enzyme. PEPCK1 catalyzes the conversion of amino acids into sugars, mainly glucose, which is important in preventing hypoglycemia. This disorder is characterized by a large accumulation of lactic acid in the blood. Symptoms of the disorder include hepatomegaly, failure to thrive and liver failure, depending on the severity of the case. Treatment including heavy carbohydrates and fasting is very effective. It is estimated that Phosphoenolpyruvate Carboxykinase Deficiency 1 has only affected 10 individuals around the world according to medical literature.

Fructosuria, full name essential fructosuria, is a condition that presents no symptoms and is benign. Patients with this condition exhibit a mutation in the KHK gene, which leads to fructose metabolism not being completed. This is because of a lack of the enzyme fructokinase, found in the liver. It is identified by the presence of fructose in the urine, which in people without the condition should not be present.

Fructose-1,6-bisphosphatase deficiency (FBP1D) is an autosomal recessive inborn error of metabolism (IEM) caused by a mutation in the FBP1 gene which encodes for fructose-1,6-bisphosphatase-1. This enzyme is responsible for catalyzing the conversion of fructose 1,6-bisophosphate into fructose 5-phosphate by removing a phosphate group from it as part of the gluconeogenesis pathway. FBP1D is characterized by hypoglycemia and acidosis after fasting, caused by the impairment of gluconeogenesis. Symptoms can also include hyperventilation. Treatment includes feeding more often with foods enriched with glucose, as well as avoiding foods high in fructose and sucrose, as well as avoiding fasting for longer than overnight. It is estimated that FBP1D affects between 1 in 350,000 and 1 in 900,000 individuals.