Gaucher's disease or Gaucher disease (GD) is a genetic disorder in which glucocerebroside accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase, which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages. Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.
Lysosomal storage diseases are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective due to a mutation, the large molecules accumulate within the cell, eventually killing it.
Niemann–Pick disease (NP), also known as acid sphingomyelinase deficiency, is a group of rare genetic diseases of varying severity. These are inherited metabolic disorders in which sphingomyelin accumulates in lysosomes in cells of many organs. NP types A, A/B, and B are caused by mutations in the SMPD1 gene, which causes a deficiency of an acid sphingomyelinase (ASM). NP type C is now considered a separate disease, as SMPD1 is not involved, and there is no deficiency in ASM.
Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine. It is a genetic disorder that follows an autosomal recessive inheritance pattern. It is a rare autosomal recessive disorder resulting from accumulation of free cystine in lysosomes, eventually leading to intracellular crystal formation throughout the body. Cystinosis is the most common cause of Fanconi syndrome in the pediatric age group. Fanconi syndrome occurs when the function of cells in renal tubules is impaired, leading to abnormal amounts of carbohydrates and amino acids in the urine, excessive urination, and low blood levels of potassium and phosphates.
Neuronal ceroid lipofuscinosis is a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These lipopigments are made up of fats and proteins. Their name comes from the word stem "lipo-", which is a variation on lipid, and from the term "pigment", used because the substances take on a greenish-yellow color when viewed under an ultraviolet light microscope. These lipofuscin materials build up in neuronal cells and many organs, including the liver, spleen, myocardium, and kidneys.
Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.
Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.
A lipid storage disorder is any one of a group of inherited metabolic disorders in which harmful amounts of fats or lipids accumulate in some body cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize and break down lipids or, they produce enzymes that do not work properly. Over time, the buildup of fats may cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen, and bone marrow.
Aceruloplasminemia is a rare autosomal recessive disorder in which the liver can not synthesize the protein ceruloplasmin properly, which is needed to transport copper around the blood. Copper deficiency in the brain results in neurological problems that generally appear in adulthood and worsen over time.
Heřmanský–Pudlák syndrome is an extremely rare autosomal recessive disorder which results in oculocutaneous albinism, bleeding problems due to a platelet abnormality, and storage of an abnormal fat-protein compound. It is thought to affect around 1 in 500,000 people worldwide, with a significantly higher occurrence in Puerto Ricans, with a prevalence of 1 in 1800. Many of the clinical research studies on the disease have been conducted in Puerto Rico.
The GM1 gangliosidoses, usually shortened to GM1, are gangliosidoses caused by mutation in the GLB1 gene resulting in a deficiency of beta-galactosidase. The deficiency causes abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells, resulting in progressive neurodegeneration. GM1 is a rare lysosomal storage disorder with a prevalence of 1 to every 100,000 to 200,000 live births worldwide, although rates are higher in some regions.
Infantile Refsum disease (IRD) is a rare autosomal recessive congenital peroxisomal biogenesis disorder within the Zellweger spectrum. These are disorders of the peroxisomes that are clinically similar to Zellweger syndrome and associated with mutations in the PEX family of genes. IRD is associated with deficient phytanic acid catabolism, as is adult Refsum disease, but they are different disorders that should not be confused.
Sialin, also known as H(+)/nitrate cotransporter and H(+)/sialic acid cotransporter, is a protein which in humans is encoded by the SLC17A5 gene.
Beta-mannosidosis, also called lysosomal beta-mannosidase deficiency, is a disorder of oligosaccharide metabolism caused by decreased activity of the enzyme beta-mannosidase. This enzyme is coded for by the gene MANBA, located at 4q22-25. Beta-mannosidosis is inherited in an autosomal recessive manner. Affected individuals appear normal at birth, and can have a variable clinical presentation. Infantile onset forms show severe neurodegeneration, while some children have intellectual disability. Hearing loss and angiokeratomas are common features of the disease.
Jansky–Bielschowsky disease is an extremely rare autosomal recessive genetic disorder that is part of the neuronal ceroid lipofuscinosis (NCL) family of neurodegenerative disorders. It is caused by the accumulation of lipopigments in the body due to a deficiency in tripeptidyl peptidase I as a result of a mutation in the TPP1 gene. Symptoms appear between ages 2 and 4 and consist of typical neurodegenerative complications: loss of muscle function (ataxia), drug resistant seizures (epilepsy), apraxia, development of muscle twitches (myoclonus), and vision impairment. This late-infantile form of the disease progresses rapidly once symptoms are onset and ends in death between age 8 and teens. The prevalence of Jansky–Bielschowsky disease is unknown; however, NCL collectively affects an estimated 1 in 100,000 individuals worldwide. Jansky–Bielschowsky disease is related to late-infantile Batten disease and LINCL, and is under the umbrella of neuronal ceroid lipofuscinosis.
Galactosialidosis, also known as neuraminidase deficiency with beta-galactosidase deficiency, is a genetic lysosomal storage disease. It is caused by a mutation in the CTSA gene which leads to a deficiency of enzymes β-galactosidase and neuraminidase. This deficiency inhibits the lysosomes of cells from functioning properly, resulting in the accumulation of toxic matter within the cell. Hallmark symptoms include abnormal spinal structure, vision problems, coarse facial features, hearing impairment, and intellectual disability. Because galactosialidosis involves the lysosomes of all cells, it can affect various areas of the body, including the brain, eyes, bones, and muscles. Depending on the patient's age at the onset of symptoms, the disease consists of three subtypes: early infantile, late infantile, and juvenile/adult. This condition is considered rare, with most cases having been in the juvenile/adult group of patients.
Schindler disease, also known as Kanzaki disease and alpha-N-acetylgalactosaminidase deficiency, is a rare disease found in humans. This lysosomal storage disorder is caused by a deficiency in the enzyme alpha-NAGA (alpha-N-acetylgalactosaminidase), attributable to mutations in the NAGA gene on chromosome 22, which leads to excessive lysosomal accumulation of glycoproteins. A deficiency of the alpha-NAGA enzyme leads to an accumulation of glycosphingolipids throughout the body. This accumulation of sugars gives rise to the clinical features associated with this disorder. Schindler disease is an autosomal recessive disorder, meaning that one must inherit an abnormal allele from both parents in order to have the disease.
Infantile free sialic acid storage disease (ISSD) is a lysosomal storage disease. ISSD occurs when sialic acid is unable to be transported out of the lysosomal membrane and instead accumulates in the tissue, causing free sialic acid to be excreted in the urine. Mutations in the SLC17A5 gene cause all forms of sialic acid storage disease. The SLC17A5 gene is located on the long (q) arm of chromosome 6 between positions 14 and 15. This gene provides instructions for producing a protein called sialin that is located mainly on the membranes of lysosomes, compartments in the cell that digest and recycle materials.
X-linked spinal muscular atrophy type 2, also known as arthrogryposis multiplex congenita X-linked type 1 (AMCX1), is a rare neurological disorder involving death of motor neurons in the anterior horn of spinal cord resulting in generalised muscle wasting (atrophy). The disease is caused by a mutation in UBA1 gene and is passed in an X-linked recessive manner by carrier mothers to affected sons.
Lysosomal acid lipase deficiency or Wolman Disease, is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. This enzyme plays an important role in breaking down fatty material in the body. Infants, children and adults that have LAL deficiency experience a range of serious health problems. The lack of the LAL enzyme can lead to a build-up of fatty material in several body organs including the liver, spleen, gut, in the wall of blood vessels and other important organs.
