Question 1

Tay-Sachs (HEXA)

Accepted Answer

Tay-Sachs disease is caused by mutations in the HEXA gene, which encodes for one subunit of the enzyme beta-hexosaminidase A. The enzyme breaks down the toxic substance GM2 ganglioside in the brain and spinal cord. Symptoms usually develop from three months onwards, including loss of motor skills, increasing weakness, and strong startle response. Loss of vision and hearing, seizures, and paralysis normally follow. Life expectancy is 2 to 4 years. Very rare related diseases, which begin later in childhood, adolescence, or early adulthood are also known, but the symptoms are usually much milder. Tay-Sachs is rare in the general population, but tends to be concentrated in various ethnic groups. Among those of Ashkenazi Jewish descent, about 1 in 30 are carriers for the disease. There is also a high level of carriers in the Acadian (Cajun) population of Louisiana, and among French Canadians. However, extensive genetic counseling has led to a large reduction in the number of live births over recent decades. The faulty gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.
Sources
Kaback, M.M. & Desnick, R.J. (1999), “Hexosaminidase A Deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1218/
NIH, Genetics Home Reference: HEXA gene.
See http://ghr.nlm.nih.gov/gene/HEXA
NIH, Genetics Home Reference: Tay-Sachs Disease.
See http://ghr.nlm.nih.gov/condition/tay-sachs-disease
Recombine Website. Tay-Sachs Disease.
See https://recombine.com/diseases/taysachs-disease

Question 2

Canavan Disease (ASPA) ures in my FAQ?

Accepted Answer

Canavan disease is a disease affecting the brain, caused by defects in the ASPA gene. The gene encodes for the enzyme aspartoacylase, whose function is to decompose excess N-acetyl-L-aspartic acid (NAA) in the brain. If the enzyme fails to function, excess NAA interferes with the development of the myelin sheath, the insulating covering around axons which functions to increase speed of neural transmission. The most common form of Canavan Disease, the neonatal or infantile form, causes a failure to develop normal motor skills. They suffer from macrocephaly, hypotonia, and often irritability. Seizures and difficulty swallowing may occur. Children rarely survive beyond their teens, and many die earlier. A milder form of the disease, the juvenile form, sometimes occurs. This is associated with slower than normal development of speech and motor skills, but does not normally lead to severe symptoms or a shortened lifespan. Canavan disease is most common in those of Ashkenazi Jewish descent, where it is estimated to occur in 1 in 6,400 to 1 in 13,500 births. The incidence in the general population is much lower, but accurate estimates are not available. The disease is inherited as autosomal recessive, which typically requires both parents to be carriers of the faulty gene, most likely asymptomatically.
Sources
Matalon, R. & Michals-Matalon, K. (1999), “Canavan Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1234/
NIH, Genetics Home Reference: ASPA gene.
See http://ghr.nlm.nih.gov/gene/ASPA
NIH, Genetics Home Reference: Canavan disease.
See http://ghr.nlm.nih.gov/condition/canavan-disease

Question 3

Sickle Cell Disease (HBB)

Accepted Answer

Sickle cell disease is caused by mutations in the HBB gene, which encodes for the protein beta-globin, a component of hemoglobin. The main form of the disease is sickle cell anemia, where the red blood cells are bent into a sickle shape. Sickle cells break down more quickly than normal cells, often resulting in anemia. The irregular cell shape tends to block blood vessels, which can lead to pain and ischemia of organs, including strokes. Jaundice and damage to the spleen often occur. In some cases, pulmonary hypertension can occur and lead to heart failure. Other than sickle cell formation, other abnormal forms of hemoglobin can form. The various symptoms of sickle cell anemia shorten live expectancy to about 40 to 60 years. Sickle cell disease tends to be concentrated in particular ethnic groups. About 1 in 500 African Americans have sickle cell disease, while the figure is about 1 in 1,000 to 1 in 1,400 for Hispanic Americans. In all about 100,000 Americans suffer from sickle cell disease. As the population of the USA is around 321 million, this means that about 1 in 3210 Americans has the disease, making it the most common inherited blood disease. The faulty gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.
Sources
 Bender M.A. & Seibel, G.D. (2003), “Sickle Cell Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1377/
NIH, Genetics Home Reference: HBB gene.
See http://ghr.nlm.nih.gov/gene/HBB
NIH, Genetics Home Reference: Sickle Cell Disease.
See http://ghr.nlm.nih.gov/condition/sickle-cell-disease
Recombine Website. Sickle Cell Anemia.
See https://recombine.com/diseases/sickle-cell-anemia
US Census Bureau http://www.census.gov/popclock/

Question 4

Gaucher Disease (GBA)

Accepted Answer

Gaucher Disease is caused by mutations in the GBA gene. This gene encodes for the enzyme beta-glucocerebrosidase, which breaks down the substance glucocerebroside. The buildup of glucocerebroside causes damage to various organs. There are various types of Gaucher disease. Type 1 is the most common, and involves anemia, lung disease, enlargement of the spleen and liver, easy bruising of the skin, and skeletal disorders such as arthritis and high risk of fractures. The nervous system is not affected in type 1 Gaucher disease. Types 2 and 3 involve serious damage to the nervous system, with type 2 being the more aggressive, leading normally to early mortality. A perinatal form of the disease is also known, leading to prompt death after birth. Finally, a cardiovascular form of the disease mainly involves damage to the heart valves. In the general population, Gaucher disease is found in 1 in 60,000 to 1 in 80,000 new births. It is much more prevalent in various ethnic groups. Among those of Ashkenazi Jewish descent, the disease is found in 1 in 855 people (nearly all Type 1), with around 1 in 18 people being carriers. The disease is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.
Sources
Pastores, G.M. & Hughes, D.A. (2000), “Gaucher Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1269/
NIH, Genetic Home Reference: GBA gene.
See http://ghr.nlm.nih.gov/gene/GBA
NIH, Genetics Home Reference: Gaucher.
See http://ghr.nlm.nih.gov/condition/gaucher-disease
Recombine Website. Gaucher Disease.
See https://recombine.com/diseases/gaucher-disease

Question 5

Phenylketonuria (PAH)

Accepted Answer

Phenylketonuria (PKU) is caused by mutations in the PAH gene. This gene encodes for the enzyme phenylalanine hydroxylase, which breaks down the amino acid phenylalanine. The buildup of phenylalanine causes damage to the body, affecting mainly the brain. If left untreated, those with phenylketonuria suffer from intellectual disability, seizures, delayed development, and psychiatric problems. A musty odor from phenylalanine may be evident. Treatment is by a special low phenylalanine diet, which can allow for normal development if strictly adhered to. There are rarer, less damaging forms of the disease, known as non-PKU hyperphenylalaninemia. Phenylketonuria is found in 1 in 10,000 to 1 in 15,000 new births. Since screening and prompt treatment are almost universal in the USA, the symptoms are very rarely seen. The disease is more common in some ethnic groups, such as Turks (1 in 2,600 births) and Irish (1 in 4,600 births). The condition follows an autosomal recessive pattern, typically requiring both parents to be carriers asymptomatically.
Sources
Mitchell, J.J. (2000), “Phenylalanine hydroxylase deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1504/
NIH, Genetic Home Reference: PAH gene.
See http://ghr.nlm.nih.gov/gene/PAH
NIH, Genetics Home Reference: Phenylketonuria.
See http://ghr.nlm.nih.gov/condition/phenylketonuria
Recombine Website. Phenylalanine Hydroxylase Deficiency.
See https://recombine.com/diseases/phenylalanine-hydroxylase-deficiency

Question 6

Glycogen Storage Disease II (GAA)

Accepted Answer

Glycogen storage disease II, also known as Pompe disease, is caused by mutations in the GAA gene. This gene encodes for the enzyme alpha-glucosidase, which breaks down glycogen into glucose. Without this enzyme, glycogen can build up to toxic levels, damaging muscles, including the heart muscles, as well as an inability to maintain normal fasting glucose levels. The classic form of the disease emerges in the first few months of life. Babies exhibit muscle weakness, breathing difficulties, heart problems, and fail to thrive. Mortality rates are high, few surviving the first year without treatment. A “non-classic” infantile form appears in the first year of life. Symptoms are similar, but the heart tends to be less severely affected. Even so, breathing difficulties mean that few survive for more than a few years without treatment. A late-onset form of the disease is also known, in which symptoms first appear during late childhood, adolescence, or adulthood. Here muscle weakness and respiratory problems arise, but usually the heart is unaffected. Most sufferers from this form die within 30 years of diagnosis without treatment. Enzyme replacement therapy, along with treatment for the various symptoms, can extend survival to some extent. The incidence of glycogen storage disease type II is around 1 in 40,000 in the USA, rising to 1 in 14,000 among African Americans. The carrier rate reaches about 1 in 60 in the latter population. The defective genes are inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers for the faulty gene.
Sources
Leslie, N. & Tinkle, B.T. (2007), “Glycogen Storage Disease Type II (Pompe Disease),” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1261/
NIH, Genetics Home Reference: GAA gene.
See http://ghr.nlm.nih.gov/gene/GAA
NIH, Genetics Home Reference: Pompe Disease.
See http://ghr.nlm.nih.gov/condition/pompe-disease
Recombine Website: Glycogen Storage Disease, Type 2.
See https://recombine.com/diseases/glycogen-storage-disease-type-ii

Question 7

Question 8

Alpha Thalassemia (HBA1 / HBA2)

Accepted Answer

Alpha Thalassemia is caused by defects in the HBA1 or HBA2 genes. These genes encode for the protein alpha-globin, a component of hemoglobin. There are two forms of the disease: Hb Bart syndrome and HbH disease. The former is more severe, affecting unborn babies. They suffer from general edema (swelling from fluid buildup), anemia, heart defects, and enlargement of the liver and spleen. Most are stillborn, or die within a few days of birth. Carrying an Hb Bart fetus may be harmful to the mother. HbH disease involves moderate anemia, jaundice, and enlargement of the liver and spleen. Abnormal skeletal changes are sometimes seen. Symptoms may begin in either childhood or adulthood. Generally, those with HbH can live a near-normal lifespan, although some may need blood transfusions if anemia becomes severe. The inheritance of the faulty genes is complex, but involves a number of categories of both carriers and those with symptoms. The disease is relatively common, particularly in South-East Asia. Other regions badly affected include India, the Middle East, Africa, and Mediterranean countries. Worldwide, about 1 in 48 people are carriers for the condition.
Sources
NIH, Genetics Home Reference: HBA1 gene.
See http://ghr.nlm.nih.gov/gene/HBA1
NIH, Genetics Home Reference: HBA2 gene.
See http://ghr.nlm.nih.gov/gene/HBA2
NIH, Genetics Home Reference: Alpha-thalassemia.
See http://ghr.nlm.nih.gov/condition/alpha-thalassemia
Origa, R. et al. (2005), “Alpha-Thalassemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1435/
Recombine Website. Alpha-thalassemia.
See https://recombine.com/diseases/alphathalassemia

Question 9

Beta Thalassemia (HBB)

Accepted Answer

Beta Thalassemia is caused by mutations in the HBB gene, which encodes for the protein beta-globin, a subunit of hemoglobin. There are two forms of the disease, beta thalassemia major and beta thalassemia intermedia, the latter being less severe. With beta thalassemia major, symptoms develop before the age of two. Severe anemia is common, necessitating frequent blood transfusions. Other symptoms include jaundice, skeletal defects, and enlargement of the heart, liver, and spleen. Delayed adolescence may occur. Over time, excess iron from transfusions builds up in the body, and needs to be removed by chelation drugs. Premature death from cardiac mortality is common, but decreasing as treatments improve. Thalassemia intermedia is associated with mild anemia, some skeletal abnormalities, and in some cases growth inhibition. The worldwide incidence of beta-thalassemia is 1 in 100,000 new births. Regions with high levels of the disease include Mediterranean countries, the Middle-East, Central Asia, Africa, and the Far East. In the USA, those whose ancestors came from these regions have a higher risk of the disease than other ethnic groups. The mutated gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.
Sources
NIH, Genetics Home Reference: HBB gene.
See http://ghr.nlm.nih.gov/gene/HBB
NIH, Genetics Home Reference: Beta-thalassemia.
See http://ghr.nlm.nih.gov/condition/beta-thalassemia
Origa, R. (2000), “Beta-Thalassemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1426/
Recombine Website. Beta-thalassemia.
See https://recombine.com/diseases/betathalassemia

Question 10

Mucolipidosis IV (MCOLN1)

Accepted Answer

Mucolipidosis type IV is a disease caused by defects in the MCOLN1 gene, which encodes for the protein mucolipin 1. This protein is found in the membranes of lysosomes and endosomes, and is involved in the transport of various molecules. Mucolipin 1 is essential for the development and maintenance of the brain and retina. Infants with the disease typically develop poor motor skills, being slow to crawl, and rarely learning to walk or speak properly. Sufferers may have muscle weakness and difficulties swallowing. Visual impairment gradually advances, usually leading to complete blindness before the age of 10. Iron deficiency may occur as well. A small number of sufferers, about 5% of the total, develop a milder form of the disease, where they may be able to walk and talk. People with mucolipidosis type IV may live for many decades, although they tend to have a shortened lifespan. Overall, it’s estimated that about 1 in 625,000 people suffer from mucolipidosis type IV, although the figure rises to 1 in 37,000 among those of Ashkenazi Jewish descent, where about 1 in 100 may be carriers. The faulty gene is inherited in an autosomal recessive manner, which typically requires both parents to be asymptomatic carriers of the faulty gene copy.
Sources
NIH, Genetics Home Reference: MCOLN1 gene.
See http://ghr.nlm.nih.gov/gene/MCOLN1
NIH, Genetics Home Reference: Mucolipidosis Type IV.
See http://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv
Recombine Website: Mucolipidosis Type IV.
See https://recombine.com/diseases/mucolipidosis-type-iv
Schiffmann, R. et al. (2005), “Mucolipidosis IV,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1214/

Question 11

Familial Dysautonomia (IKBKAP)

Accepted Answer

Familial dysautonomia is caused by defects in the IKBKAP gene. This gene encodes for a protein called IKK complex-associated protein, which plays a role in protein transcription. Nerve cells are adversely affected when the protein fails to function. Children with the disease typically suffer from gastrointestinal problems (such as vomiting), feeding difficulties, somewhat stunted growth, muscle weakness, and a lack of sensitivity to pain or temperature. Sufferers are liable to suffer from lung infections far more than normal. Curvature of the spine and deterioration in vision often occur. Walking becomes increasingly difficult as adulthood is reached, and many patients reach the point where they are no longer able to walk unaided. Kidney damage is also common during adulthood. Early death is likely, often due to lung infections, although improvements to treatment mean that around half of all patients now survive to age 40. Familial Dysautonomia is normally found in those of Ashkenazi Jewish descent, where about 1 in 3,700 are affected; approximately 1 in 36 are carriers. The mutated gene is inherited in an autosomal recessive manner, which typically requires both parents to be asymptomatic carriers of the faulty gene copy. However, there have been cases of both male and female sufferers having children, although pregnancy is high risk for those with the condition. The offspring between affected patients and non-carriers will normally be asymptomatic carriers.
Sources
NIH, Genetics Home Reference: Familial Dysautonomia.
See http://ghr.nlm.nih.gov/condition/familial-dysautonomia
NIH, Genetics Home Reference: IKBKAP gene.
See http://ghr.nlm.nih.gov/gene/IKBKAP
Recombine Website: Familial Dysautonomia.
See https://recombine.com/diseases/familial-dysautonomia
Shohat, M. & Weisz Hubshman, M. (2003), “Familial Dysautonomia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1180/

Question 12

Glycogen Storage Disease II (GAA)

Accepted Answer

Glycogen storage disease II, also known as Pompe disease, is caused by mutations in the GAA gene. This gene encodes for the enzyme alpha-glucosidase, which breaks down glycogen into glucose. Without this enzyme, glycogen can build up to toxic levels, damaging muscles, including the heart muscles, as well as an inability to maintain normal fasting glucose levels. The classic form of the disease emerges in the first few months of life. Babies exhibit muscle weakness, breathing difficulties, heart problems, and fail to thrive. Mortality rates are high, few surviving the first year without treatment. A “non-classic” infantile form appears in the first year of life. Symptoms are similar, but the heart tends to be less severely affected. Even so, breathing difficulties mean that few survive for more than a few years without treatment. A late-onset form of the disease is also known, in which symptoms first appear during late childhood, adolescence, or adulthood. Here muscle weakness and respiratory problems arise, but usually the heart is unaffected. Most sufferers from this form die within 30 years of diagnosis without treatment. Enzyme replacement therapy, along with treatment for the various symptoms, can extend survival to some extent. The incidence of glycogen storage disease type II is around 1 in 40,000 in the USA, rising to 1 in 14,000 among African Americans. The carrier rate reaches about 1 in 60 in the latter population. The defective genes are inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers for the faulty gene.
Sources
Leslie, N. & Tinkle, B.T. (2007), “Glycogen Storage Disease Type II (Pompe Disease),” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1261/
NIH, Genetics Home Reference: GAA gene.
See http://ghr.nlm.nih.gov/gene/GAA
NIH, Genetics Home Reference: Pompe Disease.
See http://ghr.nlm.nih.gov/condition/pompe-disease
Recombine Website: Glycogen Storage Disease, Type 2.
See https://recombine.com/diseases/glycogen-storage-disease-type-ii

Question 13

Classical Galactosemia (GALT)

Accepted Answer

Classical galactosemia is caused by mutations in the GALT gene. This gene encodes for the enzyme galactose-1-phosphate uridyltransferase, which is one of the enzymes that break down galactose. If the enzyme fails to function, increasing amounts of galactose-1-phosphate build up in the body, causing damage to tissues. The symptoms usually appear in the first few days of life. Babies suffer from vomiting, diarrhea, liver damage, jaundice, and fail to thrive. They are more susceptible to infection from bacteria such as E. coli than normal. Untreated babies usually die, or have severe brain damage. Feeding babies from birth on lactose-free formula milk is necessary. As they get older, a special diet absent of galactose and lactose is necessary. Even so, treated children are still at risk of poor growth, eye and speech problems, and mild intellectual disability. Women tend to suffer from premature ovarian insufficiency, so may not be able to have children. A “clinical variant” galactosemia, with slightly milder symptoms and without the increased risk of bacterial infection, has been described. This is also caused by defects in the GALT gene. Other types of galactosemia are caused by defects in other genes. The incidence of classical galactosemia has been estimated as 1 in 10,000 to 1 in 48,000 in the general population. The disease is particularly common among Irish travelers and their descendants, where up to 1 in 14 may be carriers, compared to about 1 in 125 in the general population. The “clinical variant” form is mainly found in African Americans. The disease is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene. If a sufferer has children with a partner who is not a carrier for the disease, the children will be asymptomatic carriers.
Sources
Berry, G.T. (2000), “Classic Galactosemia and Clinical Variant Galactosemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1518/
NIH, Genetics Home Reference: Galactosemia.
See http://ghr.nlm.nih.gov/condition/galactosemia
NIH, Genetics Home Reference: GALT gene.
See http://ghr.nlm.nih.gov/gene/GALT
Recombine Website: Classical Galactosemia.
See https://recombine.com/diseases/classical-galactosemia

Question 14

Ornithine Transcarbamylase Deficiency (OTC)

Accepted Answer

Ornithine transcarbamylase deficiency is caused by mutations in the OTC gene. This gene encodes for the enzyme ornithine transcarbamylase, which carries out a key step in the urea cycle. The liver alters toxic ammonia and converts it to urea, a much safer is converted into urea, a much more neutral compound. If the enzyme is partially or wholly inactivated, damaging levels of ammonia will tend to build up in the body. The condition is much more common in males than females. Symptoms often occur within the first few days of life. They include poor feeding, muscle weakness, lethargy, seizures, and hyperventilation. Severe hypothermia and brain damage result if prompt treatment is not started. Dialysis and nitrogen scavenger compounds, such as sodium benzoate, can be used to remove ammonia from the body. Even when ammonia levels appear to be under control, a crisis can appear in which they become elevated again. Low protein diets are needed throughout life. Infants may even require a liver transplant. A late-onset form of the disease can commence later in life, sometimes triggered by injuries, operations, or starting a high protein diet. Typical symptoms include mental problems, headaches, and vomiting. The incidence of the disease is roughly 1 in 70,000 births, occurring in roughly 4,300 patients in the USA. There does not seem to be huge differences in its occurrence among different ethnic groups. The faulty gene resides on the X chromosome, also known as an X-linked disease. Unlike females, any male with the faulty gene will have the disease since males only have a single X chromosome. The severe version of the disease is very rare in females, since they would need two faulty genes, which is highly unlikely. Females with one faulty gene normally act as carriers with no symptoms, however 15% of them will show some symptoms during their lifetime. As the disease is linked to the X chromosome, affected fathers cannot pass it on to their sons. Their daughters of affected fathers will normally receive the faulty gene.. Mothers with the faulty gene, whether they are asymptomatic or not, have a 50% chance of passing it on to each child.
Sources
Lichter-Konecki, U. et al. (2013), “Ornithine Transcarbamylase Deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK154378/
NIH, Genetics Home Reference: Ornithine Transcarbamylase Deficiency.
See http://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency
NIH, Genetics Home Reference: OTC gene.
See http://ghr.nlm.nih.gov/gene/OTC
Recombine Website: Ornithine Transcarbamylase Deficiency.
See https://recombine.com/diseases/ornithine-transcarbamylase-deficiency

Recursos> Preguntas frecuentes

Frequently asked questions

Tay-Sachs (HEXA)

Canavan Disease (ASPA) ures in my FAQ?

Sickle Cell Disease (HBB)

Gaucher Disease (GBA)

Phenylketonuria (PAH)

Glycogen Storage Disease II (GAA)

Alpha Thalassemia (HBA1 / HBA2)

Beta Thalassemia (HBB)

Mucolipidosis IV (MCOLN1)

Familial Dysautonomia (IKBKAP)

Glycogen Storage Disease II (GAA)

Classical Galactosemia (GALT)

Ornithine Transcarbamylase Deficiency (OTC)