1) Aspartylglycosaminuria
a) What is the inheritance pattern of this disease;
Aspartylglucosaminuria is a genetic condition that is inherited from both parents. The AGU
patient is born with two copies of the mutated AGA gene. One copy comes from the mother’s
egg and the other copy comes from the father’s sperm In order to develop
aspartylglucosaminuria, the individual must inherit changes in both of his AGU genes
(autonomic recessive inheritance). When a person receives one changed form of the gene AGU
from one of the parents, the individual is then classified as a carrier.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Aspartylglucosaminuria is estimated to affect 1 in 18,500 people in Finland. This condition is
less common in other countries, but the incidence is unknown.Even though this disease can occur
in various races and ethnicities, another study backed this finding up by stating that 1 in 26,000
people in Finland had the disease and that 1 in 18,000 were carriers.
After trisomy 21 and fragile X syndrome, this is the most frequent multiple congenital
anomaly/mental retardation syndrome in Finland
c) What is the biochemical defect that causes this disease? (15 points)
The disease is caused by a defect in an enzyme known as aspartylglucosaminidase. This enzyme
plays a significant role in our bodies because it aids in breaking down certain sugars (for
example,oligosaccharides) that are attached to specific proteins (for example, glycoproteins).
Aspartylglucosaminuria itself is characterized as a lysosomal disease because it does deal with
inadequate activity in an enzyme\'s function. Aspartylglucosaminidase functions to break down
glycoproteins. These proteins are most abundant in the tissues of the body and in the surfaces of
major organs, such as theliver, spleen, thyroid and nerves. When glycoproteins are not broken
down, aspartylglucosaminidase backs up in the lysosomes along with other substances. This
backup causes progressive damage to the tissues and organs
2) Alpha-mannosidosis
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
The worldwide incidence of alpha-mannosidosis is in the range of 1 per 500,000 to 1 per
1,000,000. Mannosidosis is found in all ethnic groups in Europe, America, Africa, and Asia.
c) What is the biochemical defect that causes this disease? (15 points)
Alpha-mannosidosis is a lysosomal storage disorder caused by deficient activity of the enzyme
alpha-D-mannosidase. In humans it is known to be caused by an autosomal recessive genetic
mutation. In lives.
1) Aspartylglycosaminuriaa) What is the inheritance pattern of thi.pdf
1. 1) Aspartylglycosaminuria
a) What is the inheritance pattern of this disease;
Aspartylglucosaminuria is a genetic condition that is inherited from both parents. The AGU
patient is born with two copies of the mutated AGA gene. One copy comes from the mother’s
egg and the other copy comes from the father’s sperm In order to develop
aspartylglucosaminuria, the individual must inherit changes in both of his AGU genes
(autonomic recessive inheritance). When a person receives one changed form of the gene AGU
from one of the parents, the individual is then classified as a carrier.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Aspartylglucosaminuria is estimated to affect 1 in 18,500 people in Finland. This condition is
less common in other countries, but the incidence is unknown.Even though this disease can occur
in various races and ethnicities, another study backed this finding up by stating that 1 in 26,000
people in Finland had the disease and that 1 in 18,000 were carriers.
After trisomy 21 and fragile X syndrome, this is the most frequent multiple congenital
anomaly/mental retardation syndrome in Finland
c) What is the biochemical defect that causes this disease? (15 points)
The disease is caused by a defect in an enzyme known as aspartylglucosaminidase. This enzyme
plays a significant role in our bodies because it aids in breaking down certain sugars (for
example,oligosaccharides) that are attached to specific proteins (for example, glycoproteins).
Aspartylglucosaminuria itself is characterized as a lysosomal disease because it does deal with
inadequate activity in an enzyme's function. Aspartylglucosaminidase functions to break down
glycoproteins. These proteins are most abundant in the tissues of the body and in the surfaces of
major organs, such as theliver, spleen, thyroid and nerves. When glycoproteins are not broken
down, aspartylglucosaminidase backs up in the lysosomes along with other substances. This
backup causes progressive damage to the tissues and organs
2) Alpha-mannosidosis
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
The worldwide incidence of alpha-mannosidosis is in the range of 1 per 500,000 to 1 per
2. 1,000,000. Mannosidosis is found in all ethnic groups in Europe, America, Africa, and Asia.
c) What is the biochemical defect that causes this disease? (15 points)
Alpha-mannosidosis is a lysosomal storage disorder caused by deficient activity of the enzyme
alpha-D-mannosidase. In humans it is known to be caused by an autosomal recessive genetic
mutation. In livestock it is caused by chronic poisoning with swainsonine from locoweed.
A defective alpha-mannosidase enzyme, which normally helps to break down complex sugars
derived from glycoproteins in the lysosome, causes sugar build up and impairs cell function.
Complete absence of functionality in this enzyme leads to death during early childhood due to
deterioration of the central nervous system. Enzymes with low residual activity lead to a milder
type of the disease, with symptoms like reduced hearing, mental disabilities, susceptibility to
bacterial infections, and skeletal deformities. The course of the disease is progressive.
Alpha-mannosidosis is classified into types I through III based on severity and age of onset. In
contrast to the usual classifications scheme of these disorders, type III is the most severe.
3) Beta-mannosidosis
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition. 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,
however because it is so rare, the fullphenotype associated with the disease is not fully
understood.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Beta-mannosidosis is believed to be a very rare disorder. Approximately 20 affected individuals
have been reported worldwide. It is difficult to determine the specific incidence of beta-
mannosidosis, because people with mild or non-specific symptoms may never be diagnosed.
c) What is the biochemical defect that causes this disease? (15 points)
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.
4) Sandhoff-Jatzkewitz disease
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
gene in each cell have mutations. The parents of an individual with an autosomal recessive
3. condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Sandhoff disease is a rare disorder; its frequency varies among populations. This condition
appears to be more common in the Creole population of northern Argentina; the Metis Indians in
Saskatchewan, Canada; and people from Lebanon.
c) What is the biochemical defect that causes this disease? (15 points)
Sandhoff disease, also known as Sandhoff-Jatzkewitz disease, variant 0 of GM2-Gangliosidosis
or Hexosaminidase A and B deficiency, 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
5) Sialidosis
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Sialidosis affects males and females in equal numbers. The exact incidence of sialidosis in the
general population is unknown. One estimate places the incidence at 1 in 4.2 million individuals
in the Australian population. Another estimate placed the incidence at 1-4 individuals per
200,000 of the general population. Because rare disorders like sialidosis often go unrecognized
or misdiagnosed, determining the true frequency of sialidosis in the general population is
difficult.
c) What is the biochemical defect that causes this disease? (15 points)
Mucolipidosis type I (ML I) or sialidosis is an inherited lysosomal storage disease that results
from a deficiency of the enzyme alpha-N -acetylneuraminidase (sialidase).The lack of this
enzyme results in an abnormal accumulation of complex carbohydrates known as
mucopolysaccharides, and of fatty substances known as mucolipids. Both of these substances
accumulate in bodily tissues.
4. Solution
1) Aspartylglycosaminuria
a) What is the inheritance pattern of this disease;
Aspartylglucosaminuria is a genetic condition that is inherited from both parents. The AGU
patient is born with two copies of the mutated AGA gene. One copy comes from the mother’s
egg and the other copy comes from the father’s sperm In order to develop
aspartylglucosaminuria, the individual must inherit changes in both of his AGU genes
(autonomic recessive inheritance). When a person receives one changed form of the gene AGU
from one of the parents, the individual is then classified as a carrier.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Aspartylglucosaminuria is estimated to affect 1 in 18,500 people in Finland. This condition is
less common in other countries, but the incidence is unknown.Even though this disease can occur
in various races and ethnicities, another study backed this finding up by stating that 1 in 26,000
people in Finland had the disease and that 1 in 18,000 were carriers.
After trisomy 21 and fragile X syndrome, this is the most frequent multiple congenital
anomaly/mental retardation syndrome in Finland
c) What is the biochemical defect that causes this disease? (15 points)
The disease is caused by a defect in an enzyme known as aspartylglucosaminidase. This enzyme
plays a significant role in our bodies because it aids in breaking down certain sugars (for
example,oligosaccharides) that are attached to specific proteins (for example, glycoproteins).
Aspartylglucosaminuria itself is characterized as a lysosomal disease because it does deal with
inadequate activity in an enzyme's function. Aspartylglucosaminidase functions to break down
glycoproteins. These proteins are most abundant in the tissues of the body and in the surfaces of
major organs, such as theliver, spleen, thyroid and nerves. When glycoproteins are not broken
down, aspartylglucosaminidase backs up in the lysosomes along with other substances. This
backup causes progressive damage to the tissues and organs
2) Alpha-mannosidosis
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
5. The worldwide incidence of alpha-mannosidosis is in the range of 1 per 500,000 to 1 per
1,000,000. Mannosidosis is found in all ethnic groups in Europe, America, Africa, and Asia.
c) What is the biochemical defect that causes this disease? (15 points)
Alpha-mannosidosis is a lysosomal storage disorder caused by deficient activity of the enzyme
alpha-D-mannosidase. In humans it is known to be caused by an autosomal recessive genetic
mutation. In livestock it is caused by chronic poisoning with swainsonine from locoweed.
A defective alpha-mannosidase enzyme, which normally helps to break down complex sugars
derived from glycoproteins in the lysosome, causes sugar build up and impairs cell function.
Complete absence of functionality in this enzyme leads to death during early childhood due to
deterioration of the central nervous system. Enzymes with low residual activity lead to a milder
type of the disease, with symptoms like reduced hearing, mental disabilities, susceptibility to
bacterial infections, and skeletal deformities. The course of the disease is progressive.
Alpha-mannosidosis is classified into types I through III based on severity and age of onset. In
contrast to the usual classifications scheme of these disorders, type III is the most severe.
3) Beta-mannosidosis
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition. 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,
however because it is so rare, the fullphenotype associated with the disease is not fully
understood.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Beta-mannosidosis is believed to be a very rare disorder. Approximately 20 affected individuals
have been reported worldwide. It is difficult to determine the specific incidence of beta-
mannosidosis, because people with mild or non-specific symptoms may never be diagnosed.
c) What is the biochemical defect that causes this disease? (15 points)
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.
4) Sandhoff-Jatzkewitz disease
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
6. gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Sandhoff disease is a rare disorder; its frequency varies among populations. This condition
appears to be more common in the Creole population of northern Argentina; the Metis Indians in
Saskatchewan, Canada; and people from Lebanon.
c) What is the biochemical defect that causes this disease? (15 points)
Sandhoff disease, also known as Sandhoff-Jatzkewitz disease, variant 0 of GM2-Gangliosidosis
or Hexosaminidase A and B deficiency, 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
5) Sialidosis
a) What is the inheritance pattern of this disease;
This condition is inherited in an autosomal recessive pattern, which means both copies of the
gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition.
b) What is the incidence of this disease in the USA, i.e. what fraction of the population is
affected;
Sialidosis affects males and females in equal numbers. The exact incidence of sialidosis in the
general population is unknown. One estimate places the incidence at 1 in 4.2 million individuals
in the Australian population. Another estimate placed the incidence at 1-4 individuals per
200,000 of the general population. Because rare disorders like sialidosis often go unrecognized
or misdiagnosed, determining the true frequency of sialidosis in the general population is
difficult.
c) What is the biochemical defect that causes this disease? (15 points)
Mucolipidosis type I (ML I) or sialidosis is an inherited lysosomal storage disease that results
from a deficiency of the enzyme alpha-N -acetylneuraminidase (sialidase).The lack of this
enzyme results in an abnormal accumulation of complex carbohydrates known as
mucopolysaccharides, and of fatty substances known as mucolipids. Both of these substances
accumulate in bodily tissues.