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Introduction
Inherited metabolic diseases (IMDs) are the large class of genetic disorders caused
by disruption of normal metabolic processes or by genetic mutations. Genes that
code the protein may be enzymes of metabolic processes affected by mutation and
results in loss of ability to provide normal products. IMDs do not include diseases
which are affected by modifications in structural proteins, membrane proteins, signal transduction between cells, transcription factors, and by hormone synthesis.
These consequences are also known as inborn errors of metabolism in which
enzymes are unable to perform normal body function. Many babies affected by
IMDs seem to be normal at birth but they show neurological signs and symptoms in
childhood. This disease causes mental retardation that leads to the death of newborns [1]. There are different types of pathomechanisms which are affected by partial or complete loss of enzymatic activity that leads to various metabolic disorders.
These include:
• Metabolites and toxic substances are accumulated
• Non-metabolized substrate is accumulated
• Deficiency of biochemical product
• Overproduction of biochemical product
• Insufficient production of ATP
There are many therapies that are used for the treatment of inherited metabolic
diseases. The well-known techniques used for the treatment of IMDs are recombinant enzyme replacement (ERT) therapy and hematopoietic stem cell transplantation (HSCT). These techniques are used to replace the defected genes to perform
normal metabolic process. However, limitations are applied to these therapies.
Moreover, the ERT is unable to cross blood–brain barrier and proved to be ineffective against neurological disorders [2]. So, other techniques like chaperone technology, gene therapy, and administration of ERT in spinal canal via injections in order
to make it more useful are under investigation [3].
Inheritance and Nosology of Inborn Metabolic Diseases
In 1902, Archibald Garrod was an English physician first discussed the inborn errors
of metabolism (IEMs) [4]. Most of the IEMs are autosomal recessive having two
defective genes in order to develop symptoms for the trait or disorder. More than six
hundred or seven hundreds of IEMs have been discovered since then [5]. In case of
autosomal dominant disease, there is only one defected gene present to develop a
disease [6].
Nosology refers to the classification of disorders [7]. There are hundreds of
inherited metabolic disorders caused by different genetic defects [8]. The largest
classes of inherited metabolic diseases are given in Table 4.1.
M. Shahid et al.
Introduction
Inherited metabolic diseases (IMDs) are the large class of genetic disorders caused
by disruption of normal metabolic processes or by genetic mutations. Genes that
code the protein may be enzymes of metabolic processes affected by mutation and
results in loss of ability to provide normal products. IMDs do not include diseases
which are affected by modifications in structural proteins, membrane proteins, signal transduction between cells, transcription factors, and by hormone synthesis.
These consequences are also known as inborn errors of metabolism in which
enzymes are unable to perform normal body function. Many babies affected by
IMDs seem to be normal at birth but they show neurological signs and symptoms in
childhood. This disease causes mental retardation that leads to the death of newborns [1]. There are different types of pathomechanisms which are affected by partial or complete loss of enzymatic activity that leads to various metabolic disorders.
These include:
• Metabolites and toxic substances are accumulated
• Non-metabolized substrate is accumulated
• Deficiency of biochemical product
• Overproduction of biochemical product
• Insufficient production of ATP
There are many therapies that are used for the treatment of inherited metabolic
diseases. The well-known techniques used for the treatment of IMDs are recombinant enzyme replacement (ERT) therapy and hematopoietic stem cell transplantation (HSCT). These techniques are used to replace the defected genes to perform
normal metabolic process. However, limitations are applied to these therapies.
Moreover, the ERT is unable to cross blood–brain barrier and proved to be ineffective against neurological disorders [2]. So, other techniques like chaperone technology, gene therapy, and administration of ERT in spinal canal via injections in order
to make it more useful are under investigation [3].
Inheritance and Nosology of Inborn Metabolic Diseases
In 1902, Archibald Garrod was an English physician first discussed the inborn errors
of metabolism (IEMs) [4]. Most of the IEMs are autosomal recessive having two
defective genes in order to develop symptoms for the trait or disorder. More than six
hundred or seven hundreds of IEMs have been discovered since then [5]. In case of
autosomal dominant disease, there is only one defected gene present to develop a
disease [6].
Nosology refers to the classification of disorders [7]. There are hundreds of
inherited metabolic disorders caused by different genetic defects [8]. The largest
classes of inherited metabolic diseases are given in Table 4.1.
M. Shahid et al.