Question

Using albinism and phenylketonuria as examples, explain what is meant by inborn errors of metabolism.

Short answer

Inborn errors of metabolism are rare genetic disorders caused by mutations in enzymes or transport proteins involved in metabolic pathways, leading to the accumulation of toxic substances or an inability to synthesize essential molecules. Albinism occurs due to mutations in genes responsible for melanin production and distribution, specifically involving the enzyme tyrosinase, which converts tyrosine into melanin. Phenylketonuria (PKU) results from a deficiency in the enzyme phenylalanine hydroxylase, which is responsible for converting phenylalanine into tyrosine, causing phenylalanine accumulation in the blood. Both albinism and PKU exemplify how genetic mutations can disrupt metabolic pathways, leading to various health issues.

Step-by-step solution

Define inborn errors of metabolism

Inborn errors of metabolism are a group of rare genetic disorders that occur when a person's body is unable to properly break down certain substances (usually amino acids, sugars, or lipids) due to mutations in specific enzymes or transport proteins involved in metabolic pathways. These mutations often lead to the accumulation of toxic substances in the body and/or an inability to synthesize essential molecules.

Explain albinism as an example of an inborn error of metabolism

Albinism is a genetic disorder caused by mutations in the genes responsible for the production and distribution of melanin, the pigment responsible for color in the skin, hair, and eyes. In albinism, the absence or reduction of melanin production leads to a lack of pigmentation, which can cause various health issues including photosensitivity, vision problems, and an increased risk of skin cancer. The metabolic pathway implicated in albinism involves the enzyme tyrosinase, which catalyzes the conversion of tyrosine (an amino acid) into melanin. Mutations in the tyrosinase gene or related genes can result in the improper function or production of this enzyme, leading to the characteristic lack of pigmentation in albinism.

Explain phenylketonuria (PKU) as another example of an inborn error of metabolism

Phenylketonuria (PKU) is another genetic disorder characterized by the accumulation of the amino acid phenylalanine in the body due to a deficiency of the enzyme phenylalanine hydroxylase. This enzyme is responsible for converting phenylalanine into another amino acid called tyrosine. When the enzyme is not functioning properly, phenylalanine accumulates in the blood and can lead to severe intellectual disability, seizures, and other developmental issues if not treated early. In PKU, the metabolic pathway affected involves the conversion of phenylalanine into tyrosine by phenylalanine hydroxylase. Mutations in the gene encoding for this enzyme result in reduced or absent activity, leading to the characteristic accumulation of phenylalanine in the blood and urine. In summary, inborn errors of metabolism such as albinism and phenylketonuria are caused by genetic mutations that affect specific enzymes or transport proteins involved in metabolic pathways. These mutations can lead to the accumulation of potentially toxic substances or an inability to synthesize essential molecules, resulting in various health issues.

Key concepts

Genetic Disorders

Genetic disorders are health conditions caused by alterations in an individual's DNA. These changes can be inherited from one or both parents or can occur spontaneously. Genetic disorders can affect numerous physiological functions and are often categorized based on the type of mutation or the metabolic pathway affected. Types of Genetic Disorders:

• Single-Gene Disorders: Caused by a mutation in a single gene, such as cystic fibrosis and sickle cell disease.
• Chromosomal Disorders: Involves missing or extra copies or structural changes in chromosomes, like Down syndrome.
• Multifactorial Disorders: Results from mutations in multiple genes often coupled with environmental influences, like heart disease.

Inborn errors of metabolism represent a subset of genetic disorders. They occur due to gene mutations leading to enzyme deficiencies, disrupting normal metabolic processes. As a result, substances required for normal body function accumulate or are inadequately synthesized, causing various health complications.

Albinism

Albinism is a genetic disorder that results in a noticeable lack of pigmentation in the skin, hair, and eyes. This occurs due to mutations affecting melanin production. Understanding Albinism Mechanism:

• Melanin is the pigment responsible for color in the skin, hair, and eyes.
• In albinism, the enzyme tyrosinase, which converts the amino acid tyrosine into melanin, is affected.
• Mutations in the tyrosinase gene (or related genes) lead to reduced or absent enzyme activity.

This results in visible symptoms of albinism, such as light-colored skin and hair. Some individuals also face health issues like:

• Vision Problems: Due to abnormal development of the retina and optic nerve pathways.
• Photosensitivity: Increased sensitivity to sunlight, leading to discomfort and a higher risk of skin damage.
• Skin Cancer Risk: Reduced melanin increases susceptibility to UV radiation and, consequently, skin cancer.

Albinism serves as an example of how genetic mutations can impact biochemical pathways, leading to varied physiological effects.

Phenylketonuria

Phenylketonuria (PKU) is a metabolic genetic disorder, most well-known for the accumulation of phenylalanine, an amino acid, due to an enzyme deficiency. Mechanism of PKU:

• The enzyme phenylalanine hydroxylase is crucial for converting phenylalanine into tyrosine.
• Mutations in the gene for this enzyme reduce its activity, leading to an overabundance of phenylalanine in the blood.
• Excess phenylalanine is harmful, particularly affecting the brain and nervous system development.

Untreated PKU can result in severe consequences such as:

• Intellectual Disabilities: High levels of phenylalanine can lead to brain damage and cognitive impairments.
• Developmental Delays: Individuals may experience delayed milestones in development.
• Behavioral Problems: Including hyperactivity and social challenges.

Newborn screening allows for early detection, enabling interventions such as low-phenylalanine diets to prevent complications. PKU demonstrates how crucial metabolic enzymes are in regulating amino acid levels and maintaining neurological health.