The Biochemical Basis of Genetic Disorders: Understanding Phenylketonuria, Albinism and Sickle Cell Anemia
Introduction
Genetic disorders arise due to mutations in specific genes, affecting the biochemical pathways within the human body. Some of these conditions result from enzyme deficiencies, structural protein abnormalities, or metabolic dysfunctions. Among the many inherited disorders, Phenylketonuria (PKU), Albinism, and Sickle Cell Anemia are three well-known conditions with profound biochemical and physiological consequences. This study module explores the molecular basis of these disorders, their biochemical implications, and their effects on human health.
Causes of Phenylketonuria disease,
Albinism symptoms and diagnosis,
Sickle cell anemia complications,
Biochemical basis of PKU,
Genetic mutations in albinism.
1. Phenylketonuria (PKU)
Overview
Phenylketonuria (PKU) is an inherited metabolic disorder caused by a mutation in the PAH (phenylalanine hydroxylase) gene, leading to an inability to metabolize phenylalanine, an essential amino acid. If untreated, it results in severe neurological impairment.
Biochemical Basis of PKU
- The PAH gene encodes the enzyme phenylalanine hydroxylase, which converts phenylalanine into tyrosine.
- Mutations in PAH lead to enzyme deficiency, causing an accumulation of phenylalanine in the blood.
- Excess phenylalanine disrupts normal brain function, leading to intellectual disability, seizures, and behavioral problems.
Symptoms
- Intellectual disability (if untreated)
- Musty odor due to phenylketones in urine
- Developmental delays
- Skin disorders like eczema
Diagnosis & Treatment
- Newborn screening detects PKU early.
- Dietary restrictions: Avoid high-protein foods like meat, dairy, and nuts.
- Phenylalanine-free medical formulas supplement essential nutrients.
- Recent gene therapy and enzyme replacement therapy advancements offer potential treatments.
Relevant URL Links for More Information
2. Albinism
Overview
Albinism is a group of inherited disorders characterized by a lack of melanin production, resulting in pale skin, hair, and vision defects. It is primarily caused by mutations in the TYR gene, which encodes the enzyme tyrosinase, crucial for melanin synthesis.
Biochemical Basis of Albinism
- The TYR gene produces tyrosinase, an enzyme responsible for converting tyrosine into melanin.
- Mutations lead to a deficiency or complete absence of tyrosinase, halting melanin production.
- Reduced melanin affects skin pigmentation, hair color, and vision.
Symptoms
- Light-colored skin, hair, and eyes
- Poor vision and photophobia
- Increased risk of skin cancers
- Nystagmus (involuntary eye movements)
Diagnosis & Treatment
- Genetic testing confirms the disorder.
- Vision therapy and sun protection are essential for management.
- No definitive cure, but research on melanin-boosting therapies is ongoing.
Relevant URL Links for More Information
3. Sickle Cell Anemia
Overview
Sickle Cell Anemia is a genetic blood disorder caused by a mutation in the HBB gene, which encodes the beta-globin chain of hemoglobin. This leads to abnormal hemoglobin structure, causing red blood cells to assume a rigid, sickle shape, resulting in blockages in blood vessels and reduced oxygen transport.
Biochemical Basis of Sickle Cell Anemia
- The HBB gene mutation substitutes valine for glutamic acid in the hemoglobin protein.
- This altered hemoglobin (HbS) polymerizes under low oxygen conditions, causing red blood cells to become sickle-shaped.
- These cells have shorter lifespans and block capillaries, leading to pain, anemia, and organ damage.
Symptoms
- Severe pain episodes (sickle cell crisis)
- Chronic anemia and fatigue
- Increased risk of infections
- Stroke and organ damage
Diagnosis & Treatment
- Hemoglobin electrophoresis identifies abnormal hemoglobin.
- Hydroxyurea is used to increase fetal hemoglobin (HbF) production.
- Bone marrow transplantation is a potential cure.
- Blood transfusions and pain management help control symptoms.
Relevant URL Links for More Information
Conclusion
Genetic disorders like Phenylketonuria, Albinism, and Sickle Cell Anemia highlight the intricate relationship between biochemistry and genetics. Understanding the molecular basis of these conditions allows for better diagnosis, management, and potential therapeutic developments. Continued advancements in genetic research and biotechnology offer hope for more effective treatments and even cures for these hereditary diseases.
Further Reading
- Genetics Home Reference – NIH
- Mayo Clinic – Genetic Disorders
- National Human Genome Research Institute
- MedlinePlus – Genetic Conditions
MCQs on “Biochemical Basis of Genetic Disorders: Phenylketonuria, Albinism and Sickle Cell Anemia”
1. Phenylketonuria (PKU) is caused by a deficiency of which enzyme?
A) Tyrosinase
B) Phenylalanine hydroxylase ✅
C) Glucose-6-phosphate dehydrogenase
D) Homogentisate oxidase
Explanation: PKU is an autosomal recessive disorder caused by a mutation in the gene coding for phenylalanine hydroxylase (PAH), leading to an accumulation of phenylalanine and its toxic derivatives.
2. The primary treatment for Phenylketonuria is:
A) Insulin therapy
B) A low-phenylalanine diet ✅
C) Blood transfusion
D) Enzyme replacement therapy
Explanation: Since PKU patients cannot metabolize phenylalanine properly, they must follow a strict low-phenylalanine diet to prevent brain damage and intellectual disability.
3. Albinism is characterized by a deficiency in which pigment?
A) Hemoglobin
B) Carotene
C) Melanin ✅
D) Bilirubin
Explanation: Albinism occurs due to a lack of melanin, the pigment responsible for skin, hair, and eye color, due to defective tyrosinase enzyme activity.
4. The inheritance pattern of PKU is:
A) Autosomal dominant
B) Autosomal recessive ✅
C) X-linked dominant
D) X-linked recessive
Explanation: PKU is inherited in an autosomal recessive pattern, meaning a child must inherit two defective copies of the PAH gene (one from each parent) to develop the disorder.
5. Which of the following is the biochemical basis of Sickle Cell Anemia?
A) Deficiency of iron
B) Mutation in the β-globin gene ✅
C) Lack of folic acid
D) Deficiency of vitamin B12
Explanation: Sickle cell anemia is caused by a mutation in the β-globin gene (HBB) that leads to abnormal hemoglobin S (HbS), which distorts red blood cells into a sickle shape.
6. Which amino acid is substituted in Sickle Cell Anemia?
A) Valine is replaced by glutamic acid
B) Glutamic acid is replaced by valine ✅
C) Tyrosine is replaced by tryptophan
D) Glycine is replaced by alanine
Explanation: In Sickle Cell Anemia, a point mutation changes glutamic acid to valine at position 6 of the β-globin chain, causing hemoglobin molecules to polymerize and distort red blood cells.
7. The defective enzyme in Albinism is:
A) Phenylalanine hydroxylase
B) Tyrosinase ✅
C) Catalase
D) Peroxidase
Explanation: Albinism is caused by mutations in the tyrosinase gene (TYR), leading to the failure of melanin synthesis from tyrosine.
8. Phenylalanine accumulates in PKU due to its failure to convert into:
A) Tyrosine ✅
B) Dopamine
C) Melanin
D) Tryptophan
Explanation: In PKU, the absence of phenylalanine hydroxylase (PAH) prevents the conversion of phenylalanine to tyrosine, leading to toxic accumulation.
9. What type of mutation causes Sickle Cell Anemia?
A) Nonsense mutation
B) Frameshift mutation
C) Missense mutation ✅
D) Silent mutation
Explanation: Sickle Cell Anemia is caused by a missense mutation where glutamic acid (GAG) is replaced by valine (GTG) in the β-globin gene (HBB).
10. What is the major consequence of Sickle Cell Anemia?
A) Increased oxygen-carrying capacity
B) Formation of misshapen RBCs ✅
C) Uncontrolled bleeding
D) Increased clotting time
Explanation: The mutated hemoglobin (HbS) causes red blood cells to become rigid and sickle-shaped, leading to blockages in blood vessels and reduced oxygen transport.
11. Which chromosome carries the gene responsible for Phenylketonuria?
A) Chromosome 6
B) Chromosome 12 ✅
C) Chromosome 11
D) Chromosome 9
Explanation: The PAH gene responsible for PKU is located on chromosome 12 (12q23.2).
12. The inheritance pattern of Sickle Cell Anemia is:
A) Autosomal recessive ✅
B) Autosomal dominant
C) X-linked dominant
D) X-linked recessive
Explanation: Sickle Cell Anemia follows an autosomal recessive inheritance, meaning two copies of the mutant allele are required for disease manifestation.
13. Which population is most affected by Sickle Cell Anemia?
A) European
B) Asian
C) African ✅
D) Australian
Explanation: Sickle Cell Anemia is most common in African and Mediterranean populations, where it provides partial resistance to malaria.
14. Albinism is often associated with which vision problems?
A) Myopia
B) Astigmatism
C) Nystagmus and photophobia ✅
D) Hyperopia
Explanation: People with albinism often have nystagmus (involuntary eye movement) and photophobia (sensitivity to light) due to abnormal retinal development.
15. Which of the following is the best diagnostic test for Sickle Cell Anemia?
A) Hemoglobin electrophoresis ✅
B) Liver function test
C) Urine test
D) X-ray
Explanation: Hemoglobin electrophoresis identifies the abnormal hemoglobin (HbS) and distinguishes Sickle Cell Anemia from normal and carrier states.
16. Phenylketonuria (PKU) is diagnosed using which neonatal screening test?
A) Karyotyping
B) Guthrie test ✅
C) Western blot
D) ELISA
Explanation: The Guthrie test is a bacterial inhibition assay used for newborn screening of PKU by detecting elevated levels of phenylalanine in the blood.
17. What is the main symptom of untreated Phenylketonuria in infants?
A) Jaundice
B) Mental retardation ✅
C) Muscle weakness
D) Bone deformities
Explanation: If untreated, PKU leads to severe intellectual disability due to toxic buildup of phenylalanine in the brain.
18. Albinism primarily affects which organs the most?
A) Liver and kidneys
B) Skin and eyes ✅
C) Lungs and heart
D) Pancreas and spleen
Explanation: Albinism reduces melanin production, leading to light skin, white or pale hair, and vision problems due to underdeveloped retinal pigmentation.
19. Which vitamin is synthesized from tyrosine?
A) Vitamin A
B) Vitamin C
C) Vitamin D
D) Vitamin E ✅
Explanation: Tyrosine serves as a precursor for melanin, dopamine, and certain hormones but is not directly involved in vitamin D synthesis.
20. In Sickle Cell Anemia, which gas is less efficiently transported by red blood cells?
A) Oxygen ✅
B) Carbon dioxide
C) Nitrogen
D) Hydrogen
Explanation: The sickled shape of RBCs reduces their ability to carry oxygen, leading to tissue hypoxia and severe pain crises.
21. Why does Sickle Cell Anemia provide resistance against malaria?
A) The sickled cells destroy Plasmodium parasites ✅
B) It enhances immunity
C) It prevents mosquito bites
D) It strengthens blood vessels
Explanation: The abnormal HbS hemoglobin disrupts the life cycle of the malaria parasite (Plasmodium falciparum), reducing the severity of infection in heterozygous carriers.
22. Which medication is used to manage Sickle Cell Anemia by increasing fetal hemoglobin (HbF) production?
A) Aspirin
B) Hydroxyurea ✅
C) Insulin
D) Prednisone
Explanation: Hydroxyurea increases HbF (fetal hemoglobin) production, which helps prevent RBC sickling and reduces complications.
23. Phenylketonuria (PKU) is treated with supplementation of:
A) Tyrosine ✅
B) Leucine
C) Methionine
D) Lysine
Explanation: Since phenylalanine cannot be converted to tyrosine in PKU patients, they need tyrosine supplementation to compensate.
24. Which enzyme is blocked in Phenylketonuria (PKU)?
A) Phenylalanine hydroxylase ✅
B) Tyrosinase
C) Hexokinase
D) Lactase
Explanation: PKU results from a mutation in the PAH gene, leading to a deficiency of phenylalanine hydroxylase, which is necessary for converting phenylalanine to tyrosine.
25. Albinism is diagnosed through which method?
A) Genetic testing ✅
B) MRI scan
C) Blood sugar test
D) ECG
Explanation: Genetic testing can confirm albinism by identifying mutations in the TYR, OCA2, or other melanin-related genes.
26. Which gene is responsible for Sickle Cell Anemia?
A) HBB ✅
B) CFTR
C) PAH
D) G6PD
Explanation: The HBB gene mutation (β-globin gene) leads to abnormal hemoglobin S (HbS), causing Sickle Cell Anemia.
27. What is a major risk associated with untreated PKU?
A) Brain damage ✅
B) Liver failure
C) Muscle atrophy
D) Bone loss
Explanation: Phenylalanine accumulation in PKU causes severe brain damage and intellectual disability if untreated.
28. Which pigment is completely absent in Albinism?
A) Hemoglobin
B) Carotene
C) Melanin ✅
D) Myoglobin
Explanation: Albinism is characterized by a lack of melanin, the pigment responsible for skin, hair, and eye color.
29. PKU patients should avoid consuming:
A) High-protein foods ✅
B) Fruits
C) Vegetables
D) Fiber-rich foods
Explanation: High-protein foods like meat, eggs, and dairy contain phenylalanine, which PKU patients cannot metabolize properly.
30. What is the best way to prevent Sickle Cell Anemia in a population?
A) Genetic counseling ✅
B) Blood transfusion
C) Iron supplements
D) Vaccination
Explanation: Genetic counseling helps parents understand carrier status and risks, allowing them to make informed reproductive choices to prevent Sickle Cell Anemia.
