Genetic Disorders and Biochemical Pathology Indian Medical PG Practice Questions and MCQs
Practice Indian Medical PG questions for Genetic Disorders and Biochemical Pathology. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Genetic Disorders and Biochemical Pathology Indian Medical PG Question 1: An infant presented with vomiting, malnutrition, blue eyes, blonde hair & fair skin. On investigation, Guthrie test was positive. All are true regarding this disease EXCEPT:
- A. Phenyl acetate positive in urine
- B. Mental retardation is present
- C. Hypopigmentation due to tryptophan deficiency (Correct Answer)
- D. Due to PAH enzyme defect
Genetic Disorders and Biochemical Pathology Explanation: ***Hypopigmentation due to tryptophan deficiency***
- The characteristic **hypopigmentation** (fair skin, blonde hair, blue eyes) in **phenylketonuria (PKU)** is due to **tyrosine deficiency**, not tryptophan deficiency.
- **Phenylalanine hydroxylase (PAH)** deficiency leads to accumulation of phenylalanine, which cannot be converted to **tyrosine**.
- **Tyrosine** is the precursor for **melanin synthesis** via the enzyme **tyrosinase**, so tyrosine deficiency results in decreased melanin production and hypopigmentation.
*Phenyl acetate positive in urine*
- In **phenylketonuria (PKU)**, **phenylalanine** accumulates and is shunted to alternative metabolic pathways, leading to the production and excretion of **phenylacetate, phenylpyruvate, and phenyllactate** in the urine.
- The presence of these metabolites gives the urine a characteristic **mousey or musty odor**.
*Mental retardation is present*
- If **phenylketonuria (PKU)** is left untreated, the accumulation of **phenylalanine** is neurotoxic and leads to severe, **irreversible intellectual disability** and **developmental delay**.
- Early detection through newborn screening (the **Guthrie test** detects elevated blood phenylalanine) and dietary phenylalanine restriction are crucial to prevent this outcome.
*Due to PAH enzyme defect*
- **Phenylketonuria (PKU)** is primarily caused by a deficiency in the enzyme **phenylalanine hydroxylase (PAH)**, which is responsible for converting phenylalanine to tyrosine.
- This **autosomal recessive genetic disorder** leads to the accumulation of phenylalanine in the blood and tissues, causing the clinical manifestations.
Genetic Disorders and Biochemical Pathology Indian Medical PG Question 2: Which one of the following is an autosomal recessive disease?
- A. Retinitis pigmentosa
- B. Vitamin D resistant rickets
- C. Cystic fibrosis (Correct Answer)
- D. Neurofibromatosis
Genetic Disorders and Biochemical Pathology Explanation: ***Cystic fibrosis***
- **Cystic fibrosis** is caused by mutations in the **CFTR gene**, leading to defective chloride transport and thick, sticky mucus.
- It is inherited in an **autosomal recessive pattern**, meaning an individual must inherit two copies of the mutated gene (one from each parent) to develop the disease.
*Retinitis pigmentosa*
- **Retinitis pigmentosa** is a group of inherited eye disorders, and while some forms are X-linked or autosomal dominant, a significant portion are also inherited in an **autosomal recessive pattern**.
- However, it's not exclusively autosomal recessive, making cystic fibrosis a more definitive answer in this context.
*Vitamin D resistant rickets*
- **Vitamin D resistant rickets**, also known as **X-linked hypophosphatemic rickets**, is primarily inherited in an **X-linked dominant pattern**.
- It is characterized by impaired renal phosphate reabsorption and skeletal abnormalities despite normal vitamin D levels.
*Neurofibromatosis*
- **Neurofibromatosis type 1 (NF1)** and **Neurofibromatosis type 2 (NF2)** are both inherited in an **autosomal dominant pattern**.
- NF1 is characterized by **café-au-lait spots**, **neurofibromas**, and optical gliomas, while NF2 involves **bilateral vestibular schwannomas**.
Genetic Disorders and Biochemical Pathology Indian Medical PG Question 3: Which one of the following conditions can be screened during neonatal screening by biochemical tests?
- A. Congenital dislocation of hip
- B. Congenital rubella
- C. Chromosomal abnormalities
- D. Congenital hypothyroidism (Correct Answer)
Genetic Disorders and Biochemical Pathology Explanation: ***Congenital hypothyroidism***
- **Neonatal screening** for congenital hypothyroidism is a standard practice, using biochemical tests to measure **thyroid-stimulating hormone (TSH)** and **thyroxine (T4)** levels in dried blood spots.
- Early detection and treatment prevent severe **intellectual disability** and developmental delays caused by thyroid hormone deficiency.
*Congenital dislocation of hip*
- This condition is primarily screened through **physical examination** (e.g., Ortolani and Barlow maneuvers) and imaging (e.g., ultrasound), not biochemical tests.
- It involves a structural abnormality of the hip joint, not a metabolic or biochemical disorder.
*Congenital rubella*
- Diagnosis of congenital rubella involves detecting **rubella-specific IgM antibodies** or viral RNA, which are immunological/virological tests, not typical biochemical screening.
- This is an infectious disease, not an inborn error of metabolism screened biochemically.
*Chromosomal abnormalities*
- Conditions like Down syndrome (Trisomy 21) are detected through **karyotyping** or **genetic tests**, which examine the number and structure of chromosomes.
- While some biochemical markers are used in prenatal screening for chromosomal abnormalities (e.g., quad screen), direct neonatal screening for chromosomal abnormalities is not performed via general biochemical tests.
Genetic Disorders and Biochemical Pathology Indian Medical PG Question 4: Glutamine is increased in CSF, blood & urine WITHOUT elevated orotic acid in which defect:
- A. Arginase
- B. Argininosuccinate lyase deficiency
- C. CPS-I (Correct Answer)
- D. Arginosuccinate synthetase
- E. OTC
Genetic Disorders and Biochemical Pathology Explanation: ***CPS-I***
- A deficiency in **Carbamoyl Phosphate Synthetase I (CPS-I)** leads to a severe block in the **urea cycle**, resulting in profound hyperammonemia.
- The elevated ammonia is then shunted to produce more **glutamine** (via glutamine synthetase), which serves as a detoxification mechanism but also causes high levels of glutamine in CSF, blood, and urine.
*Arginase*
- **Arginase deficiency** primarily leads to elevated **arginine** levels and mild to moderate hyperammonemia, but not typically a dramatic increase in glutamine due to the block occurring later in the cycle.
- Clinical features include progressive spasticity, growth retardation, and intellectual disability.
*Argininosuccinate lyase deficiency*
- This deficiency causes accumulation of **argininosuccinate** in body fluids, which is a diagnostic marker, rather than primarily increased glutamine.
- It presents with severe hyperammonemia, neurological symptoms, and often hepatomegaly.
*Arginosuccinate synthetase*
- A deficiency in **argininosuccinate synthetase** (also known as citrullinemia type I) leads to a buildup of **citrulline** and severe hyperammonemia.
- While hyperammonemia can indirectly increase glutamine, the primary diagnostic marker is elevated citrulline, and the glutamine increase is not as pronounced or directly symptomatic as in CPS-I deficiency.
*OTC*
- **Ornithine Transcarbamylase (OTC) deficiency** is the most common urea cycle disorder and leads to severe hyperammonemia, accompanied by elevated **orotic acid** due to carbamoyl phosphate shunting to pyrimidine synthesis.
- While hyperammonemia drives glutamine synthesis, the presence of elevated orotic acid is a key differentiator from CPS-I deficiency, which does not have increased orotic acid.
Genetic Disorders and Biochemical Pathology Indian Medical PG Question 5: Phenylketonuria is due to deficiency of:
- A. Phenylalanine (amino acid)
- B. Tyrosine
- C. Phenylalanine hydroxylase (PAH) (Correct Answer)
- D. None of the options
Genetic Disorders and Biochemical Pathology Explanation: ***Phenylalanine hydroxylase (PAH)***
- **Phenylketonuria (PKU)** is an inherited metabolic disorder caused by a deficiency of the enzyme **phenylalanine hydroxylase (PAH)**.
- This enzyme is crucial for converting the amino acid **phenylalanine** into **tyrosine**, and its deficiency leads to an accumulation of phenylalanine in the body.
- PKU follows an **autosomal recessive** inheritance pattern.
*Phenylalanine (amino acid)*
- While **phenylalanine** accumulates to toxic levels in PKU, it is the substrate, not the deficient component.
- The disease stems from the body's inability to metabolize this amino acid due to the enzyme deficiency.
*Tyrosine*
- **Tyrosine** is the product of the reaction catalyzed by PAH, and its production is limited in PKU.
- However, the deficiency of tyrosine is a secondary effect, not the primary cause of PKU.
*None of the options*
- This option is incorrect because the deficiency of **phenylalanine hydroxylase (PAH)** is precisely the cause of Phenylketonuria.
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