Biochemical Diagnosis of Genetic Disorders — MCQs
The following cost-effective investigations are routinely recommended in the screening of antenatal mothers, EXCEPT:
Which is the best marker for NTD?
Which diagnostic tool is preferred for metabolic disease screening in children?
Which of the following statements about chorionic villus sampling is false?
A newborn presents with metabolic acidosis, high ammonia, and orotic acid in urine. Which enzyme deficiency is most likely?
A 5 year old child was brought to the physician with a history of black urine. There is no history of fever or any other complaints. There is no growth retardation and all the developmental milestones are normal. The child is suspected to have an enzyme defect for metabolism of an aromatic amino acid. What is the enzyme deficient
Which of the following techniques is used for the detection of variations in DNA sequence and gene expression?
What is the name of the treatment for type I tyrosinemia?
Increasing severity of intellectual disability of male members over generations is a result of ?
Which of the following is a sex-linked disorder?
Biochemical Diagnosis of Genetic Disorders Indian Medical PG Practice Questions and MCQs
Question 1: The following cost-effective investigations are routinely recommended in the screening of antenatal mothers, EXCEPT:
- A. Blood sugar levels for GDM
- B. VDRL for syphilis
- C. Urine analysis for bacteriuria
- D. Echocardiography for cardiac disease (Correct Answer)
Explanation: ***Echocardiography for cardiac disease*** - **Echocardiography** is not a *routinely recommended* screening investigation for all antenatal mothers due to its cost and the relatively low prevalence of significant congenital heart disease requiring universal screening. - It is typically performed only if there are **specific risk factors** or suspicious findings suggesting cardiac pathology. *Blood sugar levels for GDM* - Screening for **gestational diabetes mellitus (GDM)** with blood sugar levels (e.g., glucose challenge test) is routinely recommended due to the potential maternal and fetal complications if untreated. - GDM is a common condition that can be effectively managed with early diagnosis, making screening a **cost-effective** preventive measure. *VDRL for syphilis* - Screening for **syphilis** using tests like VDRL (Venereal Disease Research Laboratory) is a standard and *routinely recommended* antenatal investigation. - Early detection and treatment of syphilis in pregnant women prevent serious adverse outcomes such as **congenital syphilis**, which can cause severe fetal morbidity and mortality. *Urine analysis for bacteriuria* - **Urine analysis** for **asymptomatic bacteriuria** is routinely recommended during pregnancy because untreated bacteriuria can lead to pyelonephritis, preterm labor, and low birth weight. - It is a simple, **cost-effective** test with significant benefits for maternal and fetal health.
Question 2: Which is the best marker for NTD?
- A. Inhibin-A
- B. hCG
- C. Pseudocholinesterase
- D. AFP (Correct Answer)
Explanation: ***AFP*** - **Alpha-fetoprotein (AFP)** is the primary and most widely used biochemical marker for detecting **neural tube defects (NTDs)** during pregnancy. - Elevated levels of **AFP in maternal serum** or amniotic fluid are indicative of an open NTD, such as **spina bifida** or **anencephaly**, where fetal blood leaks into the amniotic fluid. *Inhibin-A* - **Inhibin-A** is typically used in the **quad screen** as a marker for **Down syndrome (Trisomy 21)**, where its levels are typically elevated. - It does not serve as a primary marker for the detection of neural tube defects. *hCG* - **Human Chorionic Gonadotropin (hCG)** is elevated in **Down syndrome** and decreased in **Edwards syndrome (Trisomy 18)** screening. - It is not a reliable marker for the diagnosis of neural tube defects. *Pseudocholinesterase* - **Pseudocholinesterase**, also known as butyrylcholinesterase, is a serum enzyme that can be **elevated in amniotic fluid** in cases of open NTDs. - While it can be a useful confirmatory test, its general utility as a primary marker is less than AFP, as it is less specific and more difficult to implement in routine screening.
Question 3: Which diagnostic tool is preferred for metabolic disease screening in children?
- A. Urinalysis
- B. Genetic testing
- C. Complete Blood count
- D. Tandem mass spectrometry (Correct Answer)
- E. Plasma amino acid analysis
Explanation: ***Tandem mass spectrometry*** - **Tandem mass spectrometry (TMS)** is the preferred method for newborn screening of many **inborn errors of metabolism** because it can simultaneously detect a wide range of metabolites from a single dried blood spot. - This technique rapidly identifies multiple **amino acid disorders**, **fatty acid oxidation disorders**, and **organic acidemias**, allowing for early intervention. *Urinalysis* - While urinalysis can detect some metabolic abnormalities (e.g., **ketones**, **glucose**), it is not a comprehensive screening tool for the broad spectrum of inherited metabolic diseases. - It primarily identifies end-products of metabolism rather than specific enzyme deficiencies or precursor compounds. *Genetic testing* - **Genetic testing** is highly specific for known genetic mutations, but it is typically used for confirmatory diagnosis or targeted screening when a specific condition is suspected, not for broad, universal newborn metabolic screening. - It can be expensive and time-consuming for population-wide screening of hundreds of potential metabolic disorders. *Complete Blood count* - A **complete blood count (CBC)** assesses cellular components of the blood (e.g., **red blood cells**, **white blood cells**, **platelets**) and is useful for detecting hematological disorders. - It does not directly screen for metabolic diseases, although some metabolic disorders can secondarily affect blood cell counts. *Plasma amino acid analysis* - **Plasma amino acid analysis** can detect specific aminoacidopathies (e.g., **phenylketonuria**, **maple syrup urine disease**), but it is limited to amino acid disorders only. - Unlike tandem mass spectrometry, it cannot simultaneously screen for fatty acid oxidation disorders and organic acidemias, making it less comprehensive for broad metabolic screening.
Question 4: Which of the following statements about chorionic villus sampling is false?
- A. Can cause limb deformities
- B. Is used for prenatal genetic diagnosis
- C. Villi are collected from chorion frondosum
- D. Is performed only in second trimester of pregnancy (Correct Answer)
Explanation: ***Is performed only in second trimester of pregnancy*** - This statement is false because **chorionic villus sampling (CVS)** is typically performed earlier in pregnancy, specifically during the **first trimester**, usually between 10 and 13 weeks of gestation. - Performing CVS only in the second trimester would negate one of its main advantages: providing earlier genetic diagnostic information than **amniocentesis**. *Is used for prenatal genetic diagnosis* - **CVS** is a primary method for **prenatal genetic diagnosis**, allowing for the detection of chromosomal abnormalities and genetic disorders. - It involves analyzing fetal cells obtained from the **chorionic villi**. *Villi are collected from chorion frondosum* - The sample for **CVS** is indeed collected from the **chorion frondosum**, which is the fetal part of the placenta containing numerous chorionic villi. - These villi are genetically identical to the fetus, making them suitable for **genetic analysis**. *Can cause limb deformities* - There is a recognized, albeit small, risk of **limb reduction defects** associated with CVS, particularly if performed very early in gestation (before 9-10 weeks). - This risk is part of the counseling provided to prospective parents considering the procedure.
Question 5: A newborn presents with metabolic acidosis, high ammonia, and orotic acid in urine. Which enzyme deficiency is most likely?
- A. Arginase
- B. Glutamine synthetase
- C. Ornithine transcarbamylase (Correct Answer)
- D. CPS-1
Explanation: ***Ornithine transcarbamylase*** - Deficiency of **ornithine transcarbamylase (OTC)**, a key enzyme in the urea cycle, leads to the accumulation of **carbamoyl phosphate**. - **Carbamoyl phosphate** is then shunted to the pyrimidine synthesis pathway, leading to increased production and excretion of **orotic acid** in the urine, along with **hyperammonemia** and **metabolic acidosis**. *Arginase* - **Arginase deficiency** in the urea cycle primarily causes increased **arginine levels** and **hyperammonemia**, but it does not typically lead to the accumulation of orotic acid. - The effects are often more chronic with gradual onset of symptoms, rather than severe neonatal presentation with orotic aciduria. *Glutamine synthetase* - **Glutamine synthetase** catalyzes the synthesis of glutamine from glutamate and ammonia, playing a crucial role in **ammonia detoxification**. - A deficiency would impair ammonia detoxification and lead to **hyperammonemia**, but it would not directly cause **orotic aciduria**. *CPS-1* - **Carbamoyl phosphate synthetase I (CPS-1)** deficiency is the first step of the urea cycle and leads to severe **hyperammonemia** due to the inability to form carbamoyl phosphate. - Unlike OTC deficiency, **CPS-1 deficiency** does not involve the buildup of carbamoyl phosphate; hence, **orotic acid levels** would be low or normal, not high.
Question 6: A 5 year old child was brought to the physician with a history of black urine. There is no history of fever or any other complaints. There is no growth retardation and all the developmental milestones are normal. The child is suspected to have an enzyme defect for metabolism of an aromatic amino acid. What is the enzyme deficient
- A. Homogentisate dehydrogenase
- B. Homogentistae oxidase (Correct Answer)
- C. Tyrosine Transaminase
- D. Tryptophan Hydroxylase
- E. Phenylalanine Hydroxylase
Explanation: ***Homogentistae oxidase*** - The presentation of a child with **black urine** (alkaptonuria) in the absence of other symptoms is characteristic of a deficiency in **homogentisate oxidase**. - This enzyme is crucial in the catabolism of **tyrosine**, and its deficiency leads to the accumulation of **homogentisic acid**, which oxidizes upon exposure to air, turning urine black. *Homogentisate dehydrogenase* - This enzyme is not a recognized component of the **tyrosine degradation pathway** in humans. - The correct enzyme involved in the breakdown of **homogentisate** is an oxidase, not a dehydrogenase, in this context. *Tyrosine Transaminase* - A deficiency in **tyrosine transaminase** (tyrosinemia type II) would lead to elevated tyrosine levels and typically presents with symptoms affecting the eyes, skin, and intellectual disability, not primarily black urine. - This condition is characterized by **ocular findings** (corneal ulcers), **skin lesions**, and **neurological symptoms**. *Tryptophan Hydroxylase* - This enzyme is involved in the synthesis of **serotonin** and **melatonin** from tryptophan, a different amino acid pathway. - A deficiency or abnormality in **tryptophan hydroxylase** would not cause black urine but could lead to neurological or mood disorders. *Phenylalanine Hydroxylase* - A deficiency in **phenylalanine hydroxylase** causes **phenylketonuria (PKU)**, which affects phenylalanine metabolism, not tyrosine metabolism directly. - PKU typically presents with **intellectual disability**, **musty odor**, **fair skin**, and **seizures** if untreated, not black urine.
Question 7: Which of the following techniques is used for the detection of variations in DNA sequence and gene expression?
- A. Southern blot
- B. Western blot
- C. Microarray (Correct Answer)
- D. Northern blot
Explanation: ***Microarray*** - **Microarrays** are designed to detect thousands of DNA or RNA sequences simultaneously, making them ideal for analyzing **gene expression profiles** and identifying **sequence variations** like SNPs. - They involve hybridizing labeled sample DNA/RNA to probes fixed on a solid surface, with the intensity of hybridization indicating the presence or abundance of specific sequences. *Northern blot* - The **Northern blot** technique is primarily used to study **gene expression** by detecting specific **RNA sequences** in a sample. - It does not directly analyze DNA sequence variations. *Southern blot* - The **Southern blot** is a molecular biology method used to detect specific **DNA sequences** in DNA samples. - While it can identify large-scale DNA rearrangements or deletions, it is not optimized for simultaneous detection of multiple gene expression levels or subtle sequence variations. *Western blot* - The **Western blot** is used to detect specific **proteins** in a sample. - It analyzes protein expression levels and modifications and is not designed for the detection of DNA sequence variations or gene expression at the RNA level.
Question 8: What is the name of the treatment for type I tyrosinemia?
- A. No treatment
- B. Vitamin B complex
- C. Nitisinone (Correct Answer)
- D. Symptomatic treatment only
Explanation: ***Nitisinone*** - **Nitisinone** (NTBC) is the primary treatment for **tyrosinemia type I**, an inherited metabolic disorder. - It works by inhibiting **4-hydroxyphenylpyruvate dioxygenase**, an enzyme upstream in the tyrosine degradation pathway, preventing the formation of toxic metabolites. *No treatment* - Leaving **tyrosinemia type I** untreated leads to severe complications such as **liver failure**, **renal tubular dysfunction**, and **neurological crises**. - Without intervention, the disease is often **fatal** in infancy or early childhood. *Symptomatic treatment only* - While supportive care is important, **symptomatic treatment alone** is insufficient to prevent the progressive and severe organ damage associated with tyrosinemia type I. - The underlying metabolic defect producing toxic metabolites must be addressed directly to achieve positive outcomes. *Vitamin B complex* - **Vitamin B complex** is not an effective treatment for type I tyrosinemia. - While certain inborn errors of metabolism respond to specific vitamin cofactors, **tyrosinemia type I** requires specific inhibition of a metabolic pathway, which vitamins cannot provide.
Question 9: Increasing severity of intellectual disability of male members over generations is a result of ?
- A. Y linked disorder
- B. Frameshift mutation
- C. Trinucleotide repeat mutation (Correct Answer)
- D. Mitochondrial DNA mutation
Explanation: ***Trinucleotide repeat mutation*** - This phenomenon, known as **anticipation**, is characteristic of disorders caused by trinucleotide repeat expansions like **Fragile X syndrome**, where the number of repeats increases in successive generations, leading to earlier onset and more severe symptoms. - The expansion of these repeats often occurs during **meiosis**, particularly **oogenesis** for Fragile X, contributing to the increasing severity observed in offspring. *Y linked disorder* - Y-linked disorders affect only males and are passed from father to son, but they do not typically show increasing severity over generations or the phenomenon of anticipation. - Their inheritance pattern is straightforward and generally consistent across generations, without progressive phenotypic changes. *Frameshift mutation* - A **frameshift mutation** involves the insertion or deletion of nucleotides that are not multiples of three, leading to a shift in the reading frame and an altered protein sequence. - While they can cause severe genetic disorders, **frameshift mutations** do not typically explain the observed increase in severity across generations (anticipation). *Mitochondrial DNA mutation* - Mitochondria are inherited exclusively from the mother, and mutations in **mitochondrial DNA** can cause a range of disorders affecting energy production. - While these disorders can vary in severity due to **heteroplasmy**, they do not typically show a pattern of increasing severity in successive generations due to an expanding repeat sequence.
Question 10: Which of the following is a sex-linked disorder?
- A. Hemophilia (Correct Answer)
- B. Neurofibromatosis
- C. Klinefelter's syndrome
- D. Thalassemia
Explanation: ***Hemophilia*** - Hemophilia is an **X-linked recessive disorder**, meaning the gene responsible is located on the X chromosome. - Males are predominantly affected because they have only one X chromosome, so a single copy of the mutated gene is sufficient to cause the disease. *Neurofibromatosis* - Neurofibromatosis is an **autosomal dominant disorder**, meaning a single copy of the mutated gene on a non-sex chromosome is enough to cause the condition. - It affects males and females equally and is characterized by tumors along nerves and skin changes. *Klinefelter's syndrome* - Klinefelter's syndrome is a **chromosomal disorder** resulting from an extra X chromosome in males (XXY), not a single gene mutation on a sex chromosome. - While it involves sex chromosomes, it's categorized as a **sex chromosome aneuploidy** rather than a sex-linked disorder in the traditional genetic sense. *Thalassemia* - Thalassemia is an **autosomal recessive disorder**, meaning it requires two copies of the mutated gene (one from each parent) on non-sex chromosomes to manifest. - It affects the production of hemoglobin and impacts males and females equally.
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