Genetic Disorders and Biochemical Pathology Practice Questions

Q: Which chromosomal compliment is associated with Turner syndrome?

Turner syndrome. **Explanation:** **Turner Syndrome (45, XO)** is the correct answer. It is a form of gonadal dysgenesis caused by the complete or partial absence of one X chromosome in females. This occurs most commonly due to **nondisjunction** during paternal meiosis. The lack of the second sex chromosome leads to the characteristic "streak ovaries" and a deficiency in estrogen. **Analysis of Incorrect Options:** * **Edward Syndrome (Trisomy 18):** This is an autosomal chromosomal disorder characterized by an extra copy of chromosome 18. Key features include "rocker-bottom" feet, micrognathia, and clenched fists with overlapping fingers. * **Patau Syndrome (Trisomy 13):** This involves an extra copy of chromosome 13. It presents with severe midline defects such as holoprosencephaly, cleft lip/palate, and polydactyly. * **Klinefelter Syndrome (47, XXY):** This is a male chromosomal disorder where there is at least one extra X chromosome. It presents with testicular atrophy, gynecomastia, and a tall, eunuchoid body habitus. **High-Yield Clinical Pearls for NEET-PG:** * **Most common cause of primary amenorrhea:** Turner Syndrome. * **Cardiovascular associations:** Bicuspid aortic valve (most common) and Coarctation of the aorta. * **Physical findings:** Webbed neck (cystic hygroma), short stature, and widely spaced nipples (shield chest). * **Renal anomaly:** Horseshoe kidney. * **Biochemical profile:** Elevated LH and FSH (Hypergonadotropic hypogonadism) due to lack of feedback inhibition from estrogen.

Q: Phenylketonuria is inherited in which pattern?

Autosomal recessive. **Explanation:** **Phenylketonuria (PKU)** is a classic example of an **Autosomal Recessive (AR)** disorder. It is primarily caused by a deficiency of the hepatic enzyme **Phenylalanine Hydroxylase (PAH)**, or less commonly, its cofactor **Tetrahydrobiopterin (BH4)**. In AR inheritance, an individual must inherit two mutated alleles (one from each carrier parent) to manifest the disease. This pattern is typical for most inborn errors of metabolism involving enzyme deficiencies, as a single functional gene (in heterozygotes) usually produces enough enzyme to maintain normal metabolic function. **Analysis of Incorrect Options:** * **Autosomal Dominant (AD):** These disorders typically involve structural proteins (e.g., Marfan syndrome) or receptors (e.g., Familial Hypercholesterolemia). A single mutant allele is sufficient to cause the phenotype. * **X-linked Dominant:** These are rare (e.g., Alport syndrome, Vitamin D-resistant rickets) and affect both males and females, often being more severe in males. * **X-linked Recessive:** These primarily affect males (e.g., Hemophilia, G6PD deficiency). PKU affects both sexes equally, ruling out X-linked inheritance. **High-Yield Clinical Pearls for NEET-PG:** * **Biochemical Hallmark:** Accumulation of Phenylalanine and its metabolites (Phenylpyruvate, Phenyllactate, Phenylacetate) in blood and urine. * **Clinical Presentation:** Intellectual disability, **"Mousy/Musty" body odor**, microcephaly, and hypopigmentation (due to decreased melanin synthesis). * **Diagnosis:** Guthrie Test (bacterial inhibition assay) or Tandem Mass Spectrometry (TMS) for newborn screening. * **Management:** Lifelong restriction of dietary Phenylalanine; Tyrosine becomes an **essential amino acid** for these patients.

Q: What is the triplet repeat sequence associated with Huntington's disease?

CAG. **Explanation:** **Huntington’s Disease (HD)** is an autosomal dominant neurodegenerative disorder characterized by the expansion of a trinucleotide repeat. The correct answer is **CAG** (Option C). This repeat occurs in the *HTT* gene on chromosome 4, which encodes the protein huntingtin. The **CAG** sequence codes for the amino acid **Glutamine**. Therefore, HD is classified as a **polyglutamine (polyQ) disease**. The expanded polyglutamine tract leads to a "gain-of-function" mutation where the mutant huntingtin protein aggregates, causing neuronal death, particularly in the caudate nucleus and putamen (striatum). **Analysis of Incorrect Options:** * **A. CTG:** Associated with **Myotonic Dystrophy** (Type 1). It affects the *DMPK* gene. (Mnemonic: **C**ataract, **T**oupee/Balding, **G**onadal atrophy). * **B. CGG:** Associated with **Fragile X Syndrome**. It occurs in the *FMR1* gene. (Mnemonic: **C**hin/Giant Gonads). * **D. GAA:** Associated with **Friedreich Ataxia**. It occurs in the *FXN* gene encoding frataxin. (Mnemonic: Friedreich is **GAA**y/Gait Ataxia Always). **High-Yield Clinical Pearls for NEET-PG:** * **Anticipation:** HD shows anticipation (earlier onset/increased severity in successive generations), typically when inherited from the **father** (paternal transmission). * **Threshold:** Normal repeats are 40 repeats are fully penetrant for the disease. * **Clinical Triad:** Chorea, Dementia, and Psychiatric symptoms (depression/aggression). * **Imaging:** "Boxcar ventricles" on MRI due to atrophy of the caudate nucleus.

Q: Which of the following is an X-linked recessive disorder?

Wiskott-Aldrich Syndrome. **Explanation:** **Wiskott-Aldrich Syndrome (WAS)** is the correct answer. It is an **X-linked recessive** primary immunodeficiency characterized by the triad of **thrombocytopenia** (with small platelets), **eczema**, and **recurrent infections**. It is caused by a mutation in the *WAS* gene, which encodes the Wiskott-Aldrich Syndrome Protein (WASP), essential for actin cytoskeleton reorganization in hematopoietic cells. **Analysis of Incorrect Options:** * **Rett Syndrome:** This is an **X-linked dominant** disorder. It primarily affects females because it is typically lethal in utero for males. It is characterized by regression of motor and language skills and purposeful hand-wringing movements. * **Thalassemia:** This is a group of **autosomal recessive** hemoglobinopathies. Both Alpha and Beta thalassemias require inheritance of defective alleles from both parents to manifest the major disease state. * **Alkaptonuria:** This is a classic **autosomal recessive** metabolic disorder caused by a deficiency of homogentisate oxidase. It leads to the accumulation of homogentisic acid, causing dark urine and ochronosis. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for X-linked Recessive:** "The **W**ise **G**iant **H**unter **D**ashed **B**riskly to **C**atch the **F**abry **L**ion" (**W**iskott-Aldrich, **G**6PD deficiency, **H**emophilia A/B, **D**uchenne/Becker MD, **B**ruton’s Agammaglobulinemia, **C**olor blindness, **F**abry disease, **L**esch-Nyhan). * **WAS Key Lab Finding:** Low IgM, high IgA, and high IgE levels, along with characteristically **small platelets** on a peripheral smear. * **Inheritance Pattern Tip:** Most enzyme deficiencies are Autosomal Recessive, while structural protein defects are often Autosomal Dominant. X-linked disorders are high-frequency topics in NEET-PG.

Q: SnRNA mutation is associated with which syndrome?

Prader Willi syndrome. **Explanation:** **Prader-Willi Syndrome (PWS)** is the correct answer because it is fundamentally linked to the loss of expression of paternal genes on chromosome **15q11-q13**. A critical component of this region is the **SNRPN gene**, which encodes the **Small Nuclear Ribonucleoprotein Polypeptide N**. This protein is essential for the formation of **snRNPs (snurps)**, which are the core components of the **spliceosome**. Mutations or deletions affecting these snRNAs disrupt the alternative splicing of pre-mRNA in the brain, particularly in the hypothalamus, leading to the clinical features of PWS. **Analysis of Incorrect Options:** * **Turner Syndrome (45, XO):** A chromosomal numerical abnormality (monosomy) characterized by short stature and streak ovaries; it is not caused by snRNA mutations. * **Klinefelter Syndrome (47, XXY):** A sex chromosome aneuploidy resulting in primary hypogonadism and gynaecomastia; it involves an extra X chromosome, not splicing machinery. * **Patau Syndrome (Trisomy 13):** A trisomy characterized by midline defects (cleft lip/palate, holoprosencephaly) and polydactyly; it is a chromosomal duplication disorder. **High-Yield Clinical Pearls for NEET-PG:** * **Genetics of PWS:** Most commonly due to **Paternal Deletion** (70%) or **Maternal Uniparental Disomy** (25%). * **Clinical Triad:** Infantile hypotonia, hyperphagia leading to early-onset obesity, and hypogonadism. * **Splicing Connection:** Remember that **snRNAs (U1, U2, U4, U5, U6)** are rich in uridine and are vital for removing introns. PWS is one of the few classic genetic disorders directly linked to a defect in the splicing apparatus components. * **Diagnostic Tool:** DNA methylation analysis is the gold standard for diagnosis.

Q: Which of the following is NOT a disorder due to peroxisomal abnormalities?

Jamaican vomiting sickness. **Explanation:** The correct answer is **Jamaican vomiting sickness** because it is a metabolic disorder caused by an acquired toxin, not a genetic peroxisomal defect. **1. Why Jamaican Vomiting Sickness is the correct answer:** Jamaican vomiting sickness is caused by the ingestion of **hypoglycin A**, a toxin found in the unripe fruit of the **Ackee tree**. This toxin inhibits the enzyme **Isovaleryl-CoA dehydrogenase** and interferes with **beta-oxidation of fatty acids**. This leads to profound hypoglycemia and the accumulation of organic acids. It is a mitochondrial/metabolic inhibition disorder, not a peroxisomal biogenesis or enzyme defect. **2. Why the other options are incorrect (Peroxisomal Disorders):** * **Zellweger Syndrome:** This is the most severe **peroxisomal biogenesis disorder (PBD)**. It is caused by mutations in *PEX* genes, leading to an inability to import proteins into peroxisomes, resulting in "empty" peroxisomes. * **Refsum’s Disease:** This is a peroxisomal enzyme deficiency. It is caused by a deficiency of **Phytanoyl-CoA hydroxylase**, the enzyme required for the **alpha-oxidation** of phytanic acid (a branched-chain fatty acid). * **Hyperoxaluria Type I:** This is caused by a deficiency of the peroxisomal enzyme **alanine-glyoxylate aminotransferase (AGT)**. This leads to the overproduction of oxalate, resulting in kidney stones and nephrocalcinosis. **High-Yield Clinical Pearls for NEET-PG:** * **Zellweger Syndrome:** Look for the triad of craniofacial dysmorphism, hypotonia ("floppy infant"), and hepatomegaly. * **Refsum’s Disease:** Key features include retinitis pigmentosa, peripheral neuropathy, and ataxia. Treatment involves a **diet low in chlorophyll** (phytanic acid source). * **Adrenoleukodystrophy (ALD):** Another high-yield peroxisomal disorder involving the accumulation of **Very Long Chain Fatty Acids (VLCFA)** due to a defective ABCD1 transporter.

Q: Which of the following conditions causes hyperuricemia due to both increased production and decreased excretion?

Glucose-6-phosphatase deficiency. **Explanation:** **Glucose-6-phosphatase deficiency (Von Gierke Disease/GSD Type I)** is the correct answer because it leads to hyperuricemia through a unique dual mechanism: 1. **Increased Production:** The deficiency of Glucose-6-phosphatase causes Glucose-6-phosphate (G6P) to accumulate. This excess G6P is diverted into the **Pentose Phosphate Pathway (PPP)**, leading to increased synthesis of Ribose-5-phosphate. This elevates **PRPP (Phosphoribosyl pyrophosphate)** levels, which drives de novo purine synthesis and subsequent degradation to uric acid. 2. **Decreased Excretion:** Impaired gluconeogenesis leads to chronic **Lactic Acidosis**. Lactic acid competes with uric acid for the same secretory transport mechanism in the renal tubules, thereby reducing the renal clearance of uric acid. **Analysis of Incorrect Options:** * **PRPP Synthetase overactivity:** Causes hyperuricemia solely due to **increased production** of purines via the de novo pathway. * **HGPRT deficiency (Lesch-Nyhan Syndrome):** Leads to hyperuricemia via **increased production** (failure of the salvage pathway increases PRPP levels and purine turnover). * **Renal failure:** Causes hyperuricemia solely due to **decreased excretion** (reduced glomerular filtration and tubular secretion). **High-Yield Clinical Pearls for NEET-PG:** * **Von Gierke Disease Presentation:** Characterized by "Doll-like" facies, massive hepatomegaly, fasting hypoglycemia, hyperlactatemia, hyperlipidemia, and hyperuricemia. * **The "Competition" Rule:** Remember that any condition causing high organic acids (Lactic acid, Ketoacids) will typically cause secondary hyperuricemia due to renal competition. * **Treatment Note:** Allopurinol is often used in GSD Type I to manage secondary gout.

Question 1

Which chromosomal compliment is associated with Turner syndrome?

Accepted Answer

Turner syndrome

Answer

Edward syndrome

Answer

Patau syndrome

Answer

Klinefelter syndrome

Question 2

Phenylketonuria is inherited in which pattern?

Accepted Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

X-linked dominant

Answer

X-linked recessive

Question 3

What is the triplet repeat sequence associated with Huntington's disease?

Accepted Answer

CAG

Answer

CTG

Answer

CGG

Answer

GAA

Question 4

Which of the following is an X-linked recessive disorder?

Accepted Answer

Wiskott-Aldrich Syndrome

Answer

Rett Syndrome

Answer

Thalassemia

Answer

Alkaptonuria

Question 5

SnRNA mutation is associated with which syndrome?

Accepted Answer

Prader Willi syndrome

Answer

Turner syndrome

Answer

Klinefelter syndrome

Answer

Patau syndrome

Question 6

Dubin Johnson syndrome is characterized by all of the following except?

Accepted Answer

Oral contraceptives are not contraindicated in this disease.

Answer

Defective bilirubin excretion into the bile.

Answer

Mutation in MRP-2.

Answer

Rifampicin may reduce MRP-2 function.

Question 7

Genetic deficiencies of NADPH oxidase cause which of the following conditions?

Accepted Answer

Chronic granulomatous diseases

Answer

Mitochondrial myopathies

Answer

Decreased ATP production

Answer

Lactic acidosis

Question 8

Which of the following is NOT a disorder due to peroxisomal abnormalities?

Accepted Answer

Jamaican vomiting sickness

Answer

Zellweger syndrome

Answer

Refsum's disease

Answer

Hyperoxaluria type I

Question 9

Lack of a specific lysosomal hydrolase for glycoproteins will most likely cause which of the following conditions?

Accepted Answer

Oligosaccharidoses

Answer

I cell disease

Answer

Scurvy

Answer

Ehlers-Danlos syndrome

Question 10

Which of the following conditions causes hyperuricemia due to both increased production and decreased excretion?

Accepted Answer

Glucose-6-phosphatase deficiency

Answer

PRPP Synthetase overactivity

Answer

Hereditary Gout (HGP) deficiency

Answer

Renal failure

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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