Genetic Disorders and Biochemical Pathology Practice Questions

Q: What is the treatment for multiple carboxylase deficiency?

Biotin. **Explanation:** **Multiple Carboxylase Deficiency (MCD)** is a metabolic disorder caused by a defect in the metabolism of **Biotin (Vitamin B7)**. Biotin acts as a vital coenzyme for four major carboxylase enzymes: Pyruvate carboxylase, Acetyl-CoA carboxylase, Propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase. The correct answer is **Biotin** because MCD typically results from deficiencies in either **Holocarboxylase synthetase** (neonatal onset) or **Biotinidase** (late-onset). Holocarboxylase synthetase is required to attach biotin to the apoenzymes, while biotinidase is necessary to recycle biotin from dietary sources or protein turnover. Supplementation with pharmacological doses of free biotin bypasses these enzymatic blocks, restoring carboxylase activity and resolving clinical symptoms like dermatitis, alopecia, and metabolic acidosis. **Why incorrect options are wrong:** * **Pyridoxine (B6):** Used for Homocystinuria, Sideroblastic anemia, and B6-dependent seizures. It is a cofactor for transamination and decarboxylation, not carboxylation. * **Thiamine (B1):** Used for Beriberi, Wernicke-Korsakoff syndrome, and Maple Syrup Urine Disease (MSUD). It is a cofactor for oxidative decarboxylation (e.g., Pyruvate dehydrogenase). * **Folic acid (B9):** Used for Megaloblastic anemia and neural tube defect prevention. It is involved in one-carbon metabolism. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Triad:** Alopecia, skin rash (periorificial), and metabolic acidosis/organic aciduria. * **Biotinidase Deficiency:** Often presents later in infancy with neurological symptoms (seizures, hypotonia, hearing loss). * **Diagnosis:** Confirmed by measuring enzyme activity in leukocytes or fibroblasts and organic acid analysis in urine (showing 3-hydroxyisovaleric acid).

Q: A 44-year-old female presented with bony pain. On general examination, hepatosplenomegaly was observed. Biopsy from the spleen shows a crumpled tissue paper appearance. Which of the following products is likely to have accumulated?

Glucocerebroside. ### Explanation The clinical presentation of bony pain, hepatosplenomegaly, and the pathognomonic histological finding of **"crumpled tissue paper"** appearance in the spleen points directly to **Gaucher Disease**. **1. Why Glucocerebroside is Correct:** Gaucher disease is the most common lysosomal storage disorder, caused by a deficiency of the enzyme **Glucocerebrosidase** (Acid $\beta$-glucosidase). This deficiency leads to the accumulation of **Glucocerebroside** within the lysosomes of macrophages. These lipid-laden macrophages are called "Gaucher cells." Under the microscope, their cytoplasm appears fibrillar and wrinkled, resembling crumpled tissue paper or crumpled silk. These cells infiltrate the bone marrow (causing pain and Erlenmeyer flask deformity), spleen, and liver. **2. Why Other Options are Incorrect:** * **Ganglioside (GM2):** Accumulates in **Tay-Sachs Disease**. It presents with a cherry-red spot on the macula and neurodegeneration but lacks hepatosplenomegaly. * **Sphingomyelin:** Accumulates in **Niemann-Pick Disease**. While it features hepatosplenomegaly, the histology shows "foam cells" (vacuolated appearance) rather than crumpled tissue paper. * **Sulfatides:** Accumulate in **Metachromatic Leukodystrophy** due to Arylsulfatase A deficiency, leading to central and peripheral demyelination. **3. High-Yield Clinical Pearls for NEET-PG:** * **Enzyme Deficient:** Glucocerebrosidase. * **Radiological Sign:** **Erlenmeyer flask deformity** of the distal femur. * **Biochemical Marker:** Elevated serum **Chitotriosidase** and Tartrate-resistant acid phosphatase (TRAP). * **Treatment:** Enzyme Replacement Therapy (ERT) with Recombinant Glucocerebrosidase (Imiglucerase). * **Inheritance:** Autosomal Recessive.

Q: Oral contraceptive pills (OCPs) intake can cause psychiatric symptoms and abdominal pain. What is the most likely diagnosis associated with these symptoms?

Acute intermittent porphyria. **Explanation:** **Acute Intermittent Porphyria (AIP)** is the correct diagnosis. AIP is an autosomal dominant metabolic disorder caused by a deficiency of the enzyme **Porphobilinogen (PBG) deaminase**. The clinical hallmark of AIP is the "classic triad": abdominal pain, neuropsychiatric symptoms (anxiety, psychosis), and peripheral neuropathy. **Why OCPs trigger AIP:** Oral contraceptive pills contain progesterone, which induces the enzyme **ALA synthase (ALAS1)** in the liver. This induction leads to an accumulation of toxic heme precursors, specifically **delta-aminolevulinic acid (ALA)** and **porphobilinogen (PBG)**. These precursors are neurotoxic, precipitating acute attacks of abdominal pain and psychiatric distress. **Analysis of Incorrect Options:** * **B. Systemic Lupus Erythematosus (SLE):** While OCPs can exacerbate SLE, the primary presentation involves malar rash, joint pain, and photosensitivity rather than acute, drug-induced neuro-abdominal crises. * **C. Thrombosis:** OCPs are a major risk factor for Venous Thromboembolism (VTE) due to increased clotting factors, but this presents with limb swelling or pulmonary embolism, not psychiatric symptoms. * **D. Anemia:** OCPs actually reduce menstrual blood loss and are often used to *treat* iron-deficiency anemia. **High-Yield Clinical Pearls for NEET-PG:** * **Enzyme Deficient:** PBG Deaminase (also known as HMB Synthase). * **Accumulated Products:** ALA and PBG (detected in urine). * **Urine Finding:** Urine turns **"port-wine"** color on standing due to oxidation of PBG to porphobilin. * **Triggers:** Drugs (Barbiturates, Sulfonamides, OCPs), Alcohol, and Fasting (starvation). * **Treatment:** Intravenous **Hematin/Hemin** (inhibits ALA synthase via negative feedback) and high-glucose infusion.

Q: What is the total number of chromosomes in a patient with Turner syndrome?

45. **Explanation:** **Turner Syndrome** is a chromosomal disorder characterized by **monosomy of the X chromosome**. In a typical human cell, there are 46 chromosomes (23 pairs). In Turner syndrome, one of the sex chromosomes is missing, resulting in a **45,X** karyotype. Therefore, the total number of chromosomes is **45**. This is the only monosomy compatible with life in humans. **Analysis of Options:** * **Option A (45):** Correct. This represents the 44 autosomes plus a single X chromosome (45,X). * **Option B (47):** Incorrect. This represents **trisomy**. Common examples include Down syndrome (Trisomy 21), Klinefelter syndrome (47,XXY), or Patau syndrome (Trisomy 13). * **Option C (46):** Incorrect. This is the **euploid** (normal) number of chromosomes in humans (46,XX or 46,XY). * **Option D (42):** Incorrect. This number does not correspond to any common clinical chromosomal syndrome. **High-Yield Clinical Pearls for NEET-PG:** * **Karyotype:** 45,X is the most common (50%), but mosaicism (e.g., 45,X/46,XX) and structural abnormalities (e.g., Isochromosome Xq) also occur. * **Clinical Features:** Short stature (most common), **streak ovaries** (leading to primary amenorrhea and infertility), webbed neck (cystic hygroma), and widely spaced nipples (shield chest). * **Cardiovascular:** Bicuspid aortic valve (most common) and **Coarctation of the aorta**. * **Renal:** Horseshoe kidney. * **Biochemical Marker:** Elevated LH and FSH levels due to hypergonadotropic hypogonadism (lack of feedback inhibition from estrogen).

Q: A defect in the MRP2 transporter leads to which of the following conditions?

Dubin Johnson syndrome. **Explanation:** **Dubin-Johnson Syndrome (DJS)** is an autosomal recessive disorder characterized by conjugated hyperbilirubinemia. The underlying defect lies in the **MRP2 (Multidrug Resistance-associated Protein 2)** gene, also known as **ABCC2**. This protein is an ATP-dependent canalicular transporter responsible for the efflux of conjugated bilirubin from hepatocytes into the bile canaliculi. When MRP2 is defective, conjugated bilirubin leaks back into the blood, and a dark pigment (metabolites of epinephrine) accumulates in the lysosomes, giving the liver a characteristic **"black" appearance** on biopsy. **Analysis of Incorrect Options:** * **Menke’s Disease:** Caused by a defect in the **ATP7A** gene, leading to impaired copper absorption and transport. It is characterized by "kinky" hair and neurological degeneration. * **Familial Intrahepatic Cholestasis (PFIC):** These are a group of disorders involving different transporters. For example, PFIC1 involves **ATP8B1**, and PFIC2 involves the Bile Salt Export Pump (**BSEP/ABCB11**). * **Benign Recurrent Intrahepatic Cholestasis (BRIC):** This is a milder, episodic version of cholestasis often linked to mutations in the same genes as PFIC1 (ATP8B1). **High-Yield Clinical Pearls for NEET-PG:** * **DJS vs. Rotor Syndrome:** Both present with conjugated hyperbilirubinemia, but **Rotor Syndrome** lacks the black liver pigmentation and is caused by defects in OATP1B1 and OATP1B3 transporters. * **Urinary Coproporphyrin:** In DJS, total urinary coproporphyrin levels are normal, but **>80% is Coproporphyrin I** (normally, Coproporphyrin III predominates). * **Oral Cholecystography:** The gallbladder is typically **not visualized** in Dubin-Johnson Syndrome due to the transport defect.

Q: Niemann-Pick disease is inherited in which pattern?

Autosomal recessive. **Explanation:** **Niemann-Pick Disease (NPD)** is a lysosomal storage disorder characterized by the deficient activity of the enzyme **acid sphingomyelinase (ASM)** or defects in cholesterol trafficking (NPC1/NPC2). It follows an **Autosomal Recessive (AR)** inheritance pattern. This means an affected individual must inherit two mutated alleles (one from each carrier parent) to manifest the disease. Most enzyme deficiency disorders in biochemistry, particularly sphingolipidoses, follow this pattern. **Analysis of Options:** * **Autosomal Dominant (B):** This pattern usually involves structural protein defects (e.g., Marfan syndrome) or receptors (e.g., Familial Hypercholesterolemia). Metabolic enzyme deficiencies are rarely dominant because 50% enzyme activity in a heterozygote is typically sufficient for normal function. * **X-linked (C):** While some storage diseases like **Fabry disease** and **Hunter syndrome** are X-linked recessive, Niemann-Pick is not. * **Mitochondrial (D):** These are inherited exclusively from the mother and typically affect high-energy tissues (e.g., MELAS). NPD is caused by nuclear DNA mutations. **High-Yield Clinical Pearls for NEET-PG:** * **Biochemical Defect:** Accumulation of **sphingomyelin** in reticuloendothelial cells. * **Histology:** Pathognomonic **"Foam cells"** (lipid-laden macrophages) are seen in the bone marrow and tissues. * **Clinical Triad:** Hepatosplenomegaly, progressive neurodegeneration, and a **Cherry-red spot** on the macula (shared with Tay-Sachs, but Tay-Sachs lacks organomegaly). * **Type C:** Unlike Types A and B, Type C is due to a defect in **cholesterol transport** (NPC1/NPC2 genes), not a primary sphingomyelinase deficiency.

Q: Which of the following karyotypes is characteristic of Turner syndrome?

45XO. **Explanation:** **Turner Syndrome (45,XO)** is a chromosomal disorder characterized by complete or partial monosomy of the X chromosome in females. It is the most common sex chromosome abnormality in females, occurring in approximately 1 in 2,500 live births. **Why 45,XO is Correct:** The normal human karyotype consists of 46 chromosomes (23 pairs). In Turner syndrome, a nondisjunction event (usually during paternal meiosis) results in a zygote with only one functional X chromosome. The notation **45,XO** (or 45,X) signifies a total of 45 chromosomes with a single X sex chromosome and no second sex chromosome (O denotes the absence). **Analysis of Incorrect Options:** * **46,XO:** This is a nomenclatural error. A "46" count implies a full set of chromosomes; if an X is missing, the count must be 45. * **47,XXX (Triple X Syndrome):** This represents a trisomy of the X chromosome. These individuals are phenotypically female and often asymptomatic, though they may have tall stature or learning disabilities. * **Trisomy 21 (Down Syndrome):** This is an autosomal trisomy (47,XX+21 or 47,XY+21) involving chromosome 21, not a sex chromosome monosomy. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Features:** Short stature (most common), **webbed neck** (cystic hygroma remnant), **streak ovaries** (leading to primary amenorrhea and infertility), and a broad "shield" chest. * **Cardiovascular:** **Bicuspid aortic valve** (most common) and **Coarctation of the aorta**. * **Renal:** Horseshoe kidney. * **Biochemical Marker:** Elevated LH and FSH levels due to hypergonadotropic hypogonadism (lack of feedback inhibition from estrogen). * **Genetics:** 50% are 45,X; others are mosaics (e.g., 45,X/46,XX) or have structural abnormalities of the X chromosome.

Question 1

What is the treatment for multiple carboxylase deficiency?

Accepted Answer

Biotin

Answer

Pyridoxine

Answer

Thiamine

Answer

Folic acid

Question 2

A 44-year-old female presented with bony pain. On general examination, hepatosplenomegaly was observed. Biopsy from the spleen shows a crumpled tissue paper appearance. Which of the following products is likely to have accumulated?

Accepted Answer

Glucocerebroside

Answer

Ganglioside

Answer

Sphingomyelin

Answer

Sulfatides

Question 3

A baby presents with refusal to feed, skin lesions, seizures, and ketosis with organic acids in urine but normal ammonia levels. What is the likely diagnosis?

Accepted Answer

Multiple carboxylase deficiency

Answer

Propionic aciduria

Answer

Maple syrup urine disease

Answer

Urea cycle enzyme deficiency

Question 4

Which of the following is true regarding X-linked recessive disorders?

Accepted Answer

Menkes disease is associated with copper metabolism.

Answer

Ehlers-Danlos syndrome (often called 'rubber man syndrome') is associated with collagen defects, not primarily lungs.

Answer

Alport syndrome is primarily associated with kidney, ear, and eye defects, not skin.

Answer

Marfan syndrome is a connective tissue disorder with multi-system involvement, including skeletal, ocular, and cardiovascular systems, not specifically 'MS'.

Question 5

Oral contraceptive pills (OCPs) intake can cause psychiatric symptoms and abdominal pain. What is the most likely diagnosis associated with these symptoms?

Accepted Answer

Acute intermittent porphyria

Answer

Systemic lupus erythematosus

Answer

Thrombosis

Answer

Anemia

Question 6

What is the total number of chromosomes in a patient with Turner syndrome?

Accepted Answer

45

Answer

47

Answer

46

Answer

42

Question 7

A defect in the MRP2 transporter leads to which of the following conditions?

Accepted Answer

Dubin Johnson syndrome

Answer

Menke's disease

Answer

Familial intrahepatic cholestasis

Answer

Benign recurrent intrahepatic cholestasis

Question 8

Niemann-Pick disease is inherited in which pattern?

Accepted Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

X-linked

Answer

Mitochondrial

Question 9

A 6-year-old child presents with black spots on sclera and ear. Urine examination reveals that after 30 minutes of collection, the colour of the urine sample had changed. What is the most probable enzyme deficiency the child is suffering from?

Accepted Answer

Homogentisic acid oxidase

Answer

Phenylalanine hydroxylase

Answer

Epimerase

Answer

Multiple carboxylase

Question 10

Which of the following karyotypes is characteristic of Turner syndrome?

Accepted Answer

45XO

Answer

46XO

Answer

47XXX

Answer

Trisomy 21

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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