Genetic Disorders and Biochemical Pathology Practice Questions

Q: A 9-year-old female child presented with polyuria, polydipsia, and metabolic acidosis. On slit lamp examination, crystal deposits are seen in the cornea. What is the diagnosis?

Cystinosis. ### Explanation **Correct Answer: B. Cystinosis** **Mechanism:** Cystinosis is an autosomal recessive lysosomal storage disorder caused by a mutation in the **CTNS gene**, which encodes **cystinosin**, a lysosomal membrane transporter. Defective transport leads to the accumulation of **cystine crystals** within lysosomes across various tissues. The clinical presentation in this case points to **Fanconi Syndrome** (polyuria, polydipsia, and metabolic acidosis due to proximal renal tubular dysfunction), which is the hallmark of infantile nephropathic cystinosis. The pathognomonic finding is the presence of **hexagonal cystine crystals in the cornea** on slit-lamp examination. --- ### Why the other options are incorrect: * **A. Cystinuria:** This is a defect in the renal tubular reabsorption of COLA amino acids (Cystine, Ornithine, Lysine, Arginine). It presents with **cystine stones (calculi)** in the urinary tract, not systemic crystal deposition or Fanconi syndrome. * **C. Cystathioninuria:** An autosomal recessive deficiency of cystathionase. It is generally considered a benign metabolic anomaly with no specific clinical symptoms like corneal crystals or polyuria. * **D. Homocystinuria:** Caused by cystathionine β-synthase deficiency. It presents with ectopia lentis (downward dislocation), intellectual disability, and thromboembolism, but **not** corneal crystal deposition. --- ### NEET-PG High-Yield Pearls: * **Diagnosis:** Confirmed by measuring **intracellular cystine levels** in polymorphonuclear leukocytes. * **Treatment:** **Cysteamine** (a cystine-depleting agent) is the drug of choice. * **Renal Pathology:** Cystinosis is the most common cause of inherited Fanconi Syndrome in children. * **Biochemical Note:** Do not confuse *Cystine* (dimer of cysteine) with *Cysteine* (monomer). In cystinosis, it is the dimer that accumulates.

Q: Development of pellagra-like skin lesions in carcinoid syndrome is primarily due to:

Inadequate conversion of tryptophan to niacin. ### Explanation **Underlying Medical Concept:** In a healthy individual, approximately **1% of dietary Tryptophan** is used to synthesize Serotonin (5-HT), while the majority is utilized for protein synthesis and the production of **Niacin (Vitamin B3)** via the Kynurenine pathway. In **Carcinoid Syndrome** (typically originating from neuroendocrine tumors of the midgut), the tumor cells become metabolically hyperactive. They divert up to **60% of the body's Tryptophan** into the synthesis of Serotonin. This massive "biochemical shift" creates a profound systemic deficiency of Tryptophan available for the Kynurenine pathway. Since Tryptophan is a precursor for Niacin, this diversion leads to secondary Niacin deficiency, manifesting clinically as **Pellagra** (Dermatitis, Diarrhea, Dementia). **Analysis of Options:** * **Option A (Correct):** The diversion of the precursor (Tryptophan) to the Serotonin pathway directly limits the endogenous synthesis of Niacin. * **Option B:** While the symptoms resemble dietary deficiency, the root cause in carcinoid syndrome is metabolic diversion, not a lack of intake. * **Option C:** The rash is not a direct effect of serotonin on the skin; it is a result of the underlying vitamin deficiency. * **Option D:** While carcinoid syndrome is a paraneoplastic process, the specific mechanism for the *pellagra-like lesions* is the biochemical depletion of Tryptophan. **High-Yield Clinical Pearls for NEET-PG:** * **The 60mg Rule:** 60 mg of Tryptophan yields 1 mg of Niacin. * **Diagnostic Marker:** Elevated urinary **5-HIAA** (5-Hydroxyindoleacetic acid), the breakdown product of serotonin. * **Other causes of Pellagra:** Hartnup disease (impaired Tryptophan absorption) and Isoniazid (INH) therapy (depletes Vitamin B6, a cofactor for Niacin synthesis). * **Classic Triad of Carcinoid:** Flushing, Diarrhea, and Right-sided heart failure (Tricuspid regurgitation).

Q: Hartnup disease can present with which of the following clinical features?

Pellagra-like symptoms. **Explanation:** **Hartnup disease** is an autosomal recessive disorder caused by a mutation in the **SLC6A19 gene**, which encodes a sodium-dependent neutral amino acid transporter. This defect leads to the impaired intestinal absorption and renal tubular reabsorption of neutral amino acids, most significantly **Tryptophan**. 1. **Why Option A is Correct:** Tryptophan is a vital precursor for the endogenous synthesis of **Niacin (Vitamin B3)**. In Hartnup disease, the deficiency of Tryptophan results in a secondary deficiency of Niacin. This manifests clinically as **Pellagra-like symptoms**, characterized by the "3 Ds": Dermatitis (photosensitive scaly rash), Diarrhea, and Dementia (ataxia and neurological symptoms). 2. **Why Other Options are Incorrect:** * **B. Nephrolithiasis:** This is characteristic of **Cystinuria**, where there is a defect in the transport of COAL (Cystine, Ornithine, Arginine, Lysine), leading to cystine stones. * **C. Protein intolerance:** This is typically seen in **Urea Cycle Disorders** (e.g., OTC deficiency), where protein ingestion leads to hyperammonemia. * **D. Microcephaly:** This is a common feature of **Maternal PKU** or certain TORCH infections, but not a primary feature of neutral amino acid transport defects. **Clinical Pearls for NEET-PG:** * **Diagnosis:** Confirmed by detecting **neutral aminoaciduria** (specifically Tryptophan) in the urine using paper chromatography. * **Treatment:** High-protein diet and **Nicotinamide (Niacin) supplementation**. * **Distinction:** Unlike dietary Pellagra, Hartnup disease will show high levels of neutral amino acids in the urine.

Q: Hunter syndrome is due to the deficiency of which enzyme?

Iduronate sulfatase. **Explanation:** **Hunter Syndrome (Mucopolysaccharidosis Type II)** is a lysosomal storage disorder characterized by the accumulation of glycosaminoglycans (GAGs), specifically **Dermatan sulfate and Heparan sulfate**. 1. **Why Option A is Correct:** Hunter syndrome is caused by a deficiency of the enzyme **Iduronate sulfatase**. This enzyme is responsible for the degradation of sulfated iduronic acid residues in GAGs. A unique high-yield feature of Hunter syndrome is its inheritance pattern: it is the **only X-linked recessive** Mucopolysaccharidosis (MPS); all others are autosomal recessive. 2. **Why Other Options are Incorrect:** * **Option B (Hexosaminidase A):** Deficiency leads to **Tay-Sachs disease**, a sphingolipidosis characterized by cherry-red spots on the macula and no hepatosplenomegaly. * **Option C (Glucocerebrosidase):** Deficiency causes **Gaucher disease**, the most common lysosomal storage disorder, presenting with "wrinkled paper" appearance of macrophages and bone involvement. * **Option D (α-L Iduronidase):** Deficiency leads to **Hurler syndrome (MPS I)**. While clinically similar to Hunter syndrome, Hurler syndrome is more severe, autosomal recessive, and uniquely presents with **corneal clouding**. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Hunter:** "The **Hunter** needs **X**-ray vision (X-linked) to see the **Target** (No corneal clouding)." * **Clinical Presentation:** Coarse facial features (gargoylism), hepatosplenomegaly, joint stiffness, and mental retardation. * **Diagnosis:** Increased urinary excretion of heparan and dermatan sulfate; confirmed by enzyme assay in leukocytes or fibroblasts.

Q: In Hartnup disease, which type of amino acids are primarily excreted into the urine?

Neutral amino acids. **Explanation:** **Hartnup disease** is an autosomal recessive disorder caused by a mutation in the **SLC6A19 gene**, which encodes a sodium-dependent **neutral amino acid transporter** located in the proximal renal tubules and the intestinal mucosa. 1. **Why Neutral Amino Acids are Correct:** The defective transporter is specific for neutral amino acids (e.g., Alanine, Valine, Threonine, and most importantly, **Tryptophan**). Because these amino acids cannot be reabsorbed in the kidneys, they are excreted in large amounts in the urine (**neutral aminoaciduria**). Similarly, impaired intestinal absorption leads to the bacterial breakdown of unabsorbed Tryptophan into indolic compounds, which are excreted in feces and urine. 2. **Why Other Options are Incorrect:** * **Basic Amino Acids (A):** Defective transport of basic amino acids (Lysine, Arginine, Ornithine) and Cystine is characteristic of **Cystinuria** (COLA mnemonic), not Hartnup disease. * **Acidic Amino Acids (B):** These (Glutamate, Aspartate) use different transport systems (e.g., EAAT) and are unaffected in this condition. * **Hydrophilic Amino Acids (D):** While some neutral amino acids are hydrophilic, this is too broad a category. The pathology specifically targets the "neutral" charge group. **NEET-PG High-Yield Clinical Pearls:** * **Pellagra-like symptoms:** Tryptophan is a precursor for **Niacin (Vitamin B3)**. Deficiency leads to the "3 Ds": Dermatitis (photosensitive), Diarrhea, and Dementia. * **Diagnosis:** Characterized by neutral aminoaciduria and the presence of **indican** in the urine (Obermayer test). * **Treatment:** High-protein diet and **Nicotinamide** supplementation.

Question 1

Which enzyme deficiency is most commonly responsible for the presence of a long clitoris and fused vagina?

Accepted Answer

21 hydroxylase

Answer

11 hydroxylase

Answer

3 beta hydroxy steroid dehydrogenase

Answer

None of the above

Question 2

A 9-year-old female child presented with polyuria, polydipsia, and metabolic acidosis. On slit lamp examination, crystal deposits are seen in the cornea. What is the diagnosis?

Accepted Answer

Cystinosis

Answer

Cystinuria

Answer

Cystothioninuria

Answer

Homocysteinuria

Question 3

A 25-year-old male presented with pigmentation of the nose and pinna. After voiding, his urine becomes dark. What spinal abnormality is most likely to be present?

Accepted Answer

Calcification of the disc

Answer

Atlantoaxial subluxation

Answer

Spondyloptosis

Answer

Basilar invagination

Question 4

All of the following are associated with non-ketotic hypoglycemia, EXCEPT?

Accepted Answer

Von Gierke's disease

Answer

Insulinoma

Answer

Carnitine deficiency

Answer

MCAD deficiency

Question 5

In a pregnant woman with elevated blood phenylalanine levels, her offspring is most likely to develop which of the following conditions?

Accepted Answer

Mental retardation

Answer

Lighter complexion

Answer

Microcephaly

Answer

Reduction of limb growth

Question 6

Lesch-Nyhan syndrome is associated with deficiency of which of the following?

Accepted Answer

Hypoxanthine-guanine phosphoribosyltransferase (total activity)

Answer

Hypoxanthine-guanine phosphoribosyltransferase (partial activity)

Answer

Phosphoribosyl pyrophosphate (partial activity)

Answer

Phosphoribosyl pyrophosphate (total activity)

Question 7

Development of pellagra-like skin lesions in carcinoid syndrome is primarily due to:

Accepted Answer

Inadequate conversion of tryptophan to niacin

Answer

Dietary niacin deficiency

Answer

Serotonin-induced skin rash mimicking pellagra

Answer

Paraneoplastic manifestation

Question 8

Hartnup disease can present with which of the following clinical features?

Accepted Answer

Pellagra-like symptoms

Answer

Nephrolithiasis

Answer

Protein intolerance

Answer

Microcephaly

Question 9

Hunter syndrome is due to the deficiency of which enzyme?

Accepted Answer

Iduronate sulfatase

Answer

Hexosaminidase

Answer

Glucocerebrosidase

Answer

a-L Iduronidase

Question 10

In Hartnup disease, which type of amino acids are primarily excreted into the urine?

Accepted Answer

Neutral amino acids

Answer

Basic amino acids

Answer

Acidic amino acids

Answer

Hydrophilic amino acids

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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