NEET-PG 2025 - Biochemistry Practice Questions

Q: A child presents with developmental delay and coarse facial features. Enzyme assay reveals a deficiency of α-L-iduronidase. Which of the following substances is most likely to accumulate in this condition?

Dermatan sulfate + Heparan sulfate. ***Dermatan sulfate + Heparan sulfate*** - The presenting features of developmental delay and **coarse facial features** point towards a Mucopolysaccharidosis (MPS). - A deficiency of **α-L-iduronidase** is diagnostic of **MPS Type I (Hurler syndrome)**, which leads to the accumulation of **Dermatan sulfate** and **Heparan sulfate**. *Dermatan sulfate + Chondroitin sulfate* - While **Dermatan sulfate** accumulates in MPS I, **Chondroitin sulfate** accumulation is characteristic of **MPS IV (Morquio syndrome)**, which has different clinical features (skeletal dysplasia, normal intelligence). - This combination does not correctly represent the primary storage products of **MPS I**. *Only Dermatan sulfate* - Both **MPS I (Hurler syndrome)** and **MPS II (Hunter syndrome)** result in accumulation of **both Dermatan sulfate AND Heparan sulfate**, not dermatan sulfate alone. - Listing dermatan sulfate alone is incomplete and does not accurately reflect the biochemical defect in **α-L-iduronidase deficiency**. *Heparan sulfate + Chondroitin sulfate* - **Heparan sulfate** does accumulate in MPS I, but the co-accumulation is with **Dermatan sulfate**, not Chondroitin sulfate. - **Chondroitin sulfate** accumulation is characteristic of **MPS IV (Morquio syndrome)**, which involves different enzyme deficiencies.

Q: A 6-month-old infant presents with recurrent infections and failure to thrive. Laboratory investigations reveal a deficiency of adenosine deaminase (ADA). Which of the following immunodeficiency disorders is most likely associated?

Severe Combined Immunodeficiency (SCID). ***Severe Combined Immunodeficiency (SCID)*** - **Adenosine deaminase (ADA) deficiency** is a classic autosomal recessive cause of SCID, resulting in accumulation of toxic metabolites like **dATP**. - These toxic metabolites destroy both **T and B lymphocytes**, leading to profound lymphopenia and the severe clinical picture of recurrent infections and **failure to thrive**. *Hypogammaglobulinemia* - This term generally refers to primary **B-cell intrinsic defects** leading to reduced antibody levels (e.g., X-linked agammaglobulinemia or CVID). - While it causes recurrent infections, the underlying genetic defect is specific to B-cell development or function, not **ADA deficiency** affecting both T and B cells profoundly. *DiGeorge Syndrome* - This syndrome is caused by a defect in the 3rd and 4th pharyngeal pouches, often due to **22q11 microdeletion**, resulting in **thymic aplasia** (T-cell deficiency). - Clinical presentation involves the triad of T-cell defect, **cardiac anomalies** (conotruncal defects), and **hypocalcemia** (parathyroid hypoplasia), not ADA deficiency. *Wiskott-Aldrich Syndrome* - This is an X-linked disorder defined by the classic triad of **eczema**, immunodeficiency, and **thrombocytopenia** (small platelets). - The mutation affects the **WASP gene**, leading to defective cytoskeleton function in hematopoietic cells, which is unrelated to ADA enzymatic deficiency.

Q: The pedigree diagram of a family is shown below. Affected individuals present with progressive external ophthalmoplegia, pigmentary retinopathy, and cardiac conduction defects. Based on the pedigree and clinical features, what is the most likely diagnosis?

Kearns-Sayre Syndrome. ***Kearns-Sayre Syndrome*** * Kearns-Sayre Syndrome (KSS) is a **mitochondrial disorder** caused by large-scale deletions in **mtDNA** (mtDNA deletion syndrome). * The classic triad of KSS is **progressive external ophthalmoplegia (PEO)**, **pigmentary retinopathy**, and onset before age 20, often associated with **cardiac conduction defects** and cerebellar ataxia, matching the clinical presentation. *Duchenne Muscular Dystrophy* * DMD is an **X-linked recessive** disorder, which would show mother-to-son transmission, but not father-to-son transmission. The pedigree shows affected males having affected children (both male and female), inconsistent with X-linked inheritance. * The primary features are **progressive proximal muscle weakness** and Gower's sign, not the characteristic ophthalmoplegia, retinopathy, and heart block of KSS. *Friedreich Ataxia* * Friedreich ataxia is an **autosomal recessive** disorder, which would typically skip generations and mainly present in siblings of unaffected parents. This is inconsistent with the clear mother-to-child transmission seen in the pedigree. * The key features are **ataxia**, **dysarthria**, and **loss of vibratory sense**, not primarily ophthalmoplegia and pigmentary retinopathy. *Myotonic Dystrophy* * Myotonic dystrophy (DM1) is an **autosomal dominant** disorder, consistent with the vertical transmission, but the genetic defect is an **unstable trinucleotide repeat (CTG)**. While it can involve **cardiac conduction defects**, the primary clinical feature is **myotonia** (inability to quickly relax muscles) and facial weakness. * The absence of myotonia and the distinct presentation of PEO and pigmentary retinopathy make KSS a better fit than myotonic dystrophy.

Question 1

A child presents with developmental delay and coarse facial features. Enzyme assay reveals a deficiency of α-L-iduronidase. Which of the following substances is most likely to accumulate in this condition?

Accepted Answer

Dermatan sulfate + Heparan sulfate

Answer

Only Dermatan sulfate

Answer

Heparan sulfate + Chondroitin sulfate

Answer

Dermatan sulfate + Chondroitin sulfate

Question 2

A 6-month-old infant presents with recurrent infections and failure to thrive. Laboratory investigations reveal a deficiency of adenosine deaminase (ADA). Which of the following immunodeficiency disorders is most likely associated?

Accepted Answer

Severe Combined Immunodeficiency (SCID)

Answer

Hypogammaglobulinemia

Answer

Wiskott-Aldrich Syndrome

Answer

DiGeorge Syndrome

Question 3

The pedigree diagram of a family is shown below. Affected individuals present with progressive external ophthalmoplegia, pigmentary retinopathy, and cardiac conduction defects. Based on the pedigree and clinical features, what is the most likely diagnosis?

Accepted Answer

Kearns-Sayre Syndrome

Answer

Duchenne Muscular Dystrophy

Answer

Friedreich Ataxia

Answer

Myotonic Dystrophy

NEET-PG 2025 — Biochemistry