Genetic Disorders and Biochemical Pathology Practice Questions

Q: What is the metabolic defect in primary oxaluria type II?

D Glycerate dehydrogenase. ***D Glycerate dehydrogenase*** - Primary oxaluria type II (PH2) specifically results from a deficiency in the enzyme **D-glycerate dehydrogenase** (also known as glyoxylate reductase/hydroxypyruvate reductase). - This deficiency leads to the accumulation of **L-glyceric acid** and **oxalate**, causing kidney stones and kidney failure. *Glycine cleavage system* - Defects in the glycine cleavage system are associated with **nonketotic hyperglycinemia**, a condition involving high levels of glycine. - This defect does not primarily cause the accumulation of oxalate. *Alanine glyoxalate amino transferase* - A deficiency in **alanine-glyoxylate aminotransferase (AGT)** is the underlying defect in **primary oxaluria type I (PH1)**. - PH1 is the most common and severe form of primary hyperoxaluria, leading to increased oxalate production. *Excess vitamin C* - While **excessive vitamin C intake** can contribute to increased urinary oxalate excretion in some individuals, it is not a genetic metabolic defect. - It is an exogenous factor, not an intrinsic enzyme deficiency causing primary hyperoxaluria.

Q: Inheritance of Huntington's disease is

Autosomal Dominant. ***AD*** - Huntington's chorea is inherited in an **autosomal dominant** manner, meaning only one copy of the mutated gene is sufficient to cause the disorder [1]. - The disease typically manifests in mid-adulthood, with progressively worsening movement disorders and cognitive decline [1]. *XR* - X-linked recessive disorders typically affect **males** and can be transmitted by carrier females; this is not the case for Huntington's chorea. - The inheritance pattern does not align with the typical clinical presentation of Huntington's, which does not show a gender bias. *XD* - X-linked dominant disorders often affect both sexes, but their inheritance pattern does not describe Huntington's chorea. - Symptoms and gene affected are clearly linked with **autosomal dominant** inheritance, not X-linked dominant. *AR* - Autosomal recessive conditions typically require two copies of the mutated gene, which is not applicable to Huntington's chorea. - This pattern generally leads to earlier onset conditions and significantly different clinical presentations than those observed in Huntington's. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 149-150.

Q: Which one of the following disorders is not X-linked recessive?

Charcot-Marie-Tooth disease. **Charcot-Marie-Tooth disease** - Charcot-Marie-Tooth disease encompasses a group of **hereditary neuropathies** that are most commonly inherited in an **autosomal dominant** pattern, though autosomal recessive and X-linked forms exist, but the dominant form is the most prevalent. - Its diverse genetic basis means it's not exclusively an X-linked recessive disorder. *Lesch-Nyhan syndrome* - This is an **X-linked recessive** disorder caused by a deficiency of the enzyme **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)**. - It is characterized by **hyperuricemia**, neurological dysfunction, and self-mutilating behavior. *Hunter syndrome* - Hunter syndrome (Mucopolysaccharidosis Type II) is an **X-linked recessive** lysosomal storage disorder [1]. - It results from a deficiency of the enzyme **iduronate-2-sulfatase** [1]. *Fragile-X syndrome* - Fragile-X syndrome is an **X-linked disorder** and is the most common inherited cause of intellectual disability. - It is caused by an expansion of a **CGG trinucleotide repeat** in the FMR1 gene.

Q: Lysosomal transport defect is seen in which of the following conditions?

Cystinosis. ***Cystinosis*** - Cystinosis is characterized by **lysosomal transport defects** leading to the accumulation of cystine within lysosomes. - This condition results in **multisystemic involvement**, primarily affecting the kidneys and eyes, due to the inability to effectively transport cystine out of the lysosomes. *Metachromatic leukosytrophy* - Caused by deficiency of the **enzyme arylsulfatase A**, leading to sulfatide accumulation in lysosomes [1]. - It primarily affects the **nervous system** and is not primarily linked to a defect in lysosomal transport. *Goucher's disease* - Results from a deficiency of the enzyme **glucocerebrosidase**, leading to glucocerebroside accumulation [1]. - It mainly affects the **spleen, liver, and bone marrow**, rather than a generalized lysosomal transport defect. *Tay Sach's disease* - Caused by a deficiency in the **enzyme hexosaminidase A**, leading to GM2 ganglioside accumulation in neurones [1]. - This condition primarily affects the **nervous system** and does not involve a defect in lysosomal transport [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 159-164.

Q: Biochemical etiology of Alzheimer's disease relates to:

Acetylcholine. ***Acetylcholine*** - Alzheimer's disease is significantly associated with a **reduction in cholinergic neuronal activity** in the brain, impacting memory and learning. - Medications for Alzheimer's disease often aim to **increase acetylcholine levels** or prevent its breakdown (e.g., cholinesterase inhibitors). *Dopamine* - **Dopamine deficits** are primarily associated with **Parkinson's disease**, affecting motor control and movement. - While dopamine may play a minor role, it is **not considered the primary biochemical etiology** of Alzheimer's. *GABA* - **GABA (gamma-aminobutyric acid)** is the main inhibitory neurotransmitter in the brain and is often associated with anxiety disorders and epilepsy. - While GABAergic system changes can occur in Alzheimer's, they are **secondary to the primary cholinergic dysfunction**. *Serotonin* - **Serotonin** is widely known for its role in mood, sleep, and appetite regulation, and its imbalances are linked to depression and anxiety. - While some **serotonergic changes** can be observed in Alzheimer's disease, the primary biochemical deficit is not serotonin.

Question 1

What is the metabolic defect in primary oxaluria type II?

Accepted Answer

D Glycerate dehydrogenase

Answer

Glycine cleavage system

Answer

Alanine glyoxalate amino transferase

Answer

Excess vitamin C

Question 2

Inheritance of Huntington's disease is

Accepted Answer

Autosomal Dominant

Answer

X-Linked Recessive

Answer

Autosomal Recessive

Answer

X-Linked Dominant

Question 3

Which one of the following disorders is not X-linked recessive?

Accepted Answer

Charcot-Marie-Tooth disease

Answer

Lesch-Nyhan syndrome

Answer

Hunter syndrome

Answer

Fragile-X syndrome

Question 4

Lysosomal transport defect is seen in which of the following conditions?

Accepted Answer

Cystinosis

Answer

Gaucher's disease

Answer

Metachromatic leukodystrophy

Answer

Tay-Sachs disease

Question 5

Biochemical etiology of Alzheimer's disease relates to:

Accepted Answer

Acetylcholine

Answer

Dopamine

Answer

GABA

Answer

Serotonin

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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