Genetic Disorders and Biochemical Pathology Practice Questions

Q: Gaucher's disease is:

Autosomal recessive inheritance. ***Autosomal recessive inheritance*** - **Gaucher's disease** is caused by a deficiency of the enzyme **glucocerebrosidase**, leading to the accumulation of glucocerebroside in macrophages. - This genetic disorder requires two copies of the defective gene (one from each parent) to manifest, which is characteristic of **autosomal recessive inheritance**. *Autosomal dominant inheritance* - In **autosomal dominant inheritance**, only one copy of the defective gene is needed for the disease to occur, which is not the case for Gaucher's disease. - Affected individuals usually have at least one affected parent, and there is a 50% chance of passing the condition to offspring. *X-linked recessive inheritance* - **X-linked recessive inheritance** primarily affects males, as the gene is located on the X chromosome. - Females are typically carriers and are less commonly affected, which does not describe the inheritance pattern of Gaucher's disease. *X-linked dominant inheritance* - **X-linked dominant inheritance** means the disease can affect both males and females, but females are typically more mildly affected. - All daughters of an affected father will inherit the condition, which is not consistent with Gaucher's disease.

Q: Which one of the following diseases is classified as an autosomal dominant disorder?

Maturity onset diabetes of the young. ***Maturity onset diabetes of the young*** - **Maturity onset diabetes of the young (MODY)** is a genetically heterogeneous group of single-gene disorders characterized by beta-cell dysfunction and impaired insulin secretion, typically inherited in an **autosomal dominant pattern** [1]. - A single copy of the mutated gene is sufficient to cause the condition, leading to diabetes usually before the age of 25, often without obesity or autoantibodies [1]. *Hemochromatosis* - **Hemochromatosis** is typically inherited in an **autosomal recessive pattern**, meaning two copies of the mutated gene (e.g., *HFE* gene) are required for the disease to manifest. - It leads to excessive iron absorption and tissue iron overload. *Phenylketonuria* - **Phenylketonuria (PKU)** is an **autosomal recessive disorder** caused by a deficiency in the enzyme **phenylalanine hydroxylase**, necessitating two mutated gene copies for the disease to occur. - This leads to the accumulation of phenylalanine, causing neurological damage if untreated. *Glucose-6 phosphate dehydrogenase deficiency* - **Glucose-6 phosphate dehydrogenase (G6PD) deficiency** is an **X-linked recessive disorder**, meaning the gene is located on the X chromosome and typically affects males more severely. - Females can be carriers, and hemizygous males (having only one X chromosome) will express the disorder if they inherit the mutated gene.

Q: Which of the following porphyrias is not inherited as an autosomal dominant disorder?

Congenital Erythropoietic Porphyria. ***Congenital Erythropoietic Porphyria*** - This porphyria is inherited in an **autosomal recessive** pattern, meaning two copies of the defective gene (one from each parent) are required for the disease to manifest. - It results from a deficiency in **uroporphyrinogen III synthase (URO-synthase)**, leading to the accumulation of uroporphyrinogen I and coproporphyrinogen I isomers. *Acute Intermittent Porphyria* - This is an **autosomal dominant** disorder caused by a deficiency in **hydroxymethylbilane synthase (HMBS)**, also known as porphyrobilinogen deaminase (PBG deaminase). - It primarily affects the nervous system, leading to acute neurovisceral attacks. *Porphyria Cutanea Tarda* - This is **primarily sporadic (acquired)** in about 80% of cases, often associated with hepatic iron overload, alcohol use, hepatitis C, or estrogen use. - Only about 20% of cases are familial with **autosomal dominant** inheritance pattern. - It is caused by a deficiency in **uroporphyrinogen decarboxylase (UROD)**, leading to photosensitivity due to accumulated porphyrins in the skin. *Hereditary Coproporphyria* - This is an **autosomal dominant** disorder caused by a deficiency in **coproporphyrinogen oxidase (CPOX)**. - It can present with both neurovisceral attacks and photosensitivity, depending on the accumulated porphyrins.

Q: The PRSS1 gene is located on?

Chr 7q. ***Chr 7q*** - The **PRSS1 gene**, which encodes for **cationic trypsinogen**, is located on the long arm (**q arm**) of **chromosome 7**. - Mutations in this gene are strongly associated with **hereditary pancreatitis**. *Chr 20q* - This chromosome location is associated with various other genes and diseases, but not typically with the **PRSS1 gene** or **hereditary pancreatitis**. - For example, genes related to **diabetes** and **obesity** are found on chromosome 20. *Chr 17p* - This region is known for containing several important genes, such as **TP53** (a tumor suppressor gene), but it is not the location for **PRSS1**. - Deletions or mutations in **17p** are linked to conditions like **Li-Fraumeni syndrome**. *Chr 1p* - **Chromosome 1**, specifically the short arm (**p arm**), contains a large number of genes and is implicated in many diseases, including certain **cancers**. - However, the **PRSS1 gene** is not found at this chromosomal location.

Q: A 34-year-old, G1P0, presents for genetic counseling at 12 weeks' gestation. The patient has two sisters and a brother; her father has hemophilia. Her siblings are not affected, but she has a nephew who is affected. What is the inheritance pattern of this disorder?

X-linked inheritance. ***X-linked inheritance*** - Hemophilia is an **X-linked recessive disorder** - An affected father passes his X chromosome mutation to **all daughters**, making them **obligate carriers** (not affected but carry the gene) - The affected nephew (son of patient's sister) confirms the patient's sister is a carrier who passed the affected X chromosome to her son - Classic pattern: affected males, carrier females, skips generations through female carriers *Autosomal recessive* - Would require both parents to be carriers for offspring to be affected - An affected father would pass one mutant allele to all children, but this wouldn't make daughters obligate carriers unless mother also carried the gene - Pattern of father → carrier daughter → affected grandson is not typical of autosomal recessive inheritance *Mitochondrial inheritance* - Only transmitted from mother to **all children** regardless of gender - Affected father **cannot** pass mitochondrial disorders to offspring - Would show maternal transmission pattern with all children of affected mothers being affected *Multifactorial inheritance* - Involves combination of multiple genes and environmental factors - Does not follow clear Mendelian pattern - The distinct single-gene pattern (affected father, carrier daughters, affected male grandchild) indicates X-linked recessive, not multifactorial

Q: Which of the following is a genetic disorder that does not primarily affect ion channels?

Tay-Sachs disease. ***Cystic fibrosis*** - Primarily caused by mutations in the **CFTR gene**, which encodes a **chloride channel**, but it is not classified as a classic channelopathy. - The disease mainly affects **mucus production** rather than direct dysfunction of ion channels in the traditional sense. [1] *Hypokalemic periodic paralysis* - This condition is directly related to **ion channel dysfunction**, specifically affecting **sodium channels** in muscle cells. - It causes episodic **muscle weakness** and hypokalemia due to improper ion transport. *Liddle's syndrome* - A genetic disorder resulting from mutations affecting **epithelial sodium channels**, leading to **hypertension**. - It exemplifies classic channelopathy by causing dysregulation of sodium reabsorption in the kidneys. *Tay-sach's disease* - A ***gangliosidosis*** caused by a deficiency in the enzyme **Hexosaminidase A**, rather than ion channel dysfunction. - It results in the accumulation of **GM2 gangliosides** leading to neurological degeneration, not affecting ion channels directly. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 120-122.

Q: In which of the following inheritance patterns is father-to-son transmission not observed?

X-linked recessive inheritance. ***X-linked recessive inheritance*** - In X-linked inheritance, females have two X chromosomes (XX) and males have one X and one Y chromosome (XY). A father always passes his **Y chromosome** to his son. - He passes his **X chromosome only to his daughters**. Therefore, a father cannot pass an X-linked trait directly to his son. *Autosomal dominant inheritance* - In autosomal dominant inheritance, a disease allele is located on a **non-sex chromosome (autosome)**. - Both males and females can be affected, and **father-to-son transmission is possible** if the father carries the dominant allele on an autosome. *Autosomal recessive inheritance* - This inheritance pattern also involves genes on **autosomes**. - A father can transmit a recessive allele to his son, though the son would only express the trait if he also inherits a recessive allele from his mother. **Father-to-son transmission of the allele is possible**. *Multifactorial inheritance* - This pattern involves the interaction of **multiple genes** and **environmental factors**. - As some of these genes are on autosomes, and environmental factors are independent of sex chromosomes, **father-to-son transmission is observed** for the genetic components.

Q: What is the type of inheritance in MELAS?

Mitochondrial. ***Mitochondrial*** - **MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes)** is caused by mutations in **mitochondrial DNA**. - **Mitochondrial inheritance** shows **maternal transmission** - the disease is passed from mothers to all of their children (both sons and daughters), but **only daughters can transmit it to the next generation** as sons do not pass on mitochondrial DNA. - This occurs because mitochondria are inherited exclusively from the egg (maternal), not from sperm. *X-linked Recessive* - **X-linked recessive disorders** primarily affect males, as they only have one X chromosome. - The disease is typically transmitted by carrier mothers to their sons, which is not characteristic of MELAS. *Autosomal Recessive* - In **autosomal recessive inheritance**, an individual must inherit two copies of the mutated gene (one from each parent) to be affected. - This pattern of inheritance does not explain the strict maternal transmission observed in MELAS. *X-linked Dominant* - **X-linked dominant disorders** can affect both males and females, but females are often more mildly affected. - All daughters of an affected father will inherit the condition, which differs from the maternal-only inheritance pattern of MELAS.

Q: In Marfan syndrome, the defect is in the gene encoding which protein?

Fibrillin I. ***Fibrillin I*** - Marfan syndrome arises from a defect in **fibrillin I**, which is essential for the proper formation of elastic fibers in connective tissue [1]. - This defect leads to symptoms affecting the **musculoskeletal**, **cardiovascular**, and **ocular systems** due to weakened connective tissue structure [1]. *Collagen* - While collagen is an important structural protein, it is not the primary defect in Marfan syndrome. - Disorders affecting collagen include **Ehlers-Danlos syndrome**, which presents with different clinical features such as hypermobility. *Fibrillin II* - Fibrillin II is related to different connective tissue conditions but is not involved in Marfan syndrome. - Its mutations are associated with **other disorders**, not the hallmark manifestations seen in Marfan. *Elastin* - Elastin provides elasticity in vascular and other tissues; however, it is not directly related to Marfan syndrome. - Conditions such as **Williams syndrome** involve elastin, but they present distinct clinical features from Marfan syndrome. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. With Illustrations By, pp. 35-36.

Q: Enzyme deficiencies are seen in genetic diseases such as?

Tay-Sachs disease. ***Tay-Sachs disease*** - Tay-Sachs disease is a **lysosomal storage disorder** caused by a deficiency of the enzyme **hexosaminidase A**. - This enzyme deficiency leads to the accumulation of **GM2 gangliosides** in neurons, resulting in progressive neurological degeneration. *Sickle Cell Anemia* - Sickle cell anemia is a **hemoglobinopathy** caused by a genetic mutation affecting the structure of the **beta-globin chain** of hemoglobin, leading to abnormal red blood cell shape. - It is not primarily due to an enzyme deficiency, but rather a structural protein defect. *Cystic Fibrosis* - Cystic fibrosis is caused by a mutation in the **CFTR gene**, which encodes a **chloride channel protein**. - This defect affects chloride transport across cell membranes, leading to thick, viscous secretions in various organs, not an enzyme deficiency. *Duchenne Muscular Dystrophy* - Duchenne muscular dystrophy is an **X-linked recessive disorder** characterized by a deficiency of the protein **dystrophin**. - Dystrophin is a structural protein essential for muscle cell integrity; its absence leads to progressive muscle degeneration, not an enzyme deficiency.

Question 1

Gaucher's disease is:

Accepted Answer

Autosomal recessive inheritance

Answer

Autosomal dominant inheritance

Answer

X-linked recessive inheritance

Answer

X-linked dominant inheritance

Question 2

Which one of the following diseases is classified as an autosomal dominant disorder?

Accepted Answer

Maturity onset diabetes of the young

Answer

Hemochromatosis

Answer

Phenylketonuria

Answer

Glucose-6 phosphate dehydrogenase deficiency

Question 3

Which of the following porphyrias is not inherited as an autosomal dominant disorder?

Accepted Answer

Congenital Erythropoietic Porphyria

Answer

Porphyria Cutanea Tarda

Answer

Hereditary Coproporphyria

Answer

Acute Intermittent Porphyria

Question 4

The PRSS1 gene is located on?

Accepted Answer

Chr 7q

Answer

Chr 20q

Answer

Chr 17p

Answer

Chr 1p

Question 5

A 34-year-old, G1P0, presents for genetic counseling at 12 weeks' gestation. The patient has two sisters and a brother; her father has hemophilia. Her siblings are not affected, but she has a nephew who is affected. What is the inheritance pattern of this disorder?

Accepted Answer

X-linked inheritance

Answer

Autosomal recessive

Answer

Mitochondrial inheritance

Answer

Multifactorial inheritance

Question 6

Which of the following is a genetic disorder that does not primarily affect ion channels?

Accepted Answer

Tay-Sachs disease

Answer

Cystic fibrosis

Answer

Liddle's syndrome

Answer

Hypokalemic periodic paralysis

Question 7

In which of the following inheritance patterns is father-to-son transmission not observed?

Accepted Answer

X-linked recessive inheritance

Answer

Autosomal dominant inheritance

Answer

Autosomal recessive inheritance

Answer

Multifactorial inheritance

Question 8

What is the type of inheritance in MELAS?

Accepted Answer

Mitochondrial

Answer

X-linked Recessive

Answer

Autosomal Recessive

Answer

X-linked Dominant

Question 9

In Marfan syndrome, the defect is in the gene encoding which protein?

Accepted Answer

Fibrillin I

Answer

Fibrillin II

Answer

Elastin

Answer

Collagen

Question 10

Enzyme deficiencies are seen in genetic diseases such as?

Accepted Answer

Tay-Sachs disease

Answer

Sickle Cell Anemia

Answer

Cystic Fibrosis

Answer

Duchenne Muscular Dystrophy

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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