Genetic Disorders and Biochemical Pathology Practice Questions

Q: What is the most common cause of pure gonadal dysgenesis with XY karyotype?

Point mutation. Point mutation - The most common genetic cause of **pure gonadal dysgenesis with XY karyotype** (Swyer syndrome) is a **point mutation** within the **SRY gene**, located on the Y chromosome [1]. - Point mutations include **missense mutations** (amino acid substitution) and **nonsense mutations** (premature stop codon), both of which can render the SRY protein non-functional. - This specific type of mutation leads to a non-functional SRY protein, preventing the development of testes in an individual with an XY karyotype and resulting in streak gonads [1]. *Deletion* - While deletions involving the SRY gene can cause XY gonadal dysgenesis, **complete deletion** of SRY is less common than point mutations as the primary cause of pure gonadal dysgenesis. - Larger deletions on the Y chromosome might also affect other genes, leading to a broader spectrum of phenotypes. *Insertion* - **Insertions** are a type of frameshift mutation where nucleotides are added to the DNA sequence. - While insertions in the SRY gene could theoretically cause gonadal dysgenesis, they are much less commonly reported than point mutations as the cause of Swyer syndrome. *Translocation* - **Translocations** involving the SRY gene, such as SRY being translocated to an X chromosome, can lead to sex reversal (XX male phenotype). - However, for pure XY gonadal dysgenesis (where SRY is present but non-functional), translocations are not the most common underlying genetic mechanism.

Q: Pompe disease is seen due to deficiency of?

Lysosomal acid alpha glucosidase. ***Lysosomal acid alpha glucosidase*** - **Pompe disease**, also known as **glycogen storage disease type II**, is caused by the deficiency of **acid alpha-glucosidase (GAA)**, a lysosomal enzyme. - This deficiency leads to the accumulation of **glycogen** within lysosomes in various tissues, particularly muscle, liver, and heart, causing muscle weakness and cardiomegaly. *β-galactocerebrosidase* - Deficiency of **β-galactocerebrosidase** is associated with **Krabbe disease** (globoid cell leukodystrophy). - Krabbe disease involves the buildup of **galactocerebroside**, leading to progressive destruction of the myelin sheath in the central and peripheral nervous systems. *β-glucocerebrosidase* - Deficiency in **β-glucocerebrosidase** causes **Gaucher disease**, the most common lysosomal storage disorder. - This results in the accumulation of **glucocerebroside** in macrophages, leading to hepatosplenomegaly, bone pain, and neurologic symptoms in some forms. *β-hexosaminidase-A* - Deficiency of **β-hexosaminidase-A** is the underlying cause of **Tay-Sachs disease**. - Tay-Sachs disease is characterized by the accumulation of **GM2 gangliosides** in neurons, leading to progressive neurodegeneration, developmental delay, and a characteristic cherry-red spot in the retina.

Q: A 28-year-old woman comes to the physician for genetic counseling prior to conception. For the past year, she has had intermittent episodes of headache, nausea, abdominal pain, and tingling of her fingers. She also complains of dark urine during the episodes. Her mother and maternal uncle have similar symptoms and her father is healthy. Her husband is healthy and there is no history of serious illness in his family. Serum studies show elevated concentrations of porphobilinogen and δ-aminolevulinic acid. What is the probability of this patient having a child with the same disease as her?

50%. ***50%*** - This patient's symptoms (headache, nausea, abdominal pain, tingling, dark urine) and elevated **porphobilinogen** and **δ-aminolevulinic acid** are highly suggestive of **Acute Intermittent Porphyria** (AIP). - AIP is an **autosomal dominant** disorder. Therefore, there is a **50% chance** that any child of an affected parent will inherit the disease-causing allele. - Since her husband is healthy with no family history, he does not carry the mutation, making this a straightforward autosomal dominant inheritance calculation. *25%* - This probability would be expected in an **autosomal recessive** inheritance pattern when two carrier parents have a child, which is not the case here. - It would also be the probability for an X-linked recessive disorder if the mother is a carrier and the father is unaffected, and they are discussing a son's inheritance. - The clinical presentation and family history (mother and maternal uncle affected, consistent with autosomal dominant pattern) rule out this probability. *67%* - This probability is seen in specific genetic scenarios, such as the chance of a phenotypically normal sibling of an individual with an autosomal recessive disease being a carrier. - It's not a standard probability for direct offspring of an affected individual with an autosomal dominant condition. - This does not apply to the straightforward inheritance question being asked here. *100%* - This probability would occur if the disease were inherited in an **autosomal dominant** manner and the affected parent was **homozygous dominant** for the mutation. - However, this is extremely rare in AIP, as most affected individuals are **heterozygous**. - The family history pattern (affected mother with unaffected father having an affected child) is consistent with heterozygosity, not homozygosity.

Q: Intellectual disability is seen in?

Phenylketonuria. ***Phenylketonuria*** - **Phenylketonuria (PKU)** is an inherited metabolic disorder where the body cannot process the amino acid **phenylalanine**, leading to its accumulation in the blood and brain. - Untreated PKU results in severe neurological problems, including **intellectual disability**, seizures, and developmental delays. *Von Gierke disease* - **Von Gierke disease** is a type of glycogen storage disease primarily affecting the liver and kidneys, causing **hypoglycemia** and **lactic acidosis**. - It does not typically involve intellectual disability; cognitive development is usually normal if metabolic complications are managed. *Alkaptonuria* - **Alkaptonuria** is an inherited disorder characterized by the accumulation of **homogentisic acid**, leading to dark urine, ochronosis (bluish-black discoloration of cartilage and connective tissue), and arthritis. - It does not cause intellectual disability. *Albinism* - **Albinism** is a group of inherited disorders characterized by a reduced or complete lack of **melanin pigment** in the skin, hair, and eyes. - While it causes vision problems, such as photosensitivity and nystagmus, it is not associated with intellectual disability.

Q: Which of the following has a polygenic pattern of inheritance?

Diabetes mellitus. **Diabetes mellitus** - **Type 2 Diabetes Mellitus**, the most common form, is a classic example of a **polygenic disease**, meaning it results from the interaction of multiple genes and environmental factors. - Many genes contribute to aspects like **insulin resistance** and **beta-cell dysfunction**, leading to the disease. *Familial hypercholesterolemia* - This condition is inherited in an **autosomal dominant** pattern, primarily due to mutations in a single gene, most commonly the **LDL receptor gene**. - While other genes can influence cholesterol levels, the severe form of familial hypercholesterolemia is typically **monogenic**. *Resistant rickets* - **X-linked hypophosphatemia**, also known as vitamin D-resistant rickets, is inherited in an **X-linked dominant** pattern. - It is caused by mutations in the **PHEX gene**, which affects phosphate reabsorption in the kidneys. *G6PD* - **Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)** is an **X-linked recessive** disorder. - It is caused by mutations in a single gene on the X chromosome, making it a **monogenic** condition.

Q: Which of the following is an X-linked dominant disorder?

Vitamin D resistant rickets. ***Vitamin D resistant rickets*** - This is an **X-linked dominant** disorder characterized by impaired renal phosphate reabsorption and defective vitamin D metabolism, leading to **rickets-like symptoms** despite adequate vitamin D intake. - Affected individuals show **hypophosphatemia** and bone defects, with sons and daughters of affected fathers being affected. *Red-green color blindness* - This is an **X-linked recessive** disorder, meaning it primarily affects males and is passed from carrier mothers to their sons. - Affected individuals have difficulty distinguishing **red and green hues** due to defects in cone photoreceptors. *Achondroplasia* - This is an **autosomal dominant** disorder caused by a mutation in the **FGFR3 gene**, leading to dwarfism. - It is not X-linked and affects both sexes equally, with an affected individual having a 50% chance of passing it to each child. *Familial hypercholesterolemia* - This is an **autosomal dominant** metabolic disorder characterized by extremely high levels of **LDL cholesterol** due to defects in the LDL receptor. - It is not X-linked and can lead to premature cardiovascular disease, affecting both males and females.

Q: Acid maltase deficiency occurs in

Pompe's disease. ***Pompe's disease*** - **Pompe's disease**, also known as Glycogen Storage Disease Type II, is caused by a deficiency of the lysosomal enzyme **alpha-1,4-glucosidase**, also called **acid maltase**. - This deficiency leads to the accumulation of **glycogen** in lysosomes within various tissues, particularly muscle, liver, and heart, causing muscle weakness and cardiomyopathy. *Von Gierke's disease* - **Von Gierke's disease** (Glycogen Storage Disease Type Ia) is caused by a deficiency of **glucose-6-phosphatase**, leading to accumulation of glycogen primarily in the liver and kidneys. - It presents with severe **hypoglycemia** and hepatomegaly, rather than acid maltase deficiency. *McArdle's disease* - **McArdle's disease** (Glycogen Storage Disease Type V) results from a deficiency of **muscle glycogen phosphorylase**. - This deficiency causes exercise intolerance, muscle pain, and cramps, and is not related to acid maltase. *Niemann-Pick disease* - **Niemann-Pick disease** is a group of lysosomal storage disorders caused by deficiencies in enzymes like **sphingomyelinase** (Type A and B) or mutations in the NPC1/NPC2 genes (Type C). - It leads to accumulation of **sphingomyelin** and cholesterol, affecting the liver, spleen, lungs, and brain, and is unrelated to glycogen metabolism or acid maltase.

Q: Pattern of inheritance where mother transmits disease to all children -

Mitochondrial inheritance. ***Mitochondrial inheritance*** - Mitochondrial DNA (mtDNA) is exclusively inherited from the **mother**, meaning all children of an affected mother will inherit the mitochondrial disease. - Fathers do not pass on their mtDNA to their offspring, so an affected father's children will not inherit mitochondrial conditions from him. *X-linked recessive* - In X-linked recessive inheritance, sons have a 50% chance of being affected if their mother is a carrier, and daughters have a 50% chance of being carriers. - It does not guarantee that **all children** will inherit the disease from an affected mother; affected mothers would pass the X-linked gene to all sons (who would be affected) and all daughters (who would be carriers or affected depending on the other X chromosome). *Autosomal dominant* - In autosomal dominant inheritance, an affected parent has a 50% chance of passing the allele to **each child**, regardless of sex. - This pattern means not all children will necessarily inherit the disease, and both sexes are affected equally. *Autosomal recessive* - For autosomal recessive diseases, both parents must be carriers or affected for a child to inherit the disease, and even then, there is only a 25% chance for each child to be affected if both parents are carriers. - This pattern does not result in **all children** inheriting the disease from an affected mother, as it requires contributions from both parents.

Q: The most potent bone resorbing interleukin is

IL-1β. ***IL-1β*** - **Interleukin-1 beta (IL-1β)** is a powerful proinflammatory cytokine that plays a crucial role in bone resorption by stimulating osteoclast activity and formation. - It increases the expression of **RANKL (receptor activator of nuclear factor-κB ligand)** on stromal cells and osteoblasts, which then binds to RANK on osteoclast precursors, promoting their differentiation and activation. *IL-5* - **Interleukin-5 (IL-5)** is primarily involved in the growth and differentiation of **eosinophils** and B cells, playing a role in allergic reactions and parasitic infections. - It does not have a significant direct role in **bone resorption**. *IL-8* - **Interleukin-8 (IL-8)**, also known as **CXCL8**, is a chemokine that primarily acts as a chemoattractant for **neutrophils**, guiding them to sites of inflammation. - While inflammation can indirectly impact bone, IL-8 itself is **not a primary bone-resorbing cytokine**. *IL-3* - **Interleukin-3 (IL-3)** is a **hematopoietic growth factor** that promotes the proliferation and differentiation of various myeloid and lymphoid progenitor cells. - It is involved in **blood cell formation** rather than directly influencing **bone resorption**.

Question 1

What is the most common cause of pure gonadal dysgenesis with XY karyotype?

Accepted Answer

Point mutation

Answer

Deletion

Answer

Insertion

Answer

Translocation

Question 2

Pompe disease is seen due to deficiency of?

Accepted Answer

Lysosomal acid alpha glucosidase

Answer

β-galactocerebrosidase

Answer

β-glucocerebrosidase

Answer

β-hexosaminidase-A

Question 3

A 5-month-old boy is brought to his pediatrician because his parents have noticed that he has very restricted joint movement. He was born at home without prenatal care, but they say that he appeared healthy at birth. Since then, they say that he doesn't seem to move very much and is hard to arouse. Physical exam reveals coarse facial structures and hepatosplenomegaly. Radiography reveals skeletal malformations, and serum tests show high plasma levels of lysosomal enzymes. The production of which of the following substances will most likely be disrupted in this patient?

Accepted Answer

Mannose-6-phosphate

Answer

Glucocerebroside

Answer

Heparan sulfate

Answer

Ceramide

Question 4

A 28-year-old woman comes to the physician for genetic counseling prior to conception. For the past year, she has had intermittent episodes of headache, nausea, abdominal pain, and tingling of her fingers. She also complains of dark urine during the episodes. Her mother and maternal uncle have similar symptoms and her father is healthy. Her husband is healthy and there is no history of serious illness in his family. Serum studies show elevated concentrations of porphobilinogen and δ-aminolevulinic acid. What is the probability of this patient having a child with the same disease as her?

Accepted Answer

50%

Answer

25%

Answer

67%

Answer

100%

Question 5

Intellectual disability is seen in?

Accepted Answer

Phenylketonuria

Answer

Von Gierke disease

Answer

Alkaptonuria

Answer

Albinism

Question 6

Which of the following has a polygenic pattern of inheritance?

Accepted Answer

Diabetes mellitus

Answer

Familial hypercholesterolemia

Answer

Resistant rickets

Answer

G6PD

Question 7

Which of the following is an X-linked dominant disorder?

Accepted Answer

Vitamin D resistant rickets

Answer

Red green color blindness

Answer

Achondroplasia

Answer

Familial hypercholesterolemia

Question 8

Acid maltase deficiency occurs in

Accepted Answer

Pompe's disease

Answer

Von Gierke's disease

Answer

McArdle's disease

Answer

Niemann-Pick disease

Question 9

Pattern of inheritance where mother transmits disease to all children -

Accepted Answer

Mitochondrial inheritance

Answer

X-linked recessive

Answer

Autosomal dominant

Answer

Autosomal recessive

Question 10

The most potent bone resorbing interleukin is

Accepted Answer

IL-1β

Answer

IL - 5

Answer

IL - 8

Answer

IL - 3

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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