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: 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: 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: Which is wrong about Crigler-Najjar syndrome Type-1?

It responds well to phenobarbital.. ***It responds well to phenobarbital.*** - **Crigler-Najjar syndrome Type 1** is characterized by a complete or near-complete absence of **UGT1A1 enzyme activity**, meaning there is no enzyme for phenobarbital to induce [1]. - Therefore, **phenobarbital** treatment, which works by inducing this enzyme, is ineffective in Type 1 [1]. *Kernicterus is usual.* - Due to the severe deficiency of **UGT1A1**, **unconjugated bilirubin** builds up to dangerously high levels, leading to **kernicterus** (bilirubin encephalopathy) in untreated infants [1]. - This neurological damage is a hallmark and often fatal complication of Crigler-Najjar Type 1 [1]. *Hepatic histology is normal.* - The primary defect in Crigler-Najjar Type 1 is a **functional enzyme deficiency**, not a structural one. - Thus, the liver cells themselves appear normal under microscopy, as there is no overt damage or inflammation. *Very high level of unconjugated bilirubin occurs in neonatal period.* - The complete or nearly complete absence of **UGT1A1** results in a severe inability to conjugate bilirubin, leading to extremely high levels of **unconjugated bilirubin** from birth [1]. - This presents as severe **neonatal jaundice**, which is persistent and life-threatening [1].

Q: Which of the following is a sex-linked disorder?

Hemophilia. ***Hemophilia*** - Hemophilia is an **X-linked recessive disorder**, meaning the gene responsible is located on the X chromosome. - Males are predominantly affected because they have only one X chromosome, so a single copy of the mutated gene is sufficient to cause the disease. *Neurofibromatosis* - Neurofibromatosis is an **autosomal dominant disorder**, meaning a single copy of the mutated gene on a non-sex chromosome is enough to cause the condition. - It affects males and females equally and is characterized by tumors along nerves and skin changes. *Klinefelter's syndrome* - Klinefelter's syndrome is a **chromosomal disorder** resulting from an extra X chromosome in males (XXY), not a single gene mutation on a sex chromosome. - While it involves sex chromosomes, it's categorized as a **sex chromosome aneuploidy** rather than a sex-linked disorder in the traditional genetic sense. *Thalassemia* - Thalassemia is an **autosomal recessive disorder**, meaning it requires two copies of the mutated gene (one from each parent) on non-sex chromosomes to manifest. - It affects the production of hemoglobin and impacts males and females equally.

Q: Chloride receptor defect is responsible for:

Cystic fibrosis. Cystic fibrosis - Cystic fibrosis (CF) is caused by mutations in the **CFTR gene**, which encodes the **cystic fibrosis transmembrane conductance regulator protein**, a **chloride channel** [1]. - A defective CFTR protein leads to abnormal chloride transport across epithelial cells, resulting in thick, viscous secretions in various organs like the lungs, pancreas, and sweat glands [1]. *Alpha-1 antitrypsin deficiency* - This condition is due to a genetic defect in the production of **alpha-1 antitrypsin**, a protective enzyme. - It primarily affects the lungs (emphysema) and liver (cirrhosis) and is not related to chloride receptor function. *Wilson's disease* - Wilson's disease is an autosomal recessive disorder characterized by accumulation of **copper** in various tissues, especially the liver, brain, and eyes. - It is caused by mutations in the **ATP7B gene**, which codes for a copper-transporting ATPase, not a chloride channel. *Hemochromatosis* - Hemochromatosis is a disorder of **iron overload** in the body, primarily due to excessive absorption of dietary iron. - It is often caused by mutations in the **HFE gene** and does not involve chloride receptor defects.

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

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 3

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 4

Intellectual disability is seen in?

Accepted Answer

Phenylketonuria

Answer

Von Gierke disease

Answer

Alkaptonuria

Answer

Albinism

Question 5

Which of the following has a polygenic pattern of inheritance?

Accepted Answer

Diabetes mellitus

Answer

Familial hypercholesterolemia

Answer

Resistant rickets

Answer

G6PD

Question 6

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 7

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 8

Which is wrong about Crigler-Najjar syndrome Type-1?

Accepted Answer

It responds well to phenobarbital.

Answer

Kernicterus is usual.

Answer

Hepatic histology is normal.

Answer

Very high level of unconjugated bilirubin occurs in neonatal period.

Question 9

Which of the following is a sex-linked disorder?

Accepted Answer

Hemophilia

Answer

Neurofibromatosis

Answer

Klinefelter's syndrome

Answer

Thalassemia

Question 10

Chloride receptor defect is responsible for:

Accepted Answer

Cystic fibrosis

Answer

Alpha-1 antitrypsin deficiency

Answer

Wilson's disease

Answer

Hemochromatosis

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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