Genetic Disorders and Biochemical Pathology Practice Questions

Q: The patient shown here is suffering from deficiency of which enzyme?

HGPRTase. ***HGPRTase*** - **HGPRTase deficiency** causes **Lesch-Nyhan syndrome** with characteristic **self-mutilation behavior**, choreoathetosis, and severe intellectual disability. - Clinical features include **orange sand-like crystals** in diapers due to hyperuricemia, **compulsive self-biting**, and **dystonia** as shown in the patient. *Adenosine deaminase* - **ADA deficiency** causes **SCID** with recurrent infections, lymphopenia, and failure to thrive in early infancy. - Clinical presentation focuses on **immunodeficiency** with chronic infections rather than neurological and behavioral abnormalities. *Xanthine oxidase* - **Xanthine oxidase deficiency** leads to **xanthinuria** with accumulation of xanthine causing kidney stones. - Patients present with **nephrolithiasis** and muscle pain but lack the neurological and self-destructive behaviors seen here. *Glucose-6-phosphate dehydrogenase* - **G6PD deficiency** causes **hemolytic anemia** triggered by oxidative stress from drugs, infections, or fava beans. - Features include **jaundice**, dark urine, and acute hemolysis but not the characteristic **neurological dysfunction** and **self-mutilation** of Lesch-Nyhan syndrome.

Q: The patient shown below has curly easily breakable hair. Which is correct about the condition?

Copper deficiency. ***Copper deficiency*** - **Copper deficiency** is characterized by **Menkes disease**, a genetic disorder leading to impaired copper absorption, resulting in characteristic **kinky, brittle hair** (pili torti), neurological degeneration, and connective tissue abnormalities. - Copper is a vital cofactor for **lysyl oxidase**, an enzyme critical for cross-linking collagen and elastin, and for **tyrosinase**, which is involved in melanin production. Its deficiency can lead to hair shaft abnormalities and hypopigmentation. *Selenium deficiency* - **Selenium deficiency** can lead to **Keshan disease**, a cardiomyopathy, and **Kashin-Beck disease**, an osteoarthropathy, but is not typically associated with curly, brittle hair. - While selenium is important for antioxidant defense and thyroid function, specific hair abnormalities beyond general thinning are not primary features of its deficiency. *Chromium deficiency* - **Chromium deficiency** is rare and primarily associated with impaired **glucose tolerance**, peripheral neuropathy, and weight loss. - There is no established link between chromium deficiency and the characteristic hair abnormalities described here. *Cobalt deficiency* - **Cobalt** is a component of **vitamin B12 (cobalamin)**, and its deficiency would manifest as symptoms of vitamin B12 deficiency, such as megaloblastic anemia and neurological dysfunction. - Isolated cobalt deficiency is extremely rare in humans, and it does not specifically cause curly, easily breakable hair.

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 that is afflicted. What is the inheritance pattern of this disorder? (Recent NEET Pattern 2016-17)

X-linked recessive. ***X-linked recessive*** - Hemophilia is a classic example of an **X-linked recessive disorder**, meaning the gene responsible is located on the X chromosome and two copies of the allele are necessary to show the trait (in females). - The father having hemophilia means he passed his **affected X chromosome** to all his daughters, making them carriers. The mother is a carrier with an affected son (the nephew). *Autosomal dominant* - In autosomal dominant inheritance, affected individuals typically appear in **every generation**, and an affected parent has a 50% chance of passing the trait to each child. - This pattern is inconsistent with the presented pedigree, as the disorder skips generations (father to grandson) and primarily affects males. *Autosomal recessive* - Autosomal recessive disorders typically **skip generations**, with affected individuals usually having unaffected parents who are heterozygous carriers. - However, in this case, the distribution of affected individuals (father and nephew, both male) and the carrier status of the daughter are not typical for a purely autosomal recessive pattern. *X-linked dominant* - In X-linked dominant inheritance, affected fathers transmit the trait to **all their daughters but none of their sons**. - This is contradicted by the information that the father has hemophilia (an X-linked recessive trait) and that his daughters are not affected but rather carriers.

Q: Wilson's disease has which of the following inheritance?

Autosomal recessive. ***Autosomal recessive*** - Wilson's disease is caused by mutations in the **ATP7B gene**, which codes for a copper-transporting ATPase. - For an individual to develop the disease, they must inherit **two copies of the mutated gene**, one from each parent. *It is an acquired disease* - Wilson's disease is a **genetic disorder**, meaning it is inherited, not acquired through environmental factors or lifestyle [1]. - While symptoms may manifest later in life, the underlying cause is a **predisposing genetic mutation** [1]. *X-linked recessive* - X-linked recessive disorders primarily affect males as they have only one X chromosome; however, Wilson's disease **affects both sexes equally**. - The gene responsible for Wilson's disease, **ATP7B**, is located on **chromosome 13**, an autosome, not on the X chromosome. *Autosomal dominant* - In autosomal dominant inheritance, only **one copy of the mutated gene** is sufficient to cause the disease, and it is usually seen in every generation. - Wilson's disease requires **two mutated copies** of the gene to manifest, and carriers (heterozygotes) are typically asymptomatic.

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

Vitamin D resistant rickets. ***Vitamin D resistant rickets*** - This condition is characterized by **impaired kidney reabsorption of phosphate** and **defective bone mineralization**, leading to rickets, and it is inherited in an **X-linked dominant pattern**. - In X-linked dominant traits, an affected father will pass the trait to **all his daughters**, but none of his sons. An affected mother has a 50% chance of passing the trait to **each child**, regardless of sex. *Colour blindness* - **Color blindness** is an **X-linked recessive** disorder, meaning it is more common in males. - Affected individuals have **difficulty distinguishing certain colors**, usually red and green. *Haemophilia-A* - **Hemophilia A** is an **X-linked recessive** disorder caused by a deficiency in **Factor VIII**, leading to uncontrolled bleeding. - Males are predominantly affected, while females are typically carriers. *Duchenne muscular dystrophy* - **Duchenne muscular dystrophy** is an **X-linked recessive** disorder characterized by progressive muscle degeneration and weakness due to a mutation in the **dystrophin gene**. - It primarily affects males, with symptoms often appearing in early childhood.

Q: Biochemical screening of newborn infants by heel-prick blood samples is performed by using the

Guthrie Card. ***Guthrie Card*** - The **Guthrie card**, also known as a **newborn screening card** or **filter paper card**, is specifically designed for collecting **heel-prick blood samples** from newborn infants for biochemical screening. - It allows for the detection of various **inborn errors of metabolism** and other genetic conditions, such as **phenylketonuria (PKU)** and **congenital hypothyroidism**. *Duchenne Card* - There is no specialized "Duchenne Card" used for **newborn biochemical screening**. - **Duchenne muscular dystrophy** is a genetic disorder diagnosed through **genetic testing** or **muscle biopsy**, not typically a specific screening card at birth. *Tay-Sachs Card* - There is no specific "Tay-Sachs Card" used for routine **newborn biochemical screening**. - **Tay-Sachs disease** is a **lysosomal storage disorder** diagnosed through enzyme activity tests or **genetic analysis**, often in populations at higher risk or with clinical suspicion. *Maple Card* - There is no recognized "Maple Card" for **newborn biochemical screening**. - "Maple" could potentially refer to **Maple Syrup Urine Disease (MSUD)**, which is one of the conditions screened for using the **Guthrie card**, but there is no dedicated "Maple Card."

Q: Which one of the following conditions is NOT inborn error of metabolism?

Neural tube defects. ***Neural tube defects*** - Neural tube defects are **birth defects** that occur when the **neural tube** fails to close completely during early fetal development, typically affecting the brain, spinal cord, or both. - While they are congenital, they are not classified as **inborn errors of metabolism** because they primarily result from structural developmental anomalies rather than enzymatic pathway dysfunctions. *Phenylketonuria (PKU)* - PKU is an **autosomal recessive** inborn error of metabolism caused by a deficiency of the enzyme **phenylalanine hydroxylase**, leading to a buildup of phenylalanine. - This enzymatic defect impairs the body's ability to metabolize **phenylalanine**, making it a classic example of an inborn error of metabolism. *Maple syrup urine disease* - This is an **autosomal recessive** inborn error of metabolism characterized by a defect in the metabolism of **branched-chain amino acids** (leucine, isoleucine, and valine) due to a deficiency in the enzyme branched-chain alpha-keto acid dehydrogenase. - The accumulation of these amino acids and their keto-acids gives the urine a characteristic **maple syrup odor**. *Tay-Sachs disease* - Tay-Sachs disease is a fatal, **autosomal recessive** inborn error of metabolism caused by a deficiency of the enzyme **hexosaminidase A**. - This enzyme deficiency leads to the harmful accumulation of fatty acid derivatives called **gangliosides** in nerve cells in the brain, resulting in progressive neurological degeneration.

Q: Which membrane channel is mainly affected in Cystic fibrosis?

Chloride. ***Chloride*** - Cystic fibrosis is caused by a mutation in the **CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)** gene, which encodes a chloride channel. - Dysfunction of this **chloride channel** leads to impaired transport of chloride ions, mainly affecting epithelial cells in various organs. *Sodium* - While sodium transport is indirectly affected in cystic fibrosis, the primary defect is not in a sodium channel itself but rather in the **chloride channel**, which influences water and sodium movement. - The abnormal **chloride transport** leads to a compensatory but ineffective increase in sodium absorption in some tissues like the airway. *Calcium* - Calcium channels are not primarily implicated in the pathophysiology of **cystic fibrosis**. - **Calcium dysregulation** can occur secondarily in some CF-related processes, but it is not the main affected membrane channel. *Potassium* - **Potassium channels** are not the main membrane channels affected in cystic fibrosis. - While potassium transport is vital for cellular function, it is not the primary defect underlying the disease's respiratory and gastrointestinal manifestations.

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.

Question 1

The patient shown here is suffering from deficiency of which enzyme?

Accepted Answer

HGPRTase

Answer

Xanthine oxidase

Answer

Glucose-6-phosphate dehydrogenase

Answer

Adenosine deaminase

Question 2

The patient shown below has curly easily breakable hair. Which is correct about the condition?

Accepted Answer

Copper deficiency

Answer

Selenium deficiency

Answer

Chromium deficiency

Answer

Cobalt deficiency

Question 3

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 that is afflicted. What is the inheritance pattern of this disorder? (Recent NEET Pattern 2016-17)

Accepted Answer

X-linked recessive

Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Question 4

Wilson's disease has which of the following inheritance?

Accepted Answer

Autosomal recessive

Answer

It is an acquired disease

Answer

X-linked recessive

Answer

Autosomal dominant

Question 5

Which of the following is X-linked dominant trait?

Accepted Answer

Vitamin D resistant rickets

Answer

Colour blindness

Answer

Haemophilia-A

Answer

Duchenne muscular dystrophy

Question 6

Biochemical screening of newborn infants by heel-prick blood samples is performed by using the

Accepted Answer

Guthrie Card

Answer

Duchenne Card

Answer

Tay-Sachs Card

Answer

Maple Card

Question 7

Which one of the following conditions is NOT inborn error of metabolism?

Accepted Answer

Neural tube defects

Answer

Phenylketonuria (PKU)

Answer

Maple syrup urine disease

Answer

Tay-Sachs disease

Question 8

Which membrane channel is mainly affected in Cystic fibrosis?

Accepted Answer

Chloride

Answer

Sodium

Answer

Calcium

Answer

Potassium

Question 9

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

Accepted Answer

Point mutation

Answer

Deletion

Answer

Insertion

Answer

Translocation

Question 10

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

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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