Genetic Disorders and Biochemical Pathology Practice Questions

Q: During evaluation of a child with intellectual disability following findings were noted. These point to deficiency of?

Alpha-L-Iduronidase. ***Alpha-L-Iduronidase*** - The image shows **coarse facial features**, **corneal clouding**, and an **umbilical hernia**, which are characteristic signs of Hurler syndrome (MPS I). - Hurler syndrome is caused by a deficiency of the enzyme **alpha-L-iduronidase**, leading to the accumulation of dermatan sulfate and heparan sulfate. *L-sulfoiduronate sulfatase* - Deficiency of **L-sulfoiduronate sulfatase** causes Hunter syndrome (MPS II). - Hunter syndrome spares the **cornea** (no corneal clouding) and has a different clinical presentation, including X-linked inheritance. *Heparan sulfate sulfamidase* - A deficiency in **heparan sulfate sulfamidase** leads to Sanfilippo syndrome (MPS IIIA). - While Sanfilippo syndrome involves severe neurodegeneration, it typically lacks the prominent **skeletal abnormalities** and **corneal clouding** seen in Hurler syndrome. *N-acetylgalactosamine-4-sulfatase* - Deficiency of **N-acetylgalactosamine-4-sulfatase** causes Maroteaux-Lamy syndrome (MPS VI). - Maroteaux-Lamy syndrome is characterized by severe skeletal involvement and corneal clouding but generally has preservation of **intellectual function**, unlike Hurler syndrome.

Q: A 10-month-old child with coarse facies is referred for developmental delay. On examination, hepatosplenomegaly was noted. WBC N-acetylglucosamine-1-phosphotransferase activity was absent. The X-ray is shown below. What is the diagnosis?

I cell disease. ***I cell disease*** - **I-cell disease** (Mucolipidosis II) is characterized by **coarse facial features**, developmental delay, hepatosplenomegaly, and **skeletal abnormalities** (dysostosis multiplex) seen on X-ray, which are consistent with the image. - The absence of **N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase)** activity leads to misrouting of lysosomal enzymes, resulting in accumulation of mucolipids within cells. *MPS type II* - **MPS type II** (Hunter syndrome) also presents with coarse facies, developmental delay, and hepatosplenomegaly, and can show skeletal abnormalities. - However, the enzymatic defect is in **iduronate sulfatase**, not GlcNAc-1-phosphotransferase, and the clinical course tends to be slightly milder than I-cell disease, particularly in early infancy. *Proteus syndrome* - **Proteus syndrome** is characterized by **overgrowth of tissues**, asymmetric growth, and various tumors, not by the specific metabolic defect or typical pattern of skeletal changes described. - It does not involve absent GlcNAc-1-phosphotransferase activity. *Larsen syndrome* - **Larsen syndrome** primarily involves **skeletal abnormalities**, such as joint dislocations (especially knees, hips, and elbows), flattened facial appearance, and clubfoot. - It does not feature the same metabolic defect (absent GlcNAc-1-phosphotransferase activity) or the prominent coarse facial features and hepatosplenomegaly seen in the patient.

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.

Question 1

During evaluation of a child with intellectual disability following findings were noted. These point to deficiency of?

Accepted Answer

Alpha-L-Iduronidase

Answer

L-sulfoiduronate sulfatase

Answer

Heparan sulfate sulfamidase

Answer

N-acetylgalactosamine-4-sulfatase

Question 2

A 10-month-old child with coarse facies is referred for developmental delay. On examination, hepatosplenomegaly was noted. WBC N-acetylglucosamine-1-phosphotransferase activity was absent. The X-ray is shown below. What is the diagnosis?

Accepted Answer

I cell disease

Answer

MPS type II

Answer

Proteus syndrome

Answer

Larsen syndrome

Question 3

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 4

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 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 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 6

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 7

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 8

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 9

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 10

Which membrane channel is mainly affected in Cystic fibrosis?

Accepted Answer

Chloride

Answer

Sodium

Answer

Calcium

Answer

Potassium

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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