Genetic and Metabolic Disorders Practice Questions

Q: Wilms' tumor associated with all except -

Digeorge syndrome. ***Digeorge syndrome*** - **DiGeorge syndrome** is a genetic disorder associated with T-cell immunodeficiency, hypocalcemia, and **congenital heart defects**, but *not* primarily with Wilms' tumor. - It results from a deletion on **chromosome 22q11.2**, leading to abnormal development of the third and fourth pharyngeal pouches. *Beckwith-Wiedemann syndrome* - **Beckwith-Wiedemann syndrome** is closely associated with an increased risk of **Wilms' tumor**, often presenting with macrosomia, macroglossia, and omphalocele. - It is linked to abnormalities on **chromosome 11p15.5**, affecting growth regulation. *Denys-Drash syndrome* - **Denys-Drash syndrome** is characterized by the triad of **Wilms' tumor**, **diffuse mesangial sclerosis** (leading to renal failure), and male **pseudohermaphroditism**. - It is caused by mutations in the **WT1 gene**. *WAGR syndrome* - **WAGR syndrome** is an acronym for **W**ilms' tumor, **A**niridia, **G**enitourinary anomalies, and **R**ange of developmental delays. - This syndrome is caused by a deletion on **chromosome 11p13**, encompassing both the **PAX6** and **WT1** genes. *Perlman syndrome* - **Perlman syndrome** is a rare overgrowth disorder associated with an increased risk of **Wilms' tumor**, presenting with macrosomia, visceromegaly, and distinctive facial features. - It is caused by mutations in the **DIS3L2 gene** on chromosome 2q37.

Q: A 6 year old male child presented with deterioration of renal functions. On examination, he is mentally retarded and has got athetosis. There are multiple healed wounds on his body. His mother reassures you that it was as a result of self inflicted injuries. USG showed bilateral renal calculi. Which of the following statements is FALSE regarding the above mentioned condition?

It is an autosomal recessive condition. ***It is an autosomal recessive condition*** - **Lesch-Nyhan syndrome** is an **X-linked recessive disorder**, meaning it primarily affects males and is inherited through the mother. - The gene responsible for **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** deficiency is located on the X chromosome. *Allopurinol may be used in treating the condition* - **Allopurinol** can be used to treat the **hyperuricemia** and prevent **renal calculi** and **gout** in patients with Lesch-Nyhan syndrome. - It works by inhibiting **xanthine oxidase**, thereby reducing uric acid production. *Kelley - Seegmiller syndrome is a milder variant of the condition* - **Kelley-Seegmiller syndrome** is indeed a milder variant of **Lesch-Nyhan syndrome**, characterized by partial rather than complete deficiency of **HGPRT** activity. - Patients with Kelley-Seegmiller syndrome typically present with **hyperuricemia** and **gout-like symptoms** but without the severe neurological manifestations such as **cognitive impairment** and **self-mutilation**. *Hyperuricemia is a characteristic feature of the condition* - **Hyperuricemia** is a hallmark feature of **Lesch-Nyhan syndrome** due to the deficiency of **HGPRT**, leading to overproduction and decreased salvage of purines. - This elevated uric acid level can cause **gouty arthritis** and **renal calculi**, contributing to renal dysfunction. *HGPRT enzyme deficiency is the underlying biochemical defect* - **Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)** deficiency is the fundamental enzyme defect in **Lesch-Nyhan syndrome**. - This enzyme is crucial for the **purine salvage pathway**, and its absence leads to overproduction of uric acid and accumulation of purine precursors that contribute to the neurological manifestations.

Q: Which of the following is not a feature of Turner's syndrome?

Tall stature. ***Tall stature*** - **Tall stature** is a feature of conditions like **Klinefelter syndrome** (XXY), not Turner syndrome. - Individuals with Turner syndrome (monosomy X) typically present with **short stature**, which is one of the most consistent clinical features. *Bicuspid aortic valve* - A **bicuspid aortic valve** is a common cardiovascular anomaly found in individuals with Turner syndrome. - This congenital heart defect can lead to complications such as **aortic stenosis** or **aortic regurgitation**. *External genitalia are normal* - The **external genitalia** of individuals with Turner syndrome are typically **normal** and female in appearance at birth. - However, they experience **gonadal dysgenesis** (streaky ovaries), leading to primary amenorrhea and infertility. *Swelling of nape of neck* - **Swelling of the nape of the neck** is characteristic of Turner syndrome, often presenting as **nuchal folds** or a **webbed neck**. - This is due to **lymphatic malformation** during fetal development. *Cubitus valgus* - **Cubitus valgus** (increased carrying angle of the elbow) is a common skeletal abnormality in Turner syndrome. - This results from abnormal bone development and is present in approximately 50% of individuals with Turner syndrome.

Q: A 22-year-old primigravida notes absent fetal movement for 2 days. The fetus is delivered stillborn at 19 weeks' gestation. The macerated fetus shows marked hydrops fetalis and a large posterior cystic hygroma of the neck. At autopsy, internal anomalies include aortic coarctation and a horseshoe kidney. Which of the following karyotypes is most likely to be present in cells obtained from this fetus?

45, X. ***45, X*** - The combination of **hydrops fetalis**, a large **cystic hygroma**, **aortic coarctation**, and **horseshoe kidney** is highly characteristic of **Turner syndrome (45, X)**. - Turner syndrome is caused by the **absence of an entire X chromosome** in females and often leads to severe developmental anomalies, frequently resulting in stillbirth. *47, XYY* - This karyotype describes **XYY syndrome (Jacob's syndrome)** in males, characterized by an **extra Y chromosome**. - It typically presents with tall stature and normal development, but not the severe fetal anomalies seen in this case. *47, XXY* - This karyotype describes **Klinefelter syndrome** in males, characterized by an **extra X chromosome**. - It typically presents with tall stature, infertility, gynecomastia, and learning difficulties, but not the severe fetal anomalies or early lethality seen in this case. *47, XX, +18* - This karyotype indicates **Trisomy 18 (Edwards syndrome)**, which is associated with various severe congenital malformations. - While some features like **intrauterine growth restriction** and heart defects can be seen, the specific combination of **cystic hygroma** and **aortic coarctation** with hydrops is less classic for Trisomy 18. *47, XX, +21* - This karyotype represents **Trisomy 21 (Down syndrome)**, which is characterized by intellectual disability, distinctive facial features, and cardiac defects. - **Hydrops fetalis** and **cystic hygroma** are rare in Down syndrome, making it an unlikely diagnosis given the complete clinical picture.

Q: Which of the following is a feature of Phenylketonuria?

Intellectual disability. ***Intellectual disability*** - Unmanaged **phenylketonuria (PKU)** leads to a toxic buildup of **phenylalanine** in the brain, causing severe and irreversible **intellectual disability**. - This neurotoxic effect is the primary and most devastating long-term consequence if not diagnosed and treated early. *Seizures* - While seizures can occur in **untreated PKU** due to neurotoxicity, they are a less consistent feature compared to intellectual disability. - Seizures typically occur in the context of severe, untreated disease and are considered a complication rather than a defining diagnostic feature. - Intellectual disability is the more universal and characteristic neuropsychiatric manifestation of PKU. *Loss of deep tendon reflexes* - This is not a typical feature of PKU; patients usually present with **increased muscle tone** and **hyperreflexia** due to neurological damage. - Loss of deep tendon reflexes is more characteristic of certain peripheral neuropathies or disorders affecting lower motor neurons. *Macrocephaly* - **Microcephaly**, rather than macrocephaly, can occasionally be observed in severe, untreated PKU due to impaired brain growth. - Macrocephaly is generally associated with conditions like hydrocephalus or certain genetic syndromes, not PKU. *All of the options* - This option is incorrect because the loss of deep tendon reflexes and macrocephaly are not characteristic features of PKU. - While seizures can occur, intellectual disability is the most defining and consistent feature among the options provided.

Q: What is the typical IQ range for males affected with Fragile X syndrome?

IQ range of 60-80. **IQ range of 60-80** - Males affected with **Fragile X syndrome** typically experience **moderate intellectual disability**, corresponding to an IQ range of 60-80. - This range indicates significant cognitive impairment, yet usually allows for some level of independent living and vocational skills with support. *IQ range of 20-40* - An IQ range of 20-40 represents **severe intellectual disability**, which is less common for the typical presentation of Fragile X syndrome in males. - While some individuals with Fragile X may fall into this range, it is not considered the most typical or average outcome. *IQ range of 50-70* - An IQ range of 50-70 represents **mild to moderate intellectual disability**, which overlaps with but is generally slightly lower than the most typical presentation. - While many males with Fragile X syndrome may score in this range, the typical range cited in literature extends slightly higher to 60-80. *IQ range of 80-100* - An IQ range of 80-100 is considered **borderline to low-average intelligence**, which is generally higher than the typical impact of Fragile X syndrome on male cognitive function. - This range is not indicative of the moderate intellectual disability characteristic of the syndrome. *Normal IQ range (90-110)* - A **normal IQ range (90-110)** is inconsistent with the diagnosis of Fragile X syndrome, which is a leading cause of inherited intellectual disability. - While females with Fragile X may have a wider range of IQs, including normal intelligence, males are typically more severely affected.

Q: Which of the following is true about ataxia telangiectasia?

It is an autosomal recessive disease. ***It is an autosomal recessive disease*** - Ataxia telangiectasia is caused by mutations in the **ATM gene**, which is inherited in an **autosomal recessive** pattern. - This genetic defect leads to a deficiency in a protein crucial for DNA repair, causing systemic effects. *There is absence of amphicytes in different organs* - This statement is incorrect; **ataxia telangiectasia** is not characterized by an absence of amphicytes. - The term "amphicytes" is not typically associated with the defining pathological features of ataxia telangiectasia. *It is associated with normal immune function* - Ataxia telangiectasia is associated with **immunodeficiency**, particularly affecting T- and B-cell function. - Patients often experience recurrent infections due to impaired adaptive immunity, which is not a characteristic of normal immune function. *Serum levels of IgA are increased* - Patients with ataxia telangiectasia typically have **decreased serum levels of IgA**, and often IgG and IgE, leading to immunodeficiency. - Increased IgA levels are characteristic of other conditions and not ataxia telangiectasia. *Serum alpha-fetoprotein levels are decreased* - In ataxia telangiectasia, serum **alpha-fetoprotein (AFP) levels are characteristically elevated**, not decreased. - Elevated AFP is a useful diagnostic marker for this condition.

Question 1

Wilms' tumor associated with all except -

Accepted Answer

Digeorge syndrome

Answer

Beckwith Weidman

Answer

Denys-Drash syndrome

Answer

WAGR

Answer

Perlman syndrome

Question 2

A 6 year old male child presented with deterioration of renal functions. On examination, he is mentally retarded and has got athetosis. There are multiple healed wounds on his body. His mother reassures you that it was as a result of self inflicted injuries. USG showed bilateral renal calculi. Which of the following statements is FALSE regarding the above mentioned condition?

Accepted Answer

It is an autosomal recessive condition

Answer

Allopurinol may be used in treating the condition

Answer

Kelley - Seegmiller syndrome is a milder variant of the condition

Answer

Hyperuricemia is a characteristic feature of the condition

Answer

HGPRT enzyme deficiency is the underlying biochemical defect

Question 3

Which of the following is not a feature of Turner's syndrome?

Accepted Answer

Tall stature

Answer

Bicuspid aortic valve

Answer

External genitalia are normal

Answer

Swelling of nape of neck

Answer

Cubitus valgus

Question 4

A baby boy is brought to the hospital because of convulsions. In the course of workup, his body temperature and plasma glucose are normal, but his CSF glucose is 12 mg/dL. A possible explanation is:

Accepted Answer

GLUT-1 55K deficiency in capillaries

Answer

GLUT-1 45K deficiency in microglia

Answer

GLUT 5 deficiency in cerebral capillaries

Answer

SGLT 1 deficiency in astrocytes

Answer

GLUT-3 deficiency in neurons

Question 5

A 3 year old child develops headaches and is brought to the family doctor. Funduscopic examination reveals papilledema; one retina also shows a very vascular tumor. CT of the head demonstrates a cystic tumor of the cerebellum. This child has a high likelihood of later developing which of the following?

Accepted Answer

Bilateral renal cell carcinoma

Answer

Pheochromocytoma

Answer

Pancreatic neuroendocrine tumor

Answer

Hemangioblastoma of the spinal cord

Answer

Acoustic neuroma

Question 6

A 22-year-old primigravida notes absent fetal movement for 2 days. The fetus is delivered stillborn at 19 weeks' gestation. The macerated fetus shows marked hydrops fetalis and a large posterior cystic hygroma of the neck. At autopsy, internal anomalies include aortic coarctation and a horseshoe kidney. Which of the following karyotypes is most likely to be present in cells obtained from this fetus?

Accepted Answer

45, X

Answer

47, XYY

Answer

47, XX, +18

Answer

47, XX, +21

Answer

47, XXY

Question 7

Which of the following is a feature of Phenylketonuria?

Accepted Answer

Intellectual disability

Answer

Loss of deep tendon reflexes

Answer

All of the options

Answer

Macrocephaly

Answer

Seizures

Question 8

What is the typical IQ range for males affected with Fragile X syndrome?

Accepted Answer

IQ range of 60-80

Answer

IQ range of 20-40

Answer

IQ range of 80-100

Answer

Normal IQ range (90-110)

Answer

IQ range of 50-70

Question 9

Which of the following is true about ataxia telangiectasia?

Accepted Answer

It is an autosomal recessive disease

Answer

There is absence of amphicytes in different organs

Answer

It is associated with normal immune function

Answer

Serum levels of IgA are increased

Answer

Serum alpha-fetoprotein levels are decreased

Question 10

An 8-month-old infant is brought in with poor feeding, lethargy, hypotonia, and hepatomegaly. Labs reveal hypoglycemia and metabolic acidosis. Which condition is most likely?

Accepted Answer

Von Gierke disease

Answer

Hereditary fructose intolerance

Answer

Galactosemia

Answer

Pompe disease

Answer

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

Genetic and Metabolic Disorders — MCQs

Genetic and Metabolic Disorders — MCQs

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