Genetic and Metabolic Disorders — MCQs

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?

Q23

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

Q24

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:

Q25

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?

Q26

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?

Q27

Which of the following is a feature of Phenylketonuria?

Q28

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

Q29

Which of the following is true about ataxia telangiectasia?

Q30

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?

Genetic and Metabolic Disorders US Medical PG Practice Questions and MCQs

Question 21: Wilms' tumor associated with all except -

A. Beckwith Weidman
B. Denys-Drash syndrome
C. Digeorge syndrome (Correct Answer)
D. WAGR
E. Perlman syndrome

Explanation: ***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.

Question 22: 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?

A. Allopurinol may be used in treating the condition
B. Kelley - Seegmiller syndrome is a milder variant of the condition
C. Hyperuricemia is a characteristic feature of the condition
D. It is an autosomal recessive condition (Correct Answer)
E. HGPRT enzyme deficiency is the underlying biochemical defect

Explanation: ***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.

Question 23: Which of the following is not a feature of Turner's syndrome?

A. Bicuspid aortic valve
B. External genitalia are normal
C. Swelling of nape of neck
D. Tall stature (Correct Answer)
E. Cubitus valgus

Explanation: ***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.

Question 24: 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:

A. GLUT-1 45K deficiency in microglia
B. GLUT 5 deficiency in cerebral capillaries
C. SGLT 1 deficiency in astrocytes
D. GLUT-1 55K deficiency in capillaries (Correct Answer)
E. GLUT-3 deficiency in neurons

Explanation: ***GLUT-1 55K deficiency in capillaries*** - A CSF glucose of 12 mg/dL with normal plasma glucose strongly suggests a problem with **glucose transport across the blood-brain barrier (BBB)**. - The **GLUT-1 isoform (55K)** is the primary glucose transporter responsible for moving glucose from the blood into the brain across the **endothelial cells of the capillaries**, and its deficiency leads to profoundly low CSF glucose, causing seizures. *GLUT-1 45K deficiency in microglia* - The **GLUT-1 45K isoform** is found primarily on **astrocytes** and **neurons** in the brain, and while critical for neuronal glucose uptake, its deficiency alone would not cause such a profound drop in CSF glucose unless the 55K isoform in capillaries was also affected. - **Microglia** primarily express GLUT-5 and GLUT-3, but their function is not the primary determinant of CSF glucose levels. *GLUT 5 deficiency in cerebral capillaries* - **GLUT-5** is primarily a **fructose transporter** and is not the main glucose transporter in the brain or at the blood-brain barrier. - Its deficiency would not significantly impact **glucose transport** into the CSF. *GLUT-3 deficiency in neurons* - **GLUT-3** is the primary neuronal glucose transporter and is critical for neuronal metabolism. - However, GLUT-3 deficiency would affect **intracellular neuronal glucose uptake** rather than glucose transport across the BBB, so CSF glucose levels would remain normal while neurons might be energy-deprived. - The key finding of **low CSF glucose** indicates a problem at the **capillary level** (BBB), not at the neuronal uptake level. *SGLT 1 deficiency in astrocytes* - **SGLT1 (Sodium-Glucose Linked Transporter 1)** is an active glucose transporter primarily found in the **intestine** and **kidney**, and in some cells of the brain but not as the primary glucose transporter for the BBB. - Astrocytes primarily use **GLUT-1 (45K isoform)** for glucose uptake, not SGLT1, or for transport across capillaries.

Question 25: 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?

A. Pheochromocytoma
B. Pancreatic neuroendocrine tumor
C. Bilateral renal cell carcinoma (Correct Answer)
D. Hemangioblastoma of the spinal cord
E. Acoustic neuroma

Explanation: ***Bilateral renal cell carcinoma*** - The presentation of a **cerebellar cystic tumor** with **retinal hemangioblastoma** (vascular tumor) is highly suggestive of **Von Hippel-Lindau (VHL) disease**. - **VHL disease** is an autosomal dominant disorder that significantly increases the risk of developing **bilateral renal cell carcinoma**, which is a common and serious manifestation. - Renal cell carcinoma occurs in approximately **70% of VHL patients** and is a leading cause of mortality, making surveillance critical. *Pheochromocytoma* - While **pheochromocytomas** can be associated with VHL disease (10-20% of cases), they are less common than renal cell carcinoma and typically present with symptoms of catecholamine excess, which are not mentioned here. - VHL disease primarily involves a wide range of tumors, with **renal cell carcinoma** being a major concern later in life for affected individuals. *Pancreatic neuroendocrine tumor* - **Pancreatic neuroendocrine tumors** are also a recognized feature of VHL syndrome but are less common and typically present later in adulthood. - The most significant life-threatening concern in children and young adults with VHL is often the development of **renal cell carcinoma** and central nervous system hemangioblastomas. *Hemangioblastoma of the spinal cord* - **Spinal cord hemangioblastomas** are indeed part of the VHL disease spectrum (25% of cases), but this option lists another manifestation of VHL, whereas the question asks for a high likelihood of *later* developing *which of the following*, implying a major associated systemic malignancy often seen in VHL patients. - While spinal cord hemangioblastomas are common, **renal cell carcinoma** is a major systemic malignancy that poses a significant long-term risk for VHL patients and is often the focus of surveillance. *Acoustic neuroma* - **Acoustic neuromas** (vestibular schwannomas) are **NOT associated with VHL disease**; they are a hallmark feature of **Neurofibromatosis Type 2 (NF2)**, not VHL. - VHL is characterized by hemangioblastomas (CNS and retina), renal cell carcinoma, pheochromocytomas, and pancreatic tumors—not schwannomas.

Question 26: 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?

A. 47, XYY
B. 45, X (Correct Answer)
C. 47, XX, +18
D. 47, XX, +21
E. 47, XXY

Explanation: ***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.

Question 27: Which of the following is a feature of Phenylketonuria?

A. Loss of deep tendon reflexes
B. All of the options
C. Macrocephaly
D. Intellectual disability (Correct Answer)
E. Seizures

Explanation: ***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.

Question 28: What is the typical IQ range for males affected with Fragile X syndrome?

A. IQ range of 20-40
B. IQ range of 60-80 (Correct Answer)
C. IQ range of 80-100
D. Normal IQ range (90-110)
E. IQ range of 50-70

Explanation: **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.

Question 29: Which of the following is true about ataxia telangiectasia?

A. There is absence of amphicytes in different organs
B. It is an autosomal recessive disease (Correct Answer)
C. It is associated with normal immune function
D. Serum levels of IgA are increased
E. Serum alpha-fetoprotein levels are decreased

Explanation: ***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 30: 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?

A. Hereditary fructose intolerance
B. Galactosemia
C. Pompe disease
D. Von Gierke disease (Correct Answer)
E. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

Explanation: ***Von Gierke disease*** - **Type I glycogen storage disease** (GSD I) typically presents in infancy with **hypoglycemia** (due to impaired glucose release from glycogen), **hepatomegaly** (due to glycogen accumulation), and **lactic acidosis**. - Other common findings include **hyperlipidemia** and **hyperuricemia**, while **hypotonia** and **poor feeding** are generalized symptoms stemming from metabolic derangements. *Hereditary fructose intolerance* - This condition presents when **fructose** is introduced into the diet, typically after 4-6 months of age, with symptoms like **nausea, vomiting, abdominal pain**, and **hepatomegaly**. - While it can cause **hypoglycemia** and **metabolic acidosis**, the profound **hypotonia** and general metabolic collapse described in an 8-month-old on a typical diet makes GSD I more likely initially. *Galactosemia* - Symptoms usually appear within days or weeks of birth upon the initiation of **milk feeding**, including **vomiting, lethargy, poor feeding, jaundice, hepatomegaly**, and **cataracts**. - While it causes **hypoglycemia** and can lead to acidosis and hypotonia, the age of presentation and lack of specific mention of jaundice or cataracts makes it a less precise fit. *Pompe disease* - Also known as **glycogen storage disease type II**, it is characterized by the accumulation of glycogen in **lysosomes**, primarily affecting muscles. - The infantile form presents with severe **cardiomyopathy**, **muscle weakness**, and **hypotonia**, but **hypoglycemia** and **hepatomegaly** are not its primary or most prominent features. *Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency* - A **fatty acid oxidation disorder** that presents with episodic **hypoglycemia** (particularly during fasting or illness), **lethargy**, and **hepatomegaly**. - Key distinguishing features include **hypoketotic hypoglycemia** and elevated **dicarboxylic acids** on urine organic acids, but the **lactic acidosis** and overall metabolic profile are more consistent with GSD I.

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Chromosomal Disorders

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Disorders of Amino Acid Metabolism

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Disorders of Carbohydrate Metabolism

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Disorders of Lipid Metabolism

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Genetic Counseling

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Genetic Testing in Pediatrics

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Inborn Errors of Metabolism

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Lysosomal Storage Diseases

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Mitochondrial Disorders

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Multifactorial Inheritance Disorders

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Newborn Screening

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Single Gene Disorders

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