Genetic and Metabolic Disorders — MCQs

A 6-month-old child presented with multiple episodes of seizures over the past 2.5 months. The child was admitted to the ward and had frequent episodes of hypoglycemia, which precipitated the seizures. On examination, hepatosplenomegaly, short stature, thin extremities, and a doll-like facies were noted. Laboratory findings revealed hyperuricemia, lactic acidosis, and hyperlipidemia. Which enzyme deficiency is responsible for this disorder?

Q118

Which of the following is not a usual feature of Noonan syndrome?

Q119

Which condition is primarily associated with an abnormality of the X chromosome?

Q120

A four-year-old child presents with a large face, large jaw, large ears, and macroorchidism. What is the most likely diagnosis?

Genetic and Metabolic Disorders US Medical PG Practice Questions and MCQs

Question 111: What is the inheritance pattern of Crouzon syndrome?

A. Autosomal recessive
B. X-linked recessive
C. Mitochondrial
D. Autosomal dominant (Correct Answer)
E. X-linked dominant

Explanation: ***Autosomal dominant*** - Crouzon syndrome is caused by a mutation in the **FGFR2 gene**, which is inherited in an **autosomal dominant pattern**. - This means only one copy of the mutated gene is needed for an individual to be affected, and there is a 50% chance of passing it to offspring. *Autosomal recessive* - Autosomal recessive conditions require **two copies of the mutated gene** (one from each parent) for the disease to manifest. - While some craniosynostosis syndromes are autosomal recessive, Crouzon syndrome is not. *X-linked recessive* - **X-linked recessive disorders** primarily affect males, as they only have one X chromosome. - Crouzon syndrome affects both males and females equally, ruling out X-linked inheritance. *X-linked dominant* - **X-linked dominant disorders** affect both males and females but often show more severe manifestations in males. - Crouzon syndrome does not follow an X-linked pattern and is not associated with the X chromosome. *Mitochondrial* - **Mitochondrial inheritance** involves genes within the mitochondrial DNA, passed exclusively from the mother to all her children. - This pattern of inheritance does not match the observed transmission of Crouzon syndrome.

Question 112: Simian crease is not seen in which of the following?

A. Trisomy 13
B. Noonan syndrome
C. Down
D. Atopic dermatitis (Correct Answer)
E. Trisomy 18

Explanation: ***Atopic dermatitis*** - **Atopic dermatitis** is a chronic inflammatory skin condition characterized by **eczematous lesions** and **itching**, and does not involve congenital hand abnormalities. - A **Simian crease** (single palmar crease) is a feature associated with certain chromosomal disorders, not skin conditions. *Down* - **Down syndrome** (Trisomy 21) is strongly associated with the presence of a **Simian crease**, along with other distinctive facial and physical features. - This chromosomal anomaly affects development and often results in characteristic dermatoglyphic patterns. *Trisomy 13* - **Trisomy 13** (Patau syndrome) is a severe chromosomal disorder that frequently presents with a **Simian crease** as one of its many congenital abnormalities. - Other features include **polydactyly**, **cleft lip/palate**, and severe intellectual disability. *Trisomy 18* - **Trisomy 18** (Edwards syndrome) is another severe chromosomal disorder commonly associated with a **Simian crease**. - Other features include **clenched fists with overlapping fingers**, **rocker-bottom feet**, and severe intellectual disability. *Noonan syndrome* - While not as classically associated as Down or Trisomy 13, **Noonan syndrome** can sometimes include a **Simian crease** among its varied developmental features. - It is a genetic condition characterized by distinctive facial features, **short stature**, and heart defects, rather than a chromosomal anomaly.

Question 113: A one-year-old child, who was previously normal, is suffering from copious nasal discharge, coarse facial features, a large tongue, a bulging head, and a flattened nose. He is also experiencing an enlarged spleen and liver. What is the most likely diagnosis?

A. Hypothyroidism
B. Proteus syndrome
C. Hurler syndrome (Correct Answer)
D. Beckwith-Wiedemann syndrome
E. Hunter syndrome

Explanation: ***Hurler syndrome*** - Characterized by **mucopolysaccharidosis**, leading to features like **coarse facial features**, **enlarged tongue**, and **bulging head** [1]. - The presence of **hepatosplenomegaly** and respiratory symptoms like nasal discharge aligns well with this metabolic disorder [1]. *Proteus syndrome* - Primarily presents with **overgrowth** of tissues and is often associated with **skin lesions**, which are not described in this case. - Does not typically involve **systemic symptoms** like liver and spleen enlargement or respiratory distress as seen here. *Hypothyroidism* - Would lead to **growth retardation** and features like **dry skin** or **goiter**, but not the **coarse facial features** or nasopharyngeal symptoms. - Cannot satisfactorily explain the **hepatosplenomegaly** and characteristic facial features present in this child. *Beckwith widman syndrome* - Mainly marked by **organomegaly**, **macroglossia**, and **abdominal wall defects**, but coarse features is not a significant finding. - The symptoms of **respiratory distress** and facial changes do not correlate with this syndrome's typical presentation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 163-164.

Question 114: All of the following are seen in RASopathies except which of the following?

A. Sparse curly hair
B. Distinct craniofacial features
C. Keratosis pilaris
D. Desquamation of skin (Correct Answer)
E. Palmoplantar hyperkeratosis

Explanation: ***Desquamation of skin*** - **Desquamation (skin peeling)** is generally not considered a characteristic feature of RASopathies. - While various skin issues can occur, widespread desquamation is more typical of other conditions like **ichthyosis** or severe inflammatory dermatoses. - This is the **correct answer** as it is NOT typically seen in RASopathies. *Sparse curly hair* - **Sparse, curly, or unruly hair** is a common dermatological finding across various RASopathies, including **Noonan syndrome** and **Costello syndrome**. - It results from the dysregulation of the **RAS/MAPK signaling pathway**, which plays a crucial role in hair follicle development. *Distinct craniofacial features* - Many RASopathies are characterized by **distinct craniofacial dysmorphisms**, such as broad forehead, hypertelorism, downward-slanting palpebral fissures, and low-set ears. - These features vary between specific syndromes (e.g., **Noonan syndrome**, **Costello syndrome**, **CFC syndrome**) but are a hallmark of the group. *Keratosis pilaris* - **Keratosis pilaris**, characterized by small, rough bumps (often on the upper arms, thighs, and buttocks), is a frequently observed dermatologic manifestation in several RASopathies. - It is thought to be related to the underlying **RAS/MAPK pathway dysfunction**, which influences keratinization and follicular development. *Palmoplantar hyperkeratosis* - **Palmoplantar hyperkeratosis** (thickening of skin on palms and soles) is a prominent feature of **Costello syndrome**, one of the RASopathies. - It typically develops in early childhood and is considered a characteristic dermatologic manifestation of this condition. - This feature helps distinguish Costello syndrome from other RASopathies.

Question 115: An infant with intolerance to breast milk, vomiting, and diarrhea develops cataracts. Which of the following is the most likely diagnosis?

A. Galactosemia (Correct Answer)
B. Fabry disease
C. Lowe syndrome
D. Congenital hypoglycemia
E. Homocystinuria

Explanation: **Galactosemia** - **Galactosemia** is an inborn error of metabolism where the body is unable to process **galactose**, leading to its build-up. - Symptoms such as **vomiting**, **diarrhea**, **failure to thrive** (intolerance to breast milk containing lactose, which is broken down into glucose and galactose), and **cataracts** are classic signs of galactosemia in infants. *Lowe syndrome* - Also known as **oculocerebrorenal syndrome**, Lowe syndrome is an X-linked disorder characterized by **congenital cataracts**, **renal tubular dysfunction**, and **intellectual disability**. - While cataracts are present, it primarily presents with **kidney and brain abnormalities**, not predominantly with GI symptoms like vomiting and diarrhea upon feeding. *Fabry disease* - **Fabry disease** is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme **alpha-galactosidase A**. - It is characterized by **neuropathic pain**, **angiokeratomas**, **renal disease**, and **cardiac involvement**, and is not typically associated with infantile vomiting, diarrhea, or early onset cataracts from breast milk intolerance. *Homocystinuria* - **Homocystinuria** is an inherited disorder of methionine metabolism due to **cystathionine beta-synthase deficiency**. - It presents with **lens dislocation** (ectopia lentis), **intellectual disability**, **skeletal abnormalities** (marfanoid habitus), and **thromboembolism**, typically becoming apparent in later infancy or childhood, not with acute feeding intolerance and GI symptoms in early infancy. *Congenital hypoglycemia* - **Congenital hypoglycemia** refers to abnormally low blood glucose levels at birth or shortly after. - Symptoms include **poor feeding**, **lethargy**, **irritability**, and **seizures**, but it is not typically associated with cataracts or specific intolerance to breast milk causing vomiting and diarrhea as seen in metabolic disorders.

Question 116: If a baby has a XX or XY genotype, normal internal gonads, but ambiguous external genitalia, it is called?

A. True hermaphrodite
B. Disorder of Sex Development (DSD) (Correct Answer)
C. Intersex (outdated term)
D. Any of the above
E. Pseudohermaphrodite

Explanation: ***Disorder of Sex Development (DSD)*** - This is the **current preferred medical terminology** that encompasses conditions where there is a discrepancy between chromosomal sex, gonadal sex, and anatomical sex. - The scenario described—normal XX or XY genotype and normal internal gonads with **ambiguous external genitalia**—fits the definition of a DSD. - This **umbrella term** has replaced older terminology and is the most appropriate answer in modern medical practice. *True hermaphrodite* - A true hermaphrodite, now referred to as **ovotesticular DSD**, possesses both ovarian and testicular tissue simultaneously. - The question specifies **normal internal gonads** (either ovaries or testes, not both), which excludes this diagnosis. *Intersex (outdated term)* - While "intersex" was historically used to describe individuals with atypical sexual characteristics, it is now considered an **outdated and less precise** term in medical contexts. - "Disorder of Sex Development" is the preferred and more comprehensive medical classification. *Pseudohermaphrodite* - This was the **classical medical term** for exactly this presentation: normal chromosomal sex and appropriate internal gonads but ambiguous external genitalia. - Examples include 46,XX DSD with virilization (e.g., **congenital adrenal hyperplasia**) or 46,XY DSD with undervirilization (e.g., **androgen insensitivity syndrome**). - This term has been **replaced by DSD terminology** in modern medical practice to avoid stigmatizing language. *Any of the above* - While multiple terms have been used historically, **DSD is the most accurate and currently accepted medical term** for this specific presentation. - Therefore, this option is incorrect as it suggests all answers are equally valid.

Question 117: A 6-month-old child presented with multiple episodes of seizures over the past 2.5 months. The child was admitted to the ward and had frequent episodes of hypoglycemia, which precipitated the seizures. On examination, hepatosplenomegaly, short stature, thin extremities, and a doll-like facies were noted. Laboratory findings revealed hyperuricemia, lactic acidosis, and hyperlipidemia. Which enzyme deficiency is responsible for this disorder?

A. Glucose-6-phosphatase (Correct Answer)
B. Acid maltase
C. Phosphofructokinase deficiency
D. Debranching enzyme deficiency
E. Branching enzyme

Explanation: ***Glucose-6-phosphatase*** - This enzyme deficiency leads to **Von Gierke's disease (Type I glycogen storage disease)**, characterized by severe **fasting hypoglycemia** due to the inability to release glucose from glycogen stores or perform gluconeogenesis. - The accumulation of glucose-6-phosphate shunts substrates towards **lactic acid**, **uric acid**, and **lipid** synthesis, explaining the **lactic acidosis, hyperuricemia, hyperlipidemia**, and resultant **hepatosplenomegaly** and **doll-like facies**. *Acid maltase* - This refers to **Pompe disease (Type II glycogen storage disease)**, which primarily affects **cardiac and skeletal muscles**, leading to **cardiomyopathy** and muscle weakness. - While it involves glycogen storage, **hypoglycemia** and the metabolic derangements seen in the patient (e.g., hyperuricemia, lactic acidosis) are **not characteristic features**. *Phosphofructokinase deficiency* - This is **Tarui disease (Type VII glycogen storage disease)**, a rare disorder affecting **muscle and red blood cells**, causing **exercise intolerance**, muscle pain, and hemolytic anemia. - While it affects glycolysis, it **does not typically present with severe hypoglycemia** or the specific metabolic characteristics like hyperuricemia and lactic acidosis noted in the child. *Debranching enzyme deficiency* - This is **Cori disease (Type III glycogen storage disease)**, which results in milder hypoglycemia, hepatomegaly, and myopathy. - The deficiency leads to the accumulation of **glycogen with short outer branches**, but the severe and persistent metabolic derangements (marked lactic acidosis, hyperuricemia) and consistent severe hypoglycemia described are **less characteristic** than in Von Gierke's disease. *Branching enzyme* - This is **Andersen disease (Type IV glycogen storage disease)**, a rare disorder characterized by **progressive liver cirrhosis** and **hepatosplenomegaly** starting in infancy. - Unlike Von Gierke's disease, it **does not present with hypoglycemia** as the primary feature, and the metabolic profile (hyperuricemia, lactic acidosis, hyperlipidemia) is **not typical**.

Question 118: Which of the following is not a usual feature of Noonan syndrome?

A. Webbed neck
B. Short stature
C. Infertility
D. Intellectual disability (Correct Answer)
E. Pulmonary stenosis

Explanation: ***Intellectual disability*** - While some individuals with **Noonan syndrome** may have mild learning difficulties, **significant intellectual disability** is not a typical or defining feature of the condition. - The spectrum of cognitive abilities in Noonan syndrome ranges from normal to mild learning challenges. *Webbed neck* - A **webbed neck** due to excess skin folds is a common dysmorphic feature in Noonan syndrome, similar to Turner syndrome. - This is an important diagnostic clue, contributing to the characteristic gestalt of the syndrome. *Infertility* - Both males and females with Noonan syndrome can experience **infertility** or subfertility, often due to gonadal dysfunction such as **cryptorchidism** in males and ovarian insufficiency in females. - **Cryptorchidism** (undescended testes) is particularly common and can impact fertility. *Short stature* - **Short stature** is a very common and characteristic feature of Noonan syndrome, often evident from childhood. - Growth hormone deficiency can contribute to the growth failure seen in these individuals. *Pulmonary stenosis* - **Pulmonary stenosis** is the most common cardiac defect in Noonan syndrome, occurring in approximately **50-60%** of affected individuals. - Other cardiac abnormalities may include hypertrophic cardiomyopathy and atrial septal defects.

Question 119: Which condition is primarily associated with an abnormality of the X chromosome?

A. Turner's syndrome (Correct Answer)
B. Edward syndrome
C. Patau syndrome
D. Klinefelter syndrome
E. Down syndrome

Explanation: ***Turner's syndrome*** - **Turner's syndrome** is a genetic condition caused by the **absence of all or part of one X chromosome** in females (45, XO). - This X chromosome abnormality leads to characteristics such as **short stature**, ovarian dysgenesis, and a webbed neck. *Edward syndrome* - **Edward syndrome** is caused by the presence of an extra copy of chromosome 18 (trisomy 18), not an X chromosome abnormality. - It is associated with severe developmental delays, micrognathia, and **rocker-bottom feet**. *Patau syndrome* - **Patau syndrome** results from an extra copy of chromosome 13 (trisomy 13), not an abnormality of the X chromosome. - It is characterized by severe intellectual disability, **cleft lip and palate**, and polydactyly. *Down syndrome* - **Down syndrome** is caused by an extra copy of chromosome 21 (trisomy 21), not an X chromosome abnormality. - It is the most common chromosomal disorder, characterized by intellectual disability, **characteristic facial features**, and increased risk of congenital heart defects. *Klinefelter syndrome* - **Klinefelter syndrome** is a genetic condition in males with an extra X chromosome (47, XXY), which is an X chromosome abnormality, but it is not the **primary** condition *exclusively* associated with an X abnormality among the given choices, as Turner's is due to a *missing* X chromosome. - This condition leads to characteristics such as **tall stature**, underdeveloped testes, and gynecomastia.

Question 120: A four-year-old child presents with a large face, large jaw, large ears, and macroorchidism. What is the most likely diagnosis?

A. Down syndrome
B. Cri du chat syndrome
C. Fragile X syndrome (Correct Answer)
D. McCune-Albright syndrome
E. Klinefelter syndrome

Explanation: ***Fragile X syndrome*** - This syndrome is characterized by **macroorchidism** (enlarged testes) and distinct facial features such as a **large face**, **prominent jaw**, and **large ears**. - It is an X-linked dominant disorder caused by a **FMR1 gene mutation** leading to an increased number of CGG trinucleotide repeats. *Down syndrome* - Characterized by **upslanting palpebral fissures**, **epicanthic folds**, a **flat nasal bridge**, and a **single palmar crease**, which are not described here. - While associated with intellectual disability, it does not present with macroorchidism or the specific facial features mentioned. *Cri du chat syndrome* - This syndrome is known for a distinctive **high-pitched cry** resembling a cat's meow in infancy, along with **microcephaly** and **hypertelorism**. - It results from a deletion on the **short arm of chromosome 5** and does not typically present with macroorchidism or a large jaw. *McCune-Albright syndrome* - This syndrome is characterized by a triad of **fibrous dysplasia of bone**, **café-au-lait spots** (irregularly shaped hyperpigmented skin lesions), and **precocious puberty**. - It is caused by a somatic mutation in the **GNAS gene** and does not involve the specific facial features or macroorchidism described. *Klinefelter syndrome* - This syndrome (47,XXY) presents with **tall stature**, **gynecomastia**, and **small, firm testes** (not macroorchidism), typically noted after puberty. - Patients may have mild developmental delay but lack the distinctive facial features (large jaw, large ears) seen in this case.

Practice by Chapter

Chromosomal Disorders

Practice Questions

Disorders of Amino Acid Metabolism

Practice Questions

Disorders of Carbohydrate Metabolism

Practice Questions

Disorders of Lipid Metabolism

Practice Questions

Genetic Counseling

Practice Questions

Genetic Testing in Pediatrics

Practice Questions

Inborn Errors of Metabolism

Practice Questions

Lysosomal Storage Diseases

Practice Questions

Mitochondrial Disorders

Practice Questions

Multifactorial Inheritance Disorders

Practice Questions

Newborn Screening

Practice Questions

Single Gene Disorders

Practice Questions

Want unlimited practice?

Get full access to all questions, explanations, and performance tracking.

Start For Free