Genetic and Metabolic Disorders Practice Questions

Q: An 8-year-old child with recurrent respiratory infections and growth retardation has a sweat test showing high chloride levels. What is the likely diagnosis?

Cystic fibrosis. ***Cystic fibrosis*** - The combination of **recurrent respiratory infections**, **growth retardation**, and **high chloride levels in a sweat test** is pathognomonic for cystic fibrosis. - This genetic disorder primarily affects chloride transport, leading to thick, viscous secretions that obstruct airways and impact nutrient absorption. *Primary ciliary dyskinesia* - This condition is characterized by **recurrent respiratory infections** due to dysfunctional cilia, but it does **not typically present with growth retardation** or elevated sweat chloride. - Diagnosis involves **ciliary ultrastructure analysis** or genetic testing, not a sweat test. *Asthma* - Asthma is a chronic inflammatory airway disease causing **wheezing, cough, and shortness of breath**, often triggered by allergens or exercise. - It does **not involve growth retardation or elevated sweat chloride levels**, and respiratory infections are not typically recurrent as a primary feature. *Bronchiectasis* - Bronchiectasis involves **permanent dilatation of the bronchi** due to chronic inflammation and infection, leading to recurrent respiratory infections and chronic cough. - While it can be a complication of cystic fibrosis, **isolated bronchiectasis does not explain the growth retardation or positive sweat test** in the absence of an underlying condition. *Immunodeficiency disorder* - While immunodeficiency can cause **recurrent respiratory infections** and potentially growth retardation, it does **not cause elevated sweat chloride levels**. - Diagnosis involves **immunoglobulin levels, lymphocyte counts, and specific immune function tests**, not a sweat test.

Q: An infant with a suspected metabolic disorder has abnormal newborn screening results. What is the most appropriate next step to confirm the diagnosis?

Conduct a comprehensive metabolic panel. ***Conduct a comprehensive metabolic panel*** - Abnormal newborn screen results for metabolic disorders are **presumptive** diagnoses and require prompt **confirmatory testing**. - A comprehensive metabolic panel, including **amino acid analysis**, **organic acid analysis**, and **acylcarnitine profile**, can pinpoint the specific metabolic defect. *Repeat the newborn screening* - While sometimes done for minor abnormalities or sample issues, repeating the newborn screen delays definitive diagnosis and intervention in cases of **significant abnormalities**. - **Confirmatory tests** provide more detailed and specific information than a repeat screen. *Start dietary modifications based on the most likely diagnosis* - Initiating dietary changes before a definitive diagnosis is made can be **harmful** if the suspected diagnosis is incorrect or if the specific metabolic pathway affected is not fully understood. - **Nutritional intervention** for metabolic disorders is often very specific and requires confirmation. *Obtain a detailed three-generation family history* - A family history is an important part of the evaluation but is **not a confirmatory diagnostic test** for a suspected metabolic disorder in an affected infant. - While it can guide further testing or provide information about inheritance patterns, it does not directly identify the metabolic abnormality. *Refer to genetics specialist without further testing* - While genetics referral is important for long-term management and counseling, it should not precede **confirmatory diagnostic testing**. - Definitive diagnosis is needed to guide immediate management and to provide the specialist with specific information for targeted counseling.

Q: Which genetic disorder is characterized by a deletion on chromosome 22 and includes features such as thymic hypoplasia and hypocalcemia?

DiGeorge syndrome. ***DiGeorge syndrome*** - This syndrome is characterized by a **microdeletion on chromosome 22q11.2**, leading to developmental abnormalities. - Key features include **thymic hypoplasia ( T-cell immunodeficiency )**, **parathyroid hypoplasia (hypocalcemia)**, **congenital heart defects**, and distinctive facial features. *Down syndrome* - Caused by an extra copy of **chromosome 21 (trisomy 21)**, not a deletion on chromosome 22. - Characterized by intellectual disability, characteristic facial features, and increased risk of **congenital heart disease** and **leukemia**, not specifically thymic hypoplasia or hypocalcemia. *Turner syndrome* - Results from the absence of all or part of one **X chromosome (45, X0)**, affecting only females. - Presents with short stature, webbed neck, and **gonadal dysgenesis**, without the characteristic features of DiGeorge syndrome. *Klinefelter syndrome* - Characterized by an extra **X chromosome in males (47, XXY)**. - Typically presents with **infertility**, small testes, and gynecomastia, without a deletion on chromosome 22 or the specific clinical features mentioned. *Williams syndrome* - Caused by a **microdeletion on chromosome 7q11.23**, not chromosome 22. - Features include distinctive **"elfin" facial features**, **supravalvular aortic stenosis**, hypercalcemia (not hypocalcemia), and an overly friendly personality, without thymic hypoplasia.

Q: A 6-month-old infant presents with failure to thrive and developmental delays. Serum laboratory results show elevated liver enzymes and bilirubin. What is the most likely diagnosis?

Biliary atresia. ***Biliary atresia*** - This is the **most likely diagnosis** in a 6-month-old infant with **failure to thrive**, **elevated liver enzymes**, and **elevated bilirubin**. - Biliary atresia presents with **progressive conjugated hyperbilirubinemia** starting in the first 2-8 weeks of life, with **persistent jaundice**, **hepatomegaly**, and eventual **cirrhosis** if untreated. - Classic triad: **jaundice**, **acholic stools**, and **dark urine**, though not all features may be explicitly reported. - The **age of presentation** (6 months) and constellation of findings make this the most characteristic diagnosis. *Alpha-1 antitrypsin deficiency* - Can cause **neonatal hepatitis syndrome** with cholestasis, elevated transaminases, and conjugated hyperbilirubinemia. - However, the presentation is typically **earlier** (within first 2 months) and many infants are **asymptomatic** or have milder disease. - More commonly associated with **emphysema in adults** rather than isolated hepatic presentation in infancy. *Hepatitis* - Viral hepatitis can cause **elevated liver enzymes** and **bilirubin**. - However, isolated viral hepatitis as the primary cause of **chronic failure to thrive** and **developmental delays** over 6 months is less likely than structural/metabolic causes. - Would typically have more **acute presentation** or history of exposure. *Galactosemia* - Presents with **vomiting**, **jaundice**, **hepatomegaly**, **cataracts**, and **E. coli sepsis** in neonates. - Symptoms appear within **days to weeks of birth** upon initiation of milk feeding, not at 6 months. - Would be detected earlier through **newborn screening** in most developed countries. *Wilson disease* - Typically presents in **older children** (>5 years) and **adolescents**, not at 6 months. - Characterized by **copper accumulation** causing hepatic and neurological symptoms, **Kayser-Fleischer rings**. - Age of presentation makes this diagnosis extremely unlikely.

Q: A 5-year-old girl presents with new-onset seizures, developmental delay, and hypopigmented macules on the skin. What is the most likely diagnosis?

Tuberous sclerosis. ***Tuberous sclerosis*** - The classic triad of **seizures**, **developmental delay**, and **hypopigmented macules** (ash-leaf spots) is highly characteristic of tuberous sclerosis complex (TSC). - TSC is a **neurocutaneous disorder** with multisystem involvement, including brain tumors (subependymal giant cell astrocytomas), renal angiomyolipomas, and cardiac rhabdomyomas. *Neurofibromatosis type 1* - Characterized by **café-au-lait spots**, **axillary/inguinal freckling**, and **neurofibromas**. - While seizures and developmental delay can occur, **hypopigmented macules** are not a primary dermatological feature. *Sturge-Weber syndrome* - Identified by a characteristic **port-wine stain** (facial cutaneous angioma) in the distribution of the trigeminal nerve. - Associated with **leptomeningeal angiomas** (leading to seizures) and **ocular abnormalities** like glaucoma, but not hypopigmented macules. *Von Hippel-Lindau disease* - A rare genetic disorder predisposing to tumors in multiple organs, including **hemangioblastomas** of the central nervous system and retina, and **renal cell carcinoma**. - It does not typically present with skin lesions, seizures, or developmental delay in the same way as TSC. *Rett syndrome* - An X-linked genetic disorder causing **developmental regression** (especially loss of purposeful hand movements) and **seizures**, primarily affecting females. - However, it does not present with the characteristic **hypopigmented macules** seen in TSC, and regression typically begins after 6-18 months of normal development.

Q: Identify the best treatment to prevent complications in a newborn diagnosed with phenylketonuria (PKU).

Low-phenylalanine diet. ***Low-phenylalanine diet*** - PKU is caused by a deficiency in the enzyme **phenylalanine hydroxylase**, leading to a buildup of **phenylalanine** in the blood. - A **low-phenylalanine diet** restricts the intake of this amino acid, preventing its accumulation and subsequent neurotoxic effects, thus averting severe complications like **intellectual disability** and seizures. *High-protein diet* - A high-protein diet would be detrimental for a newborn with PKU as it would significantly **increase phenylalanine intake**, exacerbating the metabolic disorder. - High protein intake would lead to greater accumulation of **phenylalanine**, resulting in more severe neurological damage. *Gluten-free diet* - A gluten-free diet is indicated for conditions like **celiac disease** or **gluten sensitivity**, which are unrelated to the metabolic defect in PKU. - While some dietary restrictions may overlap, a gluten-free diet does not specifically address the **phenylalanine metabolism** issue in PKU. *Ketogenic diet* - A ketogenic diet is typically used to manage certain types of **epilepsy** or metabolic disorders involving carbohydrate metabolism. - It does not directly target the **phenylalanine accumulation** that is central to PKU pathophysiology and would not be an effective primary treatment. *Enzyme replacement therapy* - While enzyme replacement therapy is effective for some metabolic disorders (e.g., **Gaucher disease**, **Fabry disease**), it is not the standard treatment for PKU. - The primary management of PKU relies on **dietary restriction** of phenylalanine rather than enzyme supplementation, though pegvaliase (an enzyme substitution therapy) may be used in some adult cases with uncontrolled phenylalanine levels.

Q: What is the current term used to refer to Down syndrome?

Trisomy 21. ***Trisomy 21*** - This is the **current scientific and cytogenetic term** for Down syndrome, indicating the presence of an **extra copy of chromosome 21**. - It is the most accurate and precise term describing the **genetic basis** of the condition and is universally used in medical literature. - While "Down syndrome" remains the clinical name, **Trisomy 21** is the preferred term in genetic and diagnostic contexts. *Oligophrenia* - This is an **outdated and pejorative term** for intellectual disability, no longer used in medical or scientific contexts. - It was a general term for conditions with **significantly impaired intellectual development** but has been abandoned. *Mental retardation* - This term was historically used to describe conditions of cognitive impairment but has been **replaced by "intellectual disability"** due to its stigmatizing connotations. - It is **no longer acceptable** in modern medical terminology. *Intellectual disability* - This is the **current preferred term** for describing cognitive impairment, but it refers to the **functional consequence** of Down syndrome, not the condition itself. - While accurate for describing the cognitive aspects, **Trisomy 21** is the specific genetic diagnostic term. *Mongolism* - This is an **obsolete and offensive term** that was historically used for Down syndrome based on perceived facial features. - It has been completely **abandoned** due to its racist and pejorative nature and should never be used.

Q: Which of the following is a common feature of Down's syndrome?

Hypotonia. ***Hypotonia*** - **Generalized muscle hypotonia** (floppiness) is a hallmark feature present in nearly all individuals with Down syndrome from birth, persisting into childhood and contributing to developmental delays. - This **reduced muscle tone** is universally observed and affects motor development, posture, and feeding in infants with Down syndrome. *Congenital heart defects* - **Congenital heart defects**, particularly **atrioventricular septal defects**, are very common in Down syndrome, affecting 40-60% of individuals. - While highly prevalent, these are not universally present in all cases, unlike hypotonia which is nearly always observed. *Single palmar crease* - A **single transverse palmar crease** (simian crease) is present in approximately 45% of individuals with Down syndrome. - While common, it is not universally present and can also occur in 1-2% of the general population, making it less specific than hypotonia. *Female infertility* - **Female fertility** in Down syndrome is reduced but not universally absent; some women with Down syndrome can conceive, though there is an increased risk of miscarriage and having a child with Down syndrome. - **Male infertility** is more pronounced, with most males having impaired spermatogenesis. *Early onset Alzheimer's disease* - Individuals with Down syndrome have a high risk of developing **early-onset Alzheimer's disease** due to triplication of the APP gene on chromosome 21, but this is a later-life complication, not an early or defining feature. - This **neurological complication** typically manifests in the 40s or 50s, affecting cognition and daily functioning progressively.

Q: Which of the following is true regarding Turner's syndrome?

Monosomy of the X chromosome. ***Monosomy of the X chromosome*** - Turner's syndrome is a **chromosomal disorder** characterized by the presence of only one complete X chromosome (45,X) in females, instead of the usual two. - This **monosomy X** is the **fundamental genetic defect** that defines Turner's syndrome and is the underlying cause of all clinical features. - This is the **most definitive answer** as it represents the core diagnostic criterion. *Conductive hearing loss* - While girls with Turner's syndrome can have hearing problems, they more commonly experience **sensorineural hearing loss** or recurrent otitis media. - Conductive hearing loss is not a primary or characteristic feature of Turner's syndrome. *Autosomal recessive inheritance* - Turner's syndrome is a **chromosomal abnormality** (monosomy X), not an autosomal recessive genetic disorder. - Its occurrence is typically **sporadic** due to nondisjunction during meiosis, not inherited in a Mendelian fashion. *Increased carrying angle of the elbow (cubitus valgus)* - Cubitus valgus **is indeed a true characteristic feature** of Turner's syndrome and is commonly seen in affected individuals. - However, while clinically important, it is a **secondary physical manifestation** resulting from the underlying chromosomal abnormality. - The **monosomy of the X chromosome is the more fundamental answer** as it is the genetic basis for all features, including cubitus valgus. *Transmitted through maternal inheritance* - Turner's syndrome occurs **sporadically** due to random nondisjunction events during gamete formation. - It is **not transmitted** through maternal or paternal inheritance patterns. - Each occurrence is typically a de novo event, not passed from parent to child.

Question 1

An 8-year-old child with recurrent respiratory infections and growth retardation has a sweat test showing high chloride levels. What is the likely diagnosis?

Accepted Answer

Cystic fibrosis

Answer

Primary ciliary dyskinesia

Answer

Asthma

Answer

Bronchiectasis

Answer

Immunodeficiency disorder

Question 2

An infant with a suspected metabolic disorder has abnormal newborn screening results. What is the most appropriate next step to confirm the diagnosis?

Accepted Answer

Conduct a comprehensive metabolic panel

Answer

Repeat the newborn screening

Answer

Start dietary modifications based on the most likely diagnosis

Answer

Obtain a detailed three-generation family history

Answer

Refer to genetics specialist without further testing

Question 3

Which genetic disorder is characterized by a deletion on chromosome 22 and includes features such as thymic hypoplasia and hypocalcemia?

Accepted Answer

DiGeorge syndrome

Answer

Down syndrome

Answer

Turner syndrome

Answer

Klinefelter syndrome

Answer

Williams syndrome

Question 4

A 6-month-old infant presents with failure to thrive and developmental delays. Serum laboratory results show elevated liver enzymes and bilirubin. What is the most likely diagnosis?

Accepted Answer

Biliary atresia

Answer

Hepatitis

Answer

Alpha-1 antitrypsin deficiency

Answer

Galactosemia

Answer

Wilson disease

Question 5

A 5-year-old girl presents with new-onset seizures, developmental delay, and hypopigmented macules on the skin. What is the most likely diagnosis?

Accepted Answer

Tuberous sclerosis

Answer

Neurofibromatosis type 1

Answer

Sturge-Weber syndrome

Answer

Von Hippel-Lindau disease

Answer

Rett syndrome

Question 6

Identify the best treatment to prevent complications in a newborn diagnosed with phenylketonuria (PKU).

Accepted Answer

Low-phenylalanine diet

Answer

High-protein diet

Answer

Gluten-free diet

Answer

Ketogenic diet

Answer

Enzyme replacement therapy

Question 7

What is the current term used to refer to Down syndrome?

Accepted Answer

Trisomy 21

Answer

Oligophrenia

Answer

Mental retardation

Answer

Intellectual disability

Answer

Mongolism

Question 8

What does the acronym LAHSAL represent in the context of congenital malformations?

Accepted Answer

Lip, Alveolus, Hard palate, Soft palate, and Alveolus-Lip classification

Answer

Congenital malformation of the Hard and Soft palate

Answer

Congenital malformation of the Lip

Answer

Congenital malformation of the Alveolus

Answer

None of the options

Question 9

Which of the following is a common feature of Down's syndrome?

Accepted Answer

Hypotonia

Answer

Early onset Alzheimer's disease

Answer

Congenital heart defects

Answer

Female infertility

Answer

Single palmar crease

Question 10

Which of the following is true regarding Turner's syndrome?

Accepted Answer

Monosomy of the X chromosome

Answer

Conductive hearing loss

Answer

Autosomal recessive inheritance

Answer

Increased carrying angle of the elbow (cubitus valgus)

Answer

Transmitted through maternal inheritance

Genetic and Metabolic Disorders — MCQs

Genetic and Metabolic Disorders — MCQs

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