Phenylketonuria and Alkaptonuria — MCQs
Ochronosis is due to the accumulation of?
Phenylketonuria is due to a deficiency of:
In phenylketonuria, which substance should be restricted in the diet?
In alkaptonuria, deficiency is:
A patient presents with ochronosis. Which of the following substance accumulates in this condition?
A patient reports a change in colour of urine on air exposure. All are true about the condition shown below except:
A 4-year-old boy of a first-degree consanguineous couple was noted by the parents to have darkening of the urine to an almost black color when it was left standing. He has a normal sibling, and there are no other medical problems. Growth and development to date are normal. Which of the following is most likely to be elevated in this patient?
A patient complains of knee pain. Routine investigations are unremarkable and still, the patient is unsatisfied. Urine turns black on standing, what is the enzyme involved?
VMA is excreted in urine in which condition -
Coenzyme for phenylalanine hydroxylase is?
Phenylketonuria and Alkaptonuria Indian Medical PG Practice Questions and MCQs
Question 1: Ochronosis is due to the accumulation of?
- A. Homogentisic acid (Correct Answer)
- B. Alkapton
- C. Xanthurenate
- D. Glyoxylate
Explanation: ***Homogentisic acid (Correct)*** - **Ochronosis** is a rare genetic disorder characterized by the accumulation of **homogentisic acid** in connective tissues. - This accumulation results from a deficiency of the enzyme **homogentisate 1,2-dioxygenase**, which is crucial in the catabolism of tyrosine and phenylalanine. - Clinically presents with dark pigmentation of cartilage, sclera, and other connective tissues. *Alkapton (Incorrect)* - While **alkaptonuria** is the disease caused by homogentisic acid accumulation, **alkapton** itself is not the substance that accumulates in tissues in ochronosis. - **Alkapton** refers to the dark-colored urine observed in patients with alkaptonuria, which is due to the oxidation of homogentisic acid in the urine. *Xanthurenate (Incorrect)* - **Xanthurenate** is an intermediate in the metabolism of tryptophan, and its accumulation is associated with certain vitamin B6 deficiencies. - It is not involved in the pathogenesis of ochronosis or alkaptonuria. *Glyoxylate (Incorrect)* - **Glyoxylate** is a metabolic intermediate involved in various pathways, including carbohydrate and amino acid metabolism. - Accumulation of glyoxylate is associated with **primary hyperoxaluria type 1**, but not with ochronosis.
Question 2: Phenylketonuria is due to a deficiency of:
- A. Phenylalanine hydroxylase (PAH) (Correct Answer)
- B. Galactokinase
- C. Tyrosinase
- D. Phenylalanine
Explanation: ***Phenylalanine hydroxylase (PAH)*** - **Phenylketonuria (PKU)** is an autosomal recessive disorder caused by a deficiency of the enzyme **phenylalanine hydroxylase (PAH)**. - This enzyme is crucial for converting the amino acid **phenylalanine** to **tyrosine**. *Phenylalanine* - Phenylalanine is the **substrate** that accumulates in PKU due to the enzyme deficiency, not the deficiency itself. - High levels of phenylalanine are **toxic** to the brain and lead to the clinical manifestations of PKU. *Galactokinase* - Deficiency of **galactokinase** is associated with **galactosemia type II**, a disorder of galactose metabolism. - This condition is characterized by **cataracts** and typically does not involve the neurologic symptoms seen in PKU. *Tyrosinase* - **Tyrosinase** deficiency is the primary cause of **oculocutaneous albinism type 1**, affecting melanin synthesis. - It results in hypopigmentation of the skin, hair, and eyes, which is unrelated to PKU.
Question 3: In phenylketonuria, which substance should be restricted in the diet?
- A. Tyrosine
- B. Phenylalanine (Correct Answer)
- C. Maize
- D. None of the options
Explanation: ***Phenylalanine*** - **Phenylketonuria (PKU)** is a genetic disorder where the body cannot effectively metabolize **phenylalanine** due to a deficiency in the enzyme **phenylalanine hydroxylase**. - Restricting dietary phenylalanine is crucial to prevent the accumulation of toxic byproducts that can lead to severe neurological damage and developmental delays. *Tyrosine* - Tyrosine is normally synthesized from phenylalanine. In PKU, this conversion is impaired. - While phenylalanine must be restricted, tyrosine supplementation is often necessary for individuals with PKU, as it becomes a conditionally essential amino acid. *Maize* - Maize (corn) is a carbohydrate-rich food and does not contain high levels of phenylalanine that would necessitate its restriction in PKU. - Dietary management in PKU focuses on regulating protein intake, as phenylalanine is an amino acid found in proteins. *None of the options* - This option is incorrect because phenylalanine must be strictly restricted in the diet of individuals with phenylketonuria to manage the condition effectively. - Without dietary restriction, the accumulation of phenylalanine can lead to severe and irreversible neurological damage.
Question 4: In alkaptonuria, deficiency is:
- A. Phosphofructokinase
- B. HMG CoA reductase
- C. Homogentisate oxidase (Correct Answer)
- D. Xanthine oxidase
Explanation: ***Homogentisate oxidase*** - **Alkaptonuria** is an autosomal recessive disorder caused by a deficiency of the enzyme **homogentisate 1,2-dioxygenase** (also known as homogentisate oxidase). - This enzyme is crucial in the **catabolic pathway of tyrosine**, specifically breaking down **homogentisic acid**. *Phosphofructokinase* - Deficiency of **phosphofructokinase** (PFK) causes **Tarui's disease** (Glycogen Storage Disease Type VII), affecting **glycolysis**. - Symptoms include exercise intolerance, muscle pain, and hemolysis, which are unrelated to alkaptonuria. *HMG CoA reductase* - **HMG-CoA reductase** is the rate-limiting enzyme in **cholesterol biosynthesis**, and its inhibitors (statins) are used to lower cholesterol levels. - Its deficiency is not associated with alkaptonuria. *Xanthine oxidase* - **Xanthine oxidase** is involved in the catabolism of **purines**, converting hypoxanthine to xanthine and then xanthine to uric acid. - Its deficiency causes **xanthinuria**, leading to kidney stones, and it is not associated with alkaptonuria.
Question 5: A patient presents with ochronosis. Which of the following substance accumulates in this condition?
- A. Homogentisic acid (Correct Answer)
- B. Phenylalanine
- C. Tyrosine
- D. Tryptophan
Explanation: ***Homogentisic acid*** - Ochronosis (alkaptonuria) is caused by the accumulation of **homogentisic acid** in connective tissues, leading to a dark blue-black discoloration of cartilage, skin, and organs. - This accumulation results from a deficiency of **homogentisate 1,2-dioxygenase**, an enzyme involved in the metabolism of **tyrosine**. - The accumulated homogentisic acid polymerizes and deposits in tissues, causing the characteristic pigmentation. *Phenylalanine* - Accumulation of **phenylalanine** occurs in **phenylketonuria (PKU)**, not ochronosis. - PKU is caused by deficiency of phenylalanine hydroxylase and presents with intellectual disability, musty odor, and fair complexion if untreated. *Tyrosine* - While ochronosis involves a defect in **tyrosine metabolism**, tyrosine itself does not accumulate in this condition. - Tyrosine accumulation occurs in **tyrosinemia**, which presents with different clinical features including hepatic dysfunction and renal tubular defects. *Tryptophan* - Defects in **tryptophan metabolism** are associated with conditions like **Hartnup disease**, which presents with pellagra-like symptoms, not ochronosis. - Tryptophan is a precursor for **serotonin** and **niacin (vitamin B3)**.
Question 6: A patient reports a change in colour of urine on air exposure. All are true about the condition shown below except:
- A. Blackening of urine is accelerated on exposure to sunlight
- B. Alkaptone bodies are deposited in intervertebral disc
- C. Urine Benedict's test is negative (Correct Answer)
- D. The condition is caused by deficiency of tyrosine aminotransferase
Explanation: ***Urine Benedict's test is negative*** - This is FALSE - Benedict's test is actually **POSITIVE** in alkaptonuria because **homogentisic acid** is a reducing agent. - Homogentisic acid readily **reduces Benedict's reagent**, giving a positive test result in alkaptonuria patients. - This is the **correct answer** to this EXCEPT question. *Blackening of urine is accelerated on exposure to sunlight* - This is TRUE - **UV light** and sunlight accelerate the **oxidation of homogentisic acid** in urine. - The characteristic **dark discoloration** occurs more rapidly when exposed to light and air. *Alkaptone bodies are deposited in intervertebral disc* - This is TRUE - **Homogentisic acid (alkaptone bodies)** polymerizes to form **ochronotic pigment** deposits. - These deposits accumulate in **cartilage** including intervertebral discs, causing degenerative changes and spondylosis. *The condition is caused by deficiency of tyrosine aminotransferase* - This is FALSE - Alkaptonuria is caused by deficiency of **homogentisate 1,2-dioxygenase**, not tyrosine aminotransferase. - **Tyrosine aminotransferase** deficiency causes Tyrosinemia Type II (Richner-Hanhart syndrome), a different condition. - However, Option C (Benedict's test) is the **more clearly incorrect** statement and the intended answer.
Question 7: A 4-year-old boy of a first-degree consanguineous couple was noted by the parents to have darkening of the urine to an almost black color when it was left standing. He has a normal sibling, and there are no other medical problems. Growth and development to date are normal. Which of the following is most likely to be elevated in this patient?
- A. Methylmalonate
- B. Homogentisate (Correct Answer)
- C. Phenylpyruvate
- D. α-Ketoisovalerate
Explanation: ***Homogentisate*** - The darkening of urine upon standing, especially in a child from a consanguineous marriage, is a classic presentation of **alkaptonuria**. - **Alkaptonuria** is an autosomal recessive disorder caused by a deficiency of **homogentisate 1,2-dioxygenase**, leading to an accumulation of homogentisate. *Methylmalonate* - Elevated **methylmalonate** is characteristic of **methylmalonic aciduria**, a disorder of amino acid metabolism. - This condition typically presents with metabolic acidosis, developmental delay, and feeding difficulties, which are not described here. *Phenylpyruvate* - Elevated **phenylpyruvate** is a key finding in **phenylketonuria (PKU)**, an autosomal recessive disorder of phenylalanine metabolism. - PKU usually presents with severe intellectual disability if untreated, along with a musty odor, none of which are consistent with the patient's symptoms. *α-Ketoisovalerate* - Elevated **α-ketoisovalerate** is a diagnostic marker for **maple syrup urine disease (MSUD)**. - MSUD typically presents in infancy with poor feeding, lethargy, maple syrup odor in urine, and neurological deterioration, which differ from the presented case.
Question 8: A patient complains of knee pain. Routine investigations are unremarkable and still, the patient is unsatisfied. Urine turns black on standing, what is the enzyme involved?
- A. Methylmalonyl-CoA mutase
- B. Homogentisate oxidase (Correct Answer)
- C. Xanthine oxidase
- D. Tyrosine hydroxylase
Explanation: ***Homogentisate oxidase*** - **Homogentisate oxidase** deficiency leads to **alkaptonuria**, where homogentisic acid accumulates and is excreted in urine, turning it black upon standing or exposure to air. The knee pain could be due to **ochronosis**, the deposition of oxidized homogentisic acid in cartilage and connective tissues. - The unremarkable routine investigations with persistent knee pain suggest a less common metabolic disorder, which is consistent with **alkaptonuria**'s chronic and insidious presentation. *Methylmalonyl-CoA mutase* - A deficiency in **methylmalonyl-CoA mutase** causes **methylmalonic acidemia**, a metabolic disorder typically presenting in infancy with neurological symptoms, feeding difficulties, and developmental delay. - It does not cause urine to turn black on standing or lead to specific joint pain like that seen in ochronosis. *Xanthine oxidase* - **Xanthine oxidase** is involved in purine metabolism, and its inhibition (e.g., by allopurinol) is used to treat **gout**. - While gout can cause knee pain, it is characterized by elevated uric acid and typically responds to conventional treatments and the urine does not turn black. *Tyrosine hydroxylase* - **Tyrosine hydroxylase** is the rate-limiting enzyme in catecholamine synthesis, converting tyrosine to L-DOPA. - Defects in this enzyme are rare and result in neurological disorders, such as **DOPA-responsive dystonia**, and do not cause urine to blacken or lead to direct joint damage.
Question 9: VMA is excreted in urine in which condition -
- A. Alkaptonuria
- B. Phenylketonuria
- C. Diabetic ketoacidosis
- D. Pheochromocytoma (Correct Answer)
Explanation: ***Pheochromocytoma*** - Pheochromocytoma is characterized by excessive secretion of catecholamines, leading to increased levels of **vanillylmandelic acid (VMA)** in the urine. - It is often associated with symptoms like **hypertension**, palpitations, and sweating due to catecholamine release. *Alkaptonuria* - Caused by a deficiency in **homogentisate oxidase**, leading to the accumulation of **homogentisic acid**, not VMA. - Clinically presents with **dark urine** and can lead to **ochronosis**, but does not involve catecholamines. *Phenylketonuria* - A metabolic disorder resulting from a deficiency in **phenylalanine hydroxylase**, leading to elevated levels of **phenylalanine** rather than VMA. - Symptoms include intellectual disability and musty odor, unrelated to catecholamine metabolism. *Diabetic ketoacidosis* - This is a condition caused by severe **insulin deficiency**, resulting in elevated ketone bodies and glucose levels, but does not cause increased VMA excretion. - Symptoms include **fruity breath**, dehydration, and metabolic acidosis, focusing on ketone production rather than catecholamine metabolism.
Question 10: Coenzyme for phenylalanine hydroxylase is?
- A. Tetrahydrofolate
- B. Pyridoxal phosphate
- C. S-adenosyl methionine
- D. Tetrahydrobiopterin (Correct Answer)
Explanation: ***Tetrahydrobiopterin*** - **Tetrahydrobiopterin (BH4)** is an essential coenzyme for aromatic amino acid hydroxylases, including **phenylalanine hydroxylase (PAH)**. - PAH converts **phenylalanine** to **tyrosine**, and deficiencies in BH4 or PAH itself lead to *phenylketonuria (PKU)*. *Tetrahydrofolate* - **Tetrahydrofolate (THF)** is a coenzyme derived from **folic acid** and is primarily involved in **one-carbon metabolism**, including **purine** and **pyrimidine synthesis**, and various amino acid interconversions. - It does not directly act as a coenzyme for phenylalanine hydroxylase. *Pyridoxal phosphate* - **Pyridoxal phosphate (PLP)**, a derivative of **vitamin B6**, is a crucial coenzyme for many enzymes involved in **amino acid metabolism**, particularly in **transamination**, **decarboxylation**, and side-chain cleavage reactions. - It is not the coenzyme for phenylalanine hydroxylase. *S-adenosyl methionine* - **S-adenosyl methionine (SAM)** is a major **methyl donor** in various biochemical reactions, important for the synthesis of **neurotransmitters**, **hormones**, and **phospholipids**. - While essential for many metabolic pathways, it is not involved as a coenzyme for phenylalanine hydroxylase.
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