FMGE 2026 - Biochemistry PYQs Practice Questions

Q: A patient presents with photosensitivity, purpura, and blistering skin lesions on sun-exposed areas. Biochemical evaluation shows a defect in the conversion of uroporphyrinogen III to coproporphyrinogen III in the heme synthesis pathway. Which enzyme is deficient?

Uroporphyrinogen decarboxylase. ***Uroporphyrinogen decarboxylase*** - A deficiency in this enzyme leads to **Porphyria Cutanea Tarda (PCT)**, the most common form of porphyria. - It results in the accumulation of uroporphyrinogen, causing characteristic **photosensitivity**, **vesiculobullous skin lesions**, and hyperpigmentation in **sun-exposed areas**. *Coproporphyrinogen oxidase* - A deficiency here causes **Hereditary Coproporphyria**, which typically presents with a combination of neurovisceral symptoms and cutaneous photosensitivity. - This enzyme catalyzes the downstream conversion of **coproporphyrinogen III** to protoporphyrinogen IX, not the step involving uroporphyrinogen. *Ferrochelatase* - This enzyme catalyzes the final step in heme synthesis: the incorporation of **ferrous iron** into protoporphyrin IX. - Deficiency results in **Erythropoietic Protoporphyria**, which presents with acute **photosensitivity** (burning/stinging) rather than the blistering lesions seen in PCT. *Porphobilinogen deaminase* - Deficiency of this enzyme causes **Acute Intermittent Porphyria (AIP)**, characterized by episodic abdominal pain, neuropsychiatric symptoms, and tachycardia. - Crucially, AIP **does not** typically present with the photosensitivity or blistering skin lesions described in this case. [Practice more Biochemistry PYQs on OnCourse]

Q: A child presents with self-mutilating behavior, developmental delay, and hyperuricemia. Deficiency of which enzyme is responsible for this condition?

Hypoxanthine -guanine phosphoribosyltransferase (HGPRTase). ***Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase)*** - Deficiency leads to **Lesch-Nyhan syndrome**, characterized by the classic clinical triad of extreme **hyperuricemia**, **developmental delay**, and hallmark **self-mutilating behavior** (e.g., lip and finger biting). - This enzyme is crucial for the **purine salvage pathway**; its absence results in the shunting of accumulated substrates toward **de novo purine synthesis**, markedly increasing uric acid production. *Adenosine deaminase* - Deficiency is the most common cause of **severe combined immunodeficiency (SCID)** and typically presents with recurrent fungal, viral, and bacterial infections. - It is not associated with movement disorders, intellectual disability, or the specific self-mutilation seen in this case. *Xanthine oxidase* - This enzyme catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid; its inhibition (e.g., by **allopurinol**) is a treatment for hyperuricemia. - Deficiency leads to **xanthinuria** and potentially **xanthine stones**, but not the neurobehavioral abnormalities observed here. *Glucose-6-phosphatase* - This enzyme is deficient in **Von Gierke disease (Glycogen Storage Disease Type I)**, which presents with severe **fasting hypoglycemia** and hepatomegaly. - Patients may develop gout due to secondary hyperuricemia, but they do not exhibit the characteristic self-mutilating impulses seen in HGPRT deficiency. [Practice more Biochemistry PYQs on OnCourse]

Q: A neonate presents with seizures, low citrulline levels, hyperammonemia, normal orotic acid levels, and high glutamine. What is the most likely diagnosis?

Type I hyperammonemia. ***Type I hyperammonemia*** - Caused by a deficiency of **carbamoyl phosphate synthetase I (CPS I)**, which is the rate-limiting step of the urea cycle. - This block prevents the formation of carbamoyl phosphate, leading to **low orotic acid** and **low citrulline** levels, distinguishing it from OTC deficiency. *Type II hyperammonemia* - Caused by a deficiency of **ornithine transcarbamylase (OTC)**, the most common urea cycle disorder. - This condition is characterized by **elevated orotic acid** in blood and urine due to the accumulation of carbamoyl phosphate being shunted into the pyrimidine synthesis pathway. *Citrullinemia* - Results from a deficiency of **argininosuccinate synthetase**, preventing the condensation of citrulline and aspartate. - It classically presents with **markedly elevated citrulline levels** in the plasma, which contradicts the low citrulline finding in this patient. *Argininosuccinic aciduria* - Caused by a deficiency of **argininosuccinate lyase**, leading to the accumulation of argininosuccinate. - Patients typically show **elevated levels of argininosuccinate** and citrulline, rather than the low citrulline profile observed here. [Practice more Biochemistry PYQs on OnCourse]

Question 1

A patient presents with photosensitivity, purpura, and blistering skin lesions on sun-exposed areas. Biochemical evaluation shows a defect in the conversion of uroporphyrinogen III to coproporphyrinogen III in the heme synthesis pathway. Which enzyme is deficient?

Accepted Answer

Uroporphyrinogen decarboxylase

Answer

Coproporphyrinogen oxidase

Answer

Ferrochelatase

Answer

Porphobilinogen deaminase

Question 2

A child presents with self-mutilating behavior, developmental delay, and hyperuricemia. Deficiency of which enzyme is responsible for this condition?

Accepted Answer

Hypoxanthine -guanine phosphoribosyltransferase (HGPRTase)

Answer

Adenosine deaminase

Answer

Xanthine oxidase

Answer

Glucose-6-phosphatase

Question 3

A neonate presents with seizures, low citrulline levels, hyperammonemia, normal orotic acid levels, and high glutamine. What is the most likely diagnosis?

Accepted Answer

Type I hyperammonemia

Answer

Type II hyperammonemia

Answer

Citrullinemia

Answer

Argininosuccinic aciduria

FMGE 2026 — Biochemistry