FMGE 2026 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.

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.

Q: DNA matching used for identification and comparison among family members is based on analysis of which genetic marker?

Short tandem repeats (STRs). ***Short tandem repeats (STRs)*** - These are polymorphic DNA sequences consisting of **short nucleotide sequences** (typically 2-6 base pairs) repeated in tandem, making them highly variable and ideal for **individual identification**. - Because they are highly polymorphic, they provide high **discriminatory power** required for distinguishing between individuals and determining familial relationships via inheritance patterns. *Single nucleotide polymorphisms (SNPs)* - While useful for gene mapping and ancestry studies, SNPs are **bi-allelic markers** (only two possible variations), offering less discriminatory power per locus than STRs. - They are typically used for specific trait analysis or large-scale genome-wide studies rather than the standard **commercial forensic profiling** protocols used for identification. *Ribosomal RNA genes* - These genes are highly **conserved** across species and individuals, evolved to maintain essential protein synthesis functions. - Due to their high conservation, they lack the **variability** necessary for forensic identification or distinguishing between specific individuals. *Mitochondrial DNA* - Mitochondrial DNA is inherited exclusively through the **maternal lineage**, making it incapable of distinguishing between maternal relatives. - It has a much lower **power of discrimination** compared to nuclear DNA (like STRs) because it represents a single, non-recombining haplotype shared by all maternally related individuals.

Q: A child presents with easy bruising and bleeding. Physical examination reveals multiple ecchymoses and purpuric lesions over the body, as shown in the image. Hemarthrosis is absent. Deficiency of which vitamin best explains these findings?

Vitamin C. ***Vitamin C*** - Deficiency leads to **scurvy**, characterized by defective **collagen synthesis** due to the inability to hydroxylate proline and lysine residues. - Clinical features include **perifollicular hemorrhages**, swollen/bleeding gums, **petechiae**, and easy bruising, which aligns with the child's presentation. *Vitamin K* - Deficiency primarily causes coagulopathy, leading to deep tissue bleeding or **hemarthrosis** rather than exclusively cutaneous findings. - It relies on clotting factors II, VII, IX, and X, typically resulting in an elevated **prothrombin time (PT)** and PTT. *Vitamin D* - Deficiency leads to **rickets** in children or osteomalacia in adults due to impaired calcium and phosphate absorption, causing **bone deformities** and fractures. - It does not cause bleeding diathesis or spontaneous purpuric lesions in the absence of severe liver disease or complications. *Vitamin A* - Deficiency typically presents with **night blindness**, dry eyes (xerophthalmia), and **keratomalacia** due to impaired ocular epithelial maintenance. - Dermatological manifestations involve **follicular hyperkeratosis** (phrynoderma), not purpura or easy bruising.

Q: Eruptive xanthomas with a prominent chylomicron band on lipid electrophoresis are most commonly seen due to:

Lipoprotein lipase (LPL) deficiency. ***Lipoprotein lipase (LPL) deficiency*** - This condition, classified as **Familial Chylomicronemia Syndrome (Type I Hyperlipoproteinemia)**, is characterized by the accumulation of **chylomicrons** in the plasma due to defective hydrolysis of triglycerides. - Clinically, it presents with **eruptive xanthomas**, **pancreatitis**, and **hepatosplenomegaly**, often appearing in childhood with extremely high **serum triglyceride levels**. *LDL receptor defect* - This pathology causes **Familial Hypercholesterolemia (Type IIa Hyperlipoproteinemia)**, characterized by elevated **LDL cholesterol**. - It typically results in **tendon xanthomas** and **xanthelasma**, not eruptive xanthomas, and presents primarily with increased risk of premature **coronary artery disease**. *Apo B-100 deficiency* - This leads to **hypobetalipoproteinemia**, where there is an inability to assemble VLDL, resulting in very low levels of **LDL** and **VLDL**. - It does not cause hypertriglyceridemia or eruptive xanthomas; instead, it is associated with **fat malabsorption** and **vitamin E deficiency**. *Apo E deficiency* - This is associated with **Familial Dysbetalipoproteinemia (Type III Hyperlipoproteinemia)**, which results in the accumulation of **remnant particles** (IDL and chylomicron remnants). - Characteristic findings include **tuberoeruptive** and **palmar xanthomas**, rather than the acute eruptive xanthomas seen in classic Chylomicronemia syndrome.

Q: A patient presents with ataxia, ichthyosis, retinitis pigmentosa, and cardiac conduction defects. Laboratory evaluation reveals increased phytanic acid levels. What is the most likely diagnosis?

Refsum disease. ***Refsum disease*** - Caused by a deficiency of **peroxisomal phytanoyl-CoA hydroxylase**, leading to the accumulation of **phytanic acid**, which is toxic to the nervous system. - The classic clinical tetrad includes **ataxia**, **ichthyosis** (scaling of the skin), **retinitis pigmentosa** (causing night blindness), and **cardiac conduction defects** (arrhythmias). *Zellweger disease* - This is a severe peroxisome biogenesis disorder characterized by the **absence of functional peroxisomes** entirely rather than a specific enzyme defect. - Patients typically present with **craniofacial dysmorphism**, hypotonia, and seizures in early infancy with a much poorer prognosis. *Adrenoleukodystrophy* - Results from a mutation in the **ABCD1 gene**, leading to impaired beta-oxidation and the accumulation of **very-long-chain fatty acids (VLCFAs)**. - Clinical features primarily involve **adrenal insufficiency** (Addison disease) and progressive **neurological deterioration** rather than ichthyosis or elevated phytanic acid. *Metachromatic leukodystrophy* - Caused by a deficiency of **arylsulfatase A**, leading to the accumulation of **sulfatides** in the central and peripheral nervous system. - It is characterized by progressive **demyelination** leading to ataxia, dementia, and seizures, without the feature of elevated phytanic acid levels.

Q: Female in labor shows abrupt fetal bradycardia after spontaneous rupture of membrane. Cervix is 6cm dilated. 5/5 of the head is palpable. Diagnosis?

Cord prolapse. ***Cord prolapse*** - Sudden fetal bradycardia following rupture of membranes with a high, unengaged fetal head (5/5 palpable) is the classic presentation of **umbilical cord prolapse**, which causes acute cord compression and fetal hypoxia. - This is an **obstetric emergency** requiring immediate delivery, typically via **emergency cesarean section**, to alleviate the cord compression. *Abruption* - While **placental abruption** causes fetal compromise, the classic presentation includes **vaginal bleeding** and a firm, tender uterus, rather than the isolated fetal bradycardia seen here. - Abruption typically occurs over time or following trauma/hypertension, whereas the bradycardia here is temporally linked specifically to the rupture of membranes. *Uterine prolapse* - **Uterine prolapse** is unlikely during labor as the uterus is held in place by the cervix and supporting ligaments, and it does not present with acute fetal bradycardia. - It would present as a mass protruding through the introitus, which is not described in this acute clinical scenario of fetal distress. *Vasa previa* - **Vasa previa** is a condition where fetal vessels traverse the membranes near the cervix, which rupture upon membrane tear, leading to **painless vaginal bleeding** and rapid fetal exsanguination. - While it causes fetal bradycardia, it is classically associated with vaginal bleeding immediately following rupture of membranes, not noted in this case describing a high unengaged head.

Q: A child presents with hepatosplenomegaly, anemia, and bone pain. Histopathological examination reveals macrophages with a “crumpled tissue paper” appearance due to cerebroside accumulation. Deficiency of which enzyme is responsible for this condition?

β-Glucocerebrosidase. ***β-Glucocerebrosidase*** - This condition is **Gaucher disease**, which is caused by a deficiency of the **β-glucocerebrosidase** enzyme, leading to the accumulation of **glucocerebroside** in lysosomes. - The characteristic **Gaucher cells** demonstrate an accumulation of substrate giving them a pathognomonic **crumpled tissue paper** appearance in the spleen, liver, and bone marrow. *Hexosaminidase A* - Deficiency of this enzyme leads to **Tay-Sachs disease**, characterized by **progressive neurodegeneration** and a **cherry-red macula**. - Cells in Tay-Sachs exhibit **onion-skin** lysosomal inclusions, distinct from the Gaucher cell inclusions. *Sphingomyelinase* - Deficiency of sphingomyelinase leads to **Niemann-Pick disease** (Type A and B). - Patients with Niemann-Pick typically present with **hepatosplenomegaly** and **cherry-red macula**, but the cells demonstrate **foam cells** (lipid-laden macrophages) rather than crumpled tissue paper. *Arylsulfatase A* - Deficiency of arylsulfatase A results in **metachromatic leukodystrophy**, a demyelinating disease of the central and peripheral nervous system. - Clinical presentation involves **ataxia**, **dementia**, and **seizures** rather than the viseo-visceral manifestations like hepatosplenomegaly found in this patient.

Q: A child presents with hepatosplenomegaly. Histological examination shows foam cells due to lipid accumulation. What is the most likely diagnosis?

Niemann –Pick disease. ***Niemann–Pick disease*** - Niemann–Pick disease, specifically type A and B, is caused by a **deficiency of sphingomyelinase**, leading to the accumulation of **sphingomyelin** within lysosomes. - The hallmark histological finding is the presence of **foam cells** (lipid-laden macrophages) in organs like the spleen, liver, and bone marrow, which correlates with the clinical finding of **hepatosplenomegaly**. *Gaucher disease* - Gaucher disease involves the accumulation of **glucocerebroside** due to a deficiency of the enzyme **glucocerebrosidase**. - Histologically, this presents as **Gaucher cells**, which are described as having the appearance of **wrinkled tissue paper** or crumpled silk, rather than foam cells. *Tay–Sachs disease* - Tay–Sachs disease is characterized by a deficiency in **hexosaminidase A**, leading to the accumulation of **GM2 gangliosides**. - It primarily affects the **central nervous system**, causing a **cherry-red spot** in the macula and neurodegeneration, but does **not** cause hepatosplenomegaly. *Fabry disease* - Fabry disease is an X-linked recessive disorder caused by a deficiency of **alpha-galactosidase A**, leading to the accumulation of **globotriaosylceramide**. - Clinical features typically include peripheral neuropathy, **angiokeratomas**, and hypohidrosis, generally without hepatosplenomegaly.

Q: A child is evaluated for cardiomegaly and features of heart failure. Laboratory investigations show maltase deficiency. What is the most likely diagnosis?

Pompe disease. ***Pompe disease*** - Also known as **Glycogen Storage Disease Type II**, this condition is caused by a deficiency of the lysosomal enzyme **acid alpha-glucosidase (acid maltase)**, which leads to glycogen accumulation in tissues. - It is classically characterized by severe **cardiomegaly** and **hypertrophic cardiomyopathy** in infancy, often leading to early heart failure, alongside **hypotonia** and macroglossia. *McArdle disease* - This is **Glycogen Storage Disease Type V**, caused by a deficiency of **muscle phosphorylase**, which typically presents in adolescence or adulthood. - Patients characteristically suffer from **exercise intolerance**, **muscle cramps**, and **myoglobinuria** rather than cardiac involvement. *Von Gierke disease* - This is **Glycogen Storage Disease Type I**, resulting from a deficiency of **glucose-6-phosphatase**. - Clinical features are dominated by **severe fasting hypoglycemia**, **hepatomegaly**, and **lactic acidosis**, not primary cardiomyopathy. *Cori disease* - This is **Glycogen Storage Disease Type III**, caused by a deficiency of the **debranching enzyme**. - It presents primarily with **hepatomegaly**, growth retardation, and variable **myopathy**, but it generally lacks the severe hypertrophic cardiomyopathy seen in Pompe disease.

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

DNA matching used for identification and comparison among family members is based on analysis of which genetic marker?

Accepted Answer

Short tandem repeats (STRs)

Answer

Single nucleotide polymorphisms (SNPs)

Answer

Ribosomal RNA genes

Answer

Mitochondrial DNA

Question 4

A child presents with easy bruising and bleeding. Physical examination reveals multiple ecchymoses and purpuric lesions over the body, as shown in the image. Hemarthrosis is absent. Deficiency of which vitamin best explains these findings?

Accepted Answer

Vitamin C

Answer

Vitamin K

Answer

Vitamin D

Answer

Vitamin A

Question 5

Eruptive xanthomas with a prominent chylomicron band on lipid electrophoresis are most commonly seen due to:

Accepted Answer

Lipoprotein lipase (LPL) deficiency

Answer

LDL receptor defect

Answer

Apo B-100 deficiency

Answer

Apo E deficiency

Question 6

A patient presents with ataxia, ichthyosis, retinitis pigmentosa, and cardiac conduction defects. Laboratory evaluation reveals increased phytanic acid levels. What is the most likely diagnosis?

Accepted Answer

Refsum disease

Answer

Zellweger disease

Answer

Adrenoleukodystrophy

Answer

Metachromatic leukodystrophy

Question 7

Female in labor shows abrupt fetal bradycardia after spontaneous rupture of membrane. Cervix is 6cm dilated. 5/5 of the head is palpable. Diagnosis?

Accepted Answer

Cord prolapse

Answer

Abruption

Answer

Uterine prolapse

Answer

Vasa previa

Question 8

A child presents with hepatosplenomegaly, anemia, and bone pain. Histopathological examination reveals macrophages with a “crumpled tissue paper” appearance due to cerebroside accumulation. Deficiency of which enzyme is responsible for this condition?

Accepted Answer

β-Glucocerebrosidase

Answer

Hexosaminidase A

Answer

Sphingomyelinase

Answer

Arylsulfatase A

Question 9

A child presents with hepatosplenomegaly. Histological examination shows foam cells due to lipid accumulation. What is the most likely diagnosis?

Accepted Answer

Niemann –Pick disease

Answer

Gaucher disease

Answer

Tay–Sachs disease

Answer

Fabry disease

Question 10

A child is evaluated for cardiomegaly and features of heart failure. Laboratory investigations show maltase deficiency. What is the most likely diagnosis?

Accepted Answer

Pompe disease

Answer

McArdle disease

Answer

Von Gierke disease

Answer

Cori disease

FMGE 2026

Biochemistry

Forensic Medicine

Internal Medicine

Obstetrics and Gynecology

Pathology

Pediatrics