USMLE Step 1 practice questions: a Step 1 qbank on the new 2026 format

B. Aldolase B

The timing is the whole question. Symptoms starting when fruit, juice or sucrose enters the diet, and not before, points to hereditary fructose intolerance, where aldolase B deficiency lets fructose-1-phosphate accumulate and trap intracellular phosphate. Depleted phosphate shuts down glycogenolysis and gluconeogenesis, giving the hypoglycemia and hepatomegaly described. Option A is classic galactosemia, which presents while the infant is still on breast milk or formula because the trigger is lactose, so the history rules it out. Option C, fructokinase deficiency, is essential fructosuria, and it is the deliberate near-miss: same sugar, but benign and asymptomatic because fructose-1-phosphate never accumulates. Option D is von Gierke disease, which causes fasting hypoglycemia from birth with no relationship to any specific sugar. Step 1 rarely asks you to name a deficiency in isolation; it gives you a dietary trigger and expects you to work backward.

A. Doxycycline for 14 days

This is primary syphilis, and in a non-pregnant adult with genuine anaphylactic penicillin allergy, doxycycline 100 mg twice daily for 14 days is the recommended alternative. Option C is the trap, and it is a good one, because desensitization genuinely is the answer in one specific circumstance: pregnancy, where no alternative regimen reliably treats the fetus. Absent pregnancy, subjecting a patient to desensitization when an effective oral alternative exists is unnecessary. Option B has some evidence but is not the preferred alternative regimen and carries cross-reactivity concern after anaphylaxis. Option D fails on resistance grounds: macrolide-resistant Treponema pallidum is widespread enough that azithromycin is not recommended. The pattern Step 1 tests here is that allergy questions almost always hinge on a modifier hidden in the stem, and pregnancy is the one that changes this answer.

C. Fluconazole

Fluconazole is a potent inhibitor of CYP2C9, the enzyme that clears the more pharmacologically active S-enantiomer of warfarin. Inhibit it and warfarin accumulates, the INR climbs, and bleeding follows, exactly as described. The other three options are all classic CYP inducers, and an inducer would push the INR down and raise clot risk, which is the opposite problem. Options A, B and D are grouped deliberately: if you know the induction list, you can eliminate three answers without knowing anything specific about fluconazole. That elimination strategy is worth practicing, because Step 1 pharmacology questions are frequently built so that the distractors share a mechanism and the answer is the odd one out. Chronic phenytoin is listed as an inducer, though phenytoin is worth a footnote because acutely it can also displace warfarin from protein binding, a nuance the exam usually avoids by specifying chronic use.

C. Squamous cell carcinoma

PTH-related peptide causing hypercalcemia with a suppressed native PTH is the signature paraneoplastic syndrome of squamous cell carcinoma of the lung, and the central location fits: squamous and small cell tumors arise centrally, adenocarcinoma peripherally. Option B is the answer most candidates reach for because small cell is the paraneoplastic tumor par excellence, but its syndromes are SIADH with hyponatremia, ectopic ACTH with Cushing syndrome, and Lambert-Eaton, not hypercalcemia. Option A is peripheral and is the tumor most associated with non-smokers and with hypertrophic osteoarthropathy. Option D is a diagnosis of exclusion with no characteristic paraneoplastic pattern. Two mnemonic anchors carry most lung questions on Step 1: squamous means central, cavitating, smoking and calcium, and small cell means central, neuroendocrine, and sodium or cortisol.

B. Inappropriate antidiuretic hormone secretion

Every number in the stem is doing work. Hyponatremia with concentrated urine at 600 mOsm/kg means ADH is acting when it should be fully suppressed, since a normal response to a low serum sodium is maximally dilute urine below about 100 mOsm/kg. Urine sodium above 40 with clinical euvolemia excludes a volume-depleted state, because a volume-depleted kidney avidly reabsorbs sodium and the urine sodium would be low. Option A, primary polydipsia, produces the opposite urine: dilute, because ADH is appropriately switched off. Option C requires hypovolemia, which the stem explicitly excludes, and cerebral salt wasting is distinguished from SIADH precisely by volume status. Option D is a hypervolemic cause with low urine sodium from renal hypoperfusion and secondary hyperaldosteronism. The exam wants you to classify hyponatremia by volume status first, then by urine studies, in that order.

B. Bruton tyrosine kinase mutation

Three findings lock this in: onset around 6 months, absent B cells, and low immunoglobulins across every class with intact T cells. That is X-linked agammaglobulinemia, where a BTK mutation halts B cell maturation at the pre-B stage. The 6-month timing is not incidental, it is the point at which transplacental maternal IgG has decayed, which is why these infants look well before then. Encapsulated organisms dominate because opsonizing antibody is the main defense against them. Option A is hyper-IgM syndrome, where B cells are present and IgM is normal or high with other classes low, since the failure is class switching rather than B cell development. Option C causes severe combined immunodeficiency, so T cells would not be normal. Option D is DiGeorge syndrome, a T cell problem presenting with hypocalcemic tetany, cardiac anomalies and viral or fungal infection, not an antibody pattern.

D. All of her children

Mitochondrial DNA is inherited exclusively from the mother, because the mitochondria in the zygote come from the ovum and paternal mitochondria are actively degraded after fertilization. Every child of an affected mother therefore inherits the mutant mitochondrial genome, and there is no sex difference in transmission. The important qualifier the exam expects you to understand is heteroplasmy: cells carry many mitochondrial genomes and inherit a variable mixture of mutant and normal, so all children are at risk but severity varies widely between siblings, which is why the correct phrasing is at risk rather than affected. Option A inverts the rule. Option B is the autosomal recessive fraction, and option C describes X-linked recessive transmission, which is the pattern candidates most often confuse with mitochondrial inheritance because both show maternal transmission. The distinguishing feature is that an X-linked recessive mother transmits to half her sons only, while a mitochondrial mother transmits to everyone.

D. Right hemisection of the cervical spinal cord

The combination that decides this is ipsilateral motor and dorsal column loss with completely intact pain and temperature. In Brown-Sequard syndrome the corticospinal tract and dorsal columns have already crossed above the lesion or cross in the medulla, so their deficits appear on the same side as the injury, while the spinothalamic tract crosses within a segment or two of entry, so its loss appears contralaterally. Here pain and temperature are described as intact bilaterally, which points to a very incomplete hemisection sparing the spinothalamic tract, and it is the facial sparing that places the lesion below the brainstem. Option A would give contralateral face, arm and leg weakness with contralateral sensory loss in all modalities. Option B, medial medullary syndrome, gives contralateral hemiparesis with contralateral dorsal column loss and ipsilateral tongue deviation. Option C, Wallenberg syndrome, is the opposite sensory picture entirely: it spares motor function and produces crossed pain and temperature loss.