**Core Concept:** Hirschsprung disease is a congenital disorder characterized by the absence of ganglion cells in the submucosa of the rectum and the colon, leading to impaired peristalsis and motility.

**Why the Correct Answer is Right:** Hirschsprung disease is confirmed by performing a biopsy of the affected segment and observing the absence of ganglion cells in the submucosa. This test provides definitive evidence for the diagnosis.

**Why Each Wrong Option is Incorrect:**

A. Colonoscopy: While colonoscopy may reveal dilated colon, it does not specifically confirm the absence of ganglion cells, which is crucial for the diagnosis of Hirschsprung disease.
B. Barium enema: A barium enema may show megacolon but does not provide the histopathological evidence of ganglion cell absence, unlike biopsy.
C. Biopsy: Performing a biopsy is essential to confirm the diagnosis, but the focus here is on observing the absence of ganglion cells in the submucosa.
D. Clinical presentation: Hirschsprung disease's clinical features are non-specific and can be seen in other conditions as well, making them insufficient for definitive diagnosis.

**Clinical Pearl:** A crucial clinical pearl is that Hirschsprung disease typically presents in infants with constipation, abdominal distension, and failure to pass meconium. However, the diagnosis should not solely rely on clinical features as other conditions can mimic these symptoms.

**Correct Answer:** D. Biopsy: The definitive diagnosis of Hirschsprung disease requires obtaining a biopsy from the affected segment, examining the submucosa for the absence of ganglion cells, which confirms the diagnosis.