What is the differential diagnosis of a 13-year-old boy with an aganglionic colon?

Differential Diagnosis of Aganglionic Colon in a 13-Year-Old Boy

The primary differential diagnosis for aganglionic colon in a 13-year-old is total colonic aganglionosis (TCA), an extensive variant of Hirschsprung's disease, though presentation at this age is exceptionally rare and requires exclusion of other neuronal intestinal dysplasias and chronic pseudo-obstruction syndromes. 1

Primary Consideration: Total Colonic Aganglionosis (TCA)

TCA represents 14% of all Hirschsprung's disease cases but almost universally presents in infancy, making diagnosis in a 13-year-old highly unusual and often delayed. 2

• Patients with TCA typically present within the first weeks to months of life, with nearly all cases diagnosed by the end of the first year 1
• Late presentation in older children or adolescents occurs when the diagnosis is missed, leading to repeated laparotomies for subacute intestinal obstruction without symptom relief 1
• Without high clinical suspicion, these cases undergo inadvertent bowel resections and multiple unsuccessful surgical interventions 1

Diagnostic Approach for TCA

• Rectal suction or full-thickness biopsy is mandatory to confirm absence of ganglion cells in the distal bowel 2, 3
• Multiple intestinal biopsies at laparotomy are required to document the proximal extent of aganglionosis 2
• Laparoscopic-assisted colonic mapping provides a minimally invasive method to obtain full-thickness biopsies from multiple colonic segments (sigmoid, transverse, ascending colon) without additional laparotomy 4
• Acetylcholinesterase staining on rectal biopsy specimens enhances diagnostic accuracy, showing increased cholinergic innervation in affected bowel 3

Secondary Differential: Intestinal Neuronal Dysplasia (IND)

IND can coexist with Hirschsprung's disease or present independently, characterized by hyperganglionosis rather than aganglionosis. 3

• Type B IND may extend proximally beyond the aganglionic segment in patients with concurrent Hirschsprung's disease 4
• Laparoscopic colonic mapping revealed coexistent type B IND extending to the descending colon in one case series 4
• Histologically, IND shows increased ganglion cells per ganglion (hyperganglionosis), distinguishing it from true aganglionosis 3

Tertiary Differential: Hypoganglionosis

Hypoganglionosis represents a spectrum disorder with reduced but present ganglion cells, requiring full-thickness biopsies for diagnosis. 4

• Rectal suction biopsies may be suspicious but insufficient for definitive diagnosis 4
• Full-thickness biopsies from multiple colonic segments documented hypoganglionosis extending to the ascending colon in pediatric case series 4
• This condition shares clinical presentation with Hirschsprung's disease but has distinct histopathologic features 3

Additional Considerations: Chronic Intestinal Pseudo-Obstruction (CIIP)

CIIP presents with chronic constipation and obstruction symptoms but demonstrates myopathic rather than neuropathic pathology. 3

• CIIP shares clinical features with Hirschsprung's disease but shows normal ganglion cell distribution 3
• Increased VIPergic immunostaining is present in CIIP, though this pattern is not diagnostically selective 3
• Myopathic changes in the intestinal smooth muscle distinguish CIIP from neuronal disorders 3

Inflammatory Bowel Disease Considerations

While the question specifies aganglionic colon, it is critical to note:

• In children under 10 years, ulcerative colitis can present with atypical histology including relative rectal sparing (30%) and patchy inflammation (21%), which could theoretically confound initial assessment 5, 6
• Pediatric IBD shows less architectural distortion and inflammation compared to adults, potentially delaying diagnosis 6
• However, IBD does not cause true aganglionosis and would be distinguished by the presence of normal ganglion cells on biopsy 5

Critical Diagnostic Algorithm

1. Obtain rectal biopsy with acetylcholinesterase staining to confirm aganglionosis 3
2. If aganglionosis is confirmed, perform laparoscopic-assisted colonic mapping with full-thickness biopsies from multiple segments (sigmoid, transverse, ascending colon) to determine extent 4
3. Evaluate for coexistent neuronal dysplasias (IND, hypoganglionosis) on the same specimens 4, 3
4. If ganglion cells are present but abnormal, consider IND or hypoganglionosis; if absent throughout, diagnose TCA 3

Common Pitfalls to Avoid

• Failing to suspect Hirschsprung's disease in older children with chronic constipation and recurrent obstruction leads to diagnostic delay averaging years 1
• Relying solely on rectal suction biopsies may miss hypoganglionosis or variant forms of neuronal dysplasia 4
• Performing bowel resections without adequate proximal biopsies risks leaving aganglionic segments or resecting excessive bowel length 1
• TCA may lack the typical hypertrophic nerves seen in classic Hirschsprung's disease and can contain zonal areas with some ganglion cells, complicating diagnosis 3