Neonatal Hypoganglionosis Mimicking Hirschsprung Disease in a Resource-Limited Setting: A Case Report

Abstract

Background

Neonatal pediatric intestinal pseudo-obstruction (PIPO) is rare and may closely mimic Hirschsprung disease, particularly when caused by enteric neuropathies.

Case Presentation

We report the case of an 18-day-old female neonate who presented with delayed passage of meconium, persistent bilious vomiting, progressive abdominal distension, and significant weight loss since birth. Initial imaging demonstrated dilated bowel loops without evidence of mechanical obstruction. A rectal biopsy suggested distal aganglionosis, and a colostomy was performed. Despite anatomically appropriate diversion, the patient continued to have bilious gastric output, abdominal distension, and an inability to tolerate enteral feeds. Further surgical evaluation was therefore undertaken, and multi-level full-thickness intestinal biopsies were obtained. Histopathological analysis revealed a reduced density and abnormal morphology of ganglion cells within the myenteric plexus, consistent with hypoganglionosis, establishing the diagnosis of pediatric intestinal pseudo-obstruction (PIPO).

Conclusions

This case demonstrates how neonatal hypoganglionosis can follow a Hirschsprung-like diagnostic pathway yet fail to respond to diversion, underscoring the limitations of suction biopsy when clinical evolution is discordant with initial histological findings. Prolonged dependence on parenteral nutrition and limited access to advanced therapeutic options further illustrate the challenges of managing severe neonatal PIPO in resource-limited settings.

Introduction

Pediatric intestinal pseudo-obstruction (PIPO) is a rare and severe disorder characterized by chronic failure of gastrointestinal propulsion, leading to symptoms of intestinal obstruction in the absence of a mechanical lesion. ¹ Although previously grouped with adult chronic intestinal pseudo-obstruction (CIPO), PIPO is now recognized as a distinct pediatric entity with important differences in etiology, clinical course, and management. In contrast to adult CIPO, which is often secondary or acquired, PIPO is predominantly congenital and most commonly results from primary abnormalities of the enteric neuromusculature.^1-3

PIPO comprises a heterogeneous group of enteric neuromyopathies, with enteric neuropathies representing the most frequent pathological substrate in children.^1,4 Hypoganglionosis, defined by a reduced density of enteric ganglion cells, is an uncommon neuropathic variant within this spectrum. ⁵ Unlike Hirschsprung disease, in which ganglion cells are absent, hypoganglionosis involves partial neuronal deficiency and may therefore evade diagnosis using standard rectal suction biopsy techniques.^5,6

Neonatal-onset PIPO often presents with abdominal distension, feeding intolerance, and bilious vomiting, closely mimicking Hirschsprung disease both clinically and radiologically.^1,2 This overlap creates significant diagnostic challenges and may lead to inappropriate surgical interventions when enteric neuropathies are not considered. Importantly, surgical diversion or resection does not address the underlying neuromuscular dysfunction in PIPO and may worsen intestinal function.^1,5

Neonatal hypoganglionosis is particularly rare, with only limited cases reported in the literature, and remains an under-recognized cause of intestinal pseudo-obstruction in early life.^5,7 We report a neonatal case of PIPO due to hypoganglionosis that initially mimicked Hirschsprung disease, highlighting the diagnostic and therapeutic challenges associated with this condition and emphasizing the importance of accurate pathological evaluation in neonates with persistent obstructive symptoms.

Case Presentation

Initial Presentation and Early Neonatal Course

An 18-day-old female neonate was admitted to our Neonatal Intensive Care Unit (NICU) with persistent bilious vomiting, progressive abdominal distension, and significant weight loss since birth. She was born at term by repeat cesarean section after an uneventful pregnancy, with no perinatal complications. There was no family history of consanguinity or gastrointestinal disease.

On the first day of life, the patient developed bilious vomiting and failed to pass meconium until day four. Initial evaluation at an outside hospital revealed electrolyte abnormalities, including hyperkalemia (K 6.3 mmol/L), hyponatremia (Na 124 mmol/L), and hypochloremia (Cl 87 mmol/L). Imaging studies showed no evidence of mechanical obstruction. She was discharged home on specialized formula, however, symptoms persisted, with ongoing bilious vomiting, hypoactivity, and dependence on rectal stimulation for stool passage.

Admission to Our Institution (Day 18 of Life)

On admission to our center, the infant appeared cachectic but alert. Vital signs included a temperature of 37 °C, heart rate of 155 bpm, blood pressure of 62/57 mmHg, and random blood glucose of 127 mg/dL. Physical examination revealed a markedly distended but soft abdomen without organomegaly; otherwise, the examination was unremarkable. Abdominal distension was monitored clinically during admission.

Laboratory evaluation demonstrated severe hyponatremia (Na 115 mmol/L), hyperkalemia (K 6.1 mmol/L), hypochloremia (Cl 76 mmol/L), elevated blood urea nitrogen (86 mg/dL), mildly elevated bilirubin levels (total 2.6 mg/dL, direct 0.9 mg/dL), leukocytosis (WBC 22.8 × 10³/µL, neutrophils 41%), thrombocytosis (platelets 681 × 10³/µL), and preserved renal function (creatinine 0.8 mg/dL). C-reactive protein was 0.85 mg/L. A plain abdominal radiograph (Figure 1) demonstrated diffuse colonic distension without signs of mechanical obstruction. A gastrografin enema showed colonic dilatation with delayed stool evacuation.

Figure 1.

Plain abdominal radiograph demonstrating diffuse bowel dilatation in a neonate with intestinal obstruction

Initial Diagnostic Evaluation and Management

Given the clinical picture of neonatal-onset functional obstruction without a mechanical cause, the differential diagnosis included Hirschsprung disease, congenital intestinal pseudo-obstruction, sepsis-associated ileus, necrotizing enterocolitis, metabolic or mitochondrial disorders, autoimmune enteropathy, and medication-related dysmotility.

The patient was managed with nasogastric decompression, bowel rest, correction of electrolyte abnormalities, and initiation of total parenteral nutrition (TPN). Intravenous fluid therapy was administered with careful adjustment according to electrolyte monitoring and fluid balance. TPN was initiated through central venous access and adjusted according to daily clinical and metabolic requirements. Empirical broad-spectrum antibiotics (ampicillin, gentamicin, and metronidazole) were initiated and rectal and colonic biopsies were planned to evaluate for Hirschsprung disease.

Initial Surgical Intervention

Serial intraoperative frozen-section biopsies demonstrated absence of ganglion cells in the rectum with preserved ganglion cells proximally, consistent with distal aganglionosis. Based on these findings, a diverting colostomy was performed.

Clinical Decision-Making and Re-Evaluation

Full-thickness intestinal biopsies were not obtained during the initial operation, as rectal suction and leveling biopsies are the standard first-line diagnostic approach when Hirschsprung disease is suspected. However, despite anatomically appropriate diversion, the patient showed no clinical improvement postoperatively, with persistent bilious nasogastric output, progressive abdominal distension, and minimal stool output. Mechanical obstruction was excluded by postoperative imaging.

The persistence of obstructive symptoms despite adequate diversion raised concern for an underlying diffuse enteric neuromuscular disorder. Given the failure of expected clinical improvement and the exclusion of mechanical causes, a decision was made to proceed with reoperation for further evaluation and definitive diagnosis.

Second Surgical Intervention and Final Diagnosis

An ileal resection with ileostomy was performed. Full-thickness biopsies were obtained from multiple intestinal segments. Histopathological examination demonstrated reduced ganglion cell density, immature morphology of ganglion cells, and abnormal distribution within the myenteric plexus, findings consistent with hypoganglionosis. The diagnosis was supported by concordant interpretation at external reference laboratories, confirming enteric neuropathy as the underlying cause of congenital intestinal pseudo-obstruction.

Clinical Course and Outcome

Postoperatively, the patient remained dependent on prokinetic therapy and cyclic TPN, with an inability to tolerate enteral feeds. Electrolyte abnormalities were corrected during hospitalization; however, abdominal distension and feeding intolerance remained persistent throughout the observed clinical course. She required long-term central venous access and experienced recurrent catheter-related bloodstream infections, including Klebsiella species. Intestinal transplantation is reserved for highly selected end-stage cases and was neither indicated nor available in our setting. Genetic evaluation was not performed, as advanced molecular testing was not available locally during the patient’s management. Follow-up remains ongoing, with continued dependence on supportive nutritional management. Figure 2 summarizes the clinical course of the patient (Figure 2).

Figure 2.

Clinical timeline of diagnostic evaluation, surgical interventions, and disease course

Discussion

Pediatric intestinal pseudo-obstruction (PIPO) is a rare and severe disorder of gastrointestinal motility, particularly when it presents in the neonatal period. It is characterized by functional intestinal obstruction in the absence of a mechanical lesion and is most commonly caused by primary abnormalities of the enteric neuromusculature, including neuropathic and myopathic processes.^1-4,8,9 Hypoganglionosis represents an uncommon neuropathic subtype within this spectrum, defined by a reduced density and abnormal morphology of enteric ganglion cells, and remains infrequently reported in neonates.^2,5,10,11

This case highlights the diagnostic challenges associated with early-onset PIPO and its frequent clinical overlap with Hirschsprung disease. Our patient presented with delayed passage of meconium, progressive abdominal distension since birth, and persistent bilious vomiting, features that appropriately prompted evaluation for Hirschsprung disease. Initial rectal biopsy suggested distal aganglionosis, leading to colostomy formation. However, the absence of clinical improvement following anatomically appropriate diversion raised suspicion for a diffuse motility disorder rather than an isolated distal obstructive lesion. Similar diagnostic trajectories, in which enteric neuromuscular disorders are only considered after unsuccessful surgery, have been described in pediatric reports.^7,11

Definitive diagnosis in our patient required full-thickness intestinal biopsies obtained from multiple bowel segments, which demonstrated reduced density and immature ganglion cells within the myenteric plexus, consistent with hypoganglionosis. This finding underscores a well-recognized limitation of rectal suction biopsy, which is highly effective for diagnosing Hirschsprung disease but cannot reliably detect disorders characterized by partial neuronal loss or abnormalities confined to the myenteric plexus.^5,6,10,11 When the clinical course is discordant with initial histological findings or when symptoms persist despite appropriate diversion, early consideration of full-thickness sampling is essential.

The diagnostic differences between rectal suction biopsy and full-thickness intestinal biopsy, and their respective roles in Hirschsprung disease and PIPO, are summarized in Table 1.

Table 1.

Comparison of Rectal Suction Biopsy and Full-Thickness Intestinal Biopsy in the Evaluation of Neonatal Intestinal Obstruction^5,6,10,11

Feature	Rectal suction biopsy	Full-thickness intestinal biopsy
Invasiveness	Minimally invasive, bedside procedure	Surgical procedure requiring anesthesia
Tissue Layers Assessed	Mucosa and submucosa	Mucosa, submucosa, myenteric plexus, and muscularis propria
Primary Clinical Role	First-line test for suspected Hirschsprung disease	Definitive evaluation of enteric neuromuscular disorders
Ability to Diagnose Aganglionosis	High sensitivity	High sensitivity
Ability to Diagnose Hypoganglionosis	Limited	Reliable
Ability to Assess Ganglion Cell Density and Morphology	Limited	Comprehensive
Ability to Evaluate Interstitial Cells of Cajal and Smooth Muscle	No	Yes
Diagnostic Utility in PIPO	Screening only	Definitive diagnostic test
Key Limitation	May miss partial or proximal neuropathies	Requires operative intervention

From a management perspective, it is important to emphasize that PIPO is treated primarily through supportive and nutritional strategies rather than curative surgical intervention. Long-term parenteral nutrition, individualized enteral feeding approaches, prevention and treatment of small intestinal bacterial overgrowth, and the use of prokinetic agents constitute the cornerstone of management.^2,8,9 Surgical interventions, including decompressive gastrostomy, jejunostomy, ileostomy, or colostomy, may be beneficial in selected patients for symptom relief or intestinal decompression but do not correct the underlying motility disorder.^8,9,12 Large pediatric series demonstrate that decompressive stomas can provide partial or temporary symptom improvement in selected cases, although outcomes remain variable and the disease burden remains substantial.^9,12

Home parenteral nutrition represents a key component in the long-term management of intestinal failure and has been associated with improved survival and quality of life. However, its implementation in resource-limited settings remains challenging due to financial constraints, limited infrastructure, need for caregiver training, and increased risk of catheter-related complications. In our setting, these limitations significantly affect the feasibility of long-term home-based management.

Intestinal transplantation is not a curative treatment for PIPO and should be considered only in highly selected patients with end-stage intestinal failure, life-threatening complications of long-term parenteral nutrition, or loss of central venous access, and is performed only in specialized tertiary centers^1,2,12; In our patient, these criteria were not met, and management remained primarily supportive. Many children with PIPO survive into childhood and adulthood with optimized medical and nutritional management, although long-term dependence on parenteral nutrition is common, particularly in neonatal-onset disease.^2,8,9,12

In our patient, persistent dependence on parenteral nutrition, recurrent catheter-related bloodstream infections, and failure of enteral feeding trials reflected the severity of the disease. Management was further complicated by the challenges of long-term parenteral nutrition in a resource-limited setting. This highlights an important global health issue: in such settings, clinicians must balance the risks of prolonged parenteral nutrition with limitations in resources and supportive care. Such contexts emphasize the importance of early and accurate diagnosis, avoidance of unnecessary surgery, and optimization of supportive care.

By detailing the complete diagnostic and therapeutic course of neonatal hypoganglionosis, this case highlights important diagnostic challenges, particularly the limitations of rectal suction biopsy and the consequences of discordant clinical evolution, as well as the impact of resource limitations on management. PIPO should be considered in neonates with persistent obstructive symptoms despite anatomically appropriate diversion, and reliance on rectal suction biopsy alone may be insufficient when the clinical course is atypical. Early use of full-thickness biopsy can clarify the diagnosis, guide management, and potentially prevent repeated ineffective surgical interventions.

Conclusion

In summary, this case highlights three important clinical lessons. First, persistent obstructive symptoms following anatomically appropriate diversion in neonates should prompt early consideration of motility disorders, particularly pediatric intestinal pseudo-obstruction. Second, full-thickness, multi-level intestinal biopsies play a key role in distinguishing hypoganglionosis from aganglionosis and may help prevent repeated or ineffective surgical interventions when the clinical course is discordant with initial histological findings. Third, although PIPO is primarily managed through long-term medical and nutritional support, its management remains particularly challenging in resource-limited settings. Reporting real-world experiences from resource-limited settings is therefore essential to expand the limited literature and to improve awareness, diagnosis, and management of rare, high-risk conditions such as neonatal PIPO.