Hirschsprung disease type 2

Hirschsprung's disease type 2 (HD2) is a rare and severe form of Hirschsprung's disease (HD), a congenital condition characterized by the absence of ganglion cells in the intestinal wall, specifically in the colon. This absence leads to a blockage of the intestine, preventing normal bowel movements. HD2 is distinguished from the more common form of Hirschsprung's disease by its genetic causes and clinical manifestations.

Etiology and Genetics

HD2 is caused by mutations in specific genes that are crucial for the development of the enteric nervous system, the part of the nervous system that controls the gastrointestinal tract. The most commonly implicated gene in HD2 is the RET proto-oncogene, although mutations in other genes have also been associated with the disease. These genetic mutations are typically inherited in an autosomal dominant manner, meaning only one copy of the altered gene is necessary to increase the risk of the disease. However, many cases of HD2 occur due to new mutations in the gene and are not inherited from a parent.

Pathophysiology

The pathophysiology of HD2 involves the failure of neural crest cells to migrate, proliferate, and differentiate into ganglion cells in the distal colon. This leads to a segment of the bowel that lacks the necessary nerve cells to orchestrate the movement of digested material through the intestine, causing a functional obstruction known as intestinal aganglionosis.

Clinical Features

Patients with HD2 typically present in the neonatal period with symptoms of intestinal obstruction, such as failure to pass meconium within the first 48 hours of life, abdominal distension, vomiting, and constipation. In some cases, enterocolitis, a life-threatening inflammation of the colon, can develop, presenting with fever, lethargy, and bloody diarrhea.

Diagnosis

The diagnosis of HD2 is based on clinical presentation and confirmed by diagnostic tests. A barium enema may show a transition zone between the normal and affected segments of the colon. The definitive diagnosis is made through a rectal biopsy, which shows the absence of ganglion cells in the affected segment of the colon.

Treatment

The treatment for HD2 involves surgical removal of the aganglionic segment of the bowel. The most commonly performed surgery is the pull-through procedure, which involves pulling the healthy, ganglionated part of the colon down to the anus and connecting it there, bypassing the affected segment. Postoperative care is crucial for managing complications and ensuring proper bowel function.

Prognosis

The prognosis for patients with HD2 who receive timely and appropriate treatment is generally good. Surgical intervention can significantly improve symptoms and quality of life. However, long-term follow-up is necessary to manage potential complications, such as enterocolitis, constipation, and incontinence.