Can longstanding constipation be associated with muscular dystrophy or other muscle and mitochondrial disorders?

Association Between Longstanding Constipation and Muscular Dystrophy/Mitochondrial Disorders

Yes, longstanding constipation can be associated with muscular dystrophy and mitochondrial disorders, as these conditions can affect gastrointestinal smooth muscle function and motility.

Muscular Dystrophy and GI Dysfunction

• Muscular dystrophies are frequently associated with gastrointestinal motility disorders, including chronic constipation and more severe conditions like intestinal pseudo-obstruction 1
• Duchenne muscular dystrophy (DMD) specifically has been linked to GI smooth muscle dysfunction, which can manifest as gastroparesis, intestinal dysmotility, and constipation 2
• In myotonic dystrophy, there are documented cases of chronic intestinal pseudo-obstruction (CIPOS), which represents a severe form of GI dysmotility 3

Mitochondrial Disorders and GI Dysfunction

• Mitochondrial disorders are relatively common in patients with chronic intestinal pseudo-obstruction (CIPO) - one study showed 19% of adult patients labeled as CIPO had mitochondrial disorders 2
• Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is characterized by severe gastrointestinal dysmotility, with recurrent diarrhea and symptoms of obstruction 2
• Patients with MNGIE typically present between the first and third decade of life and have gastrointestinal dysmotility as the most prominent manifestation 2

Diagnostic Approach for Suspected Cases

When longstanding constipation raises suspicion for muscular dystrophy or mitochondrial disorders, consider:

1. Initial screening tests:

   • Screen for hypothyroidism, coeliac disease, and diabetes 2
   • Assess for proximal muscle weakness and check muscle enzyme levels 4

2. Specific tests for mitochondrial disorders:

   • Plasma and urine thymidine and deoxyuridine
   • White blood cell thymine phosphorylase
   • Testing for the TYMP gene
   • Screening for related diseases like MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) 2

3. Advanced diagnostic procedures:

   • Muscle biopsy and sequencing of mitochondrial genome 2
   • MRI brain can be helpful in the diagnosis of MNGIE 2
   • Full thickness jejunal biopsy to assess enteric nerves and muscle 2

Pathophysiological Mechanisms

• In muscular dystrophies, gastrointestinal dysmotility occurs due to dysfunction of gastrointestinal smooth muscle 5
• Mitochondrial dysfunction leads to inflammation, fibrosis, and metabolic anomalies that can affect gut function 6
• The gut-muscle axis may be involved in the spread of inflammatory signals to muscles in muscular dystrophies 6
• Intestinal dysbiosis can modulate the metabolic state, immune response, and mitochondrial biogenesis in muscular dystrophies 6

Clinical Considerations and Management

• Patients with DMD require special attention to GI function, particularly in perioperative settings, as they may have increased risk of complications 2
• Management approaches include:
  • Bowel regimens to avoid and treat constipation 2
  • Consideration of prokinetic GI medications 2
  • Gastric decompression with a nasogastric tube in patients with severe GI dysmotility 2
  • Nutritional support if oral feeding is compromised 2

Common Pitfalls and Caveats

• Constipation alone is not diagnostic of muscular dystrophy or mitochondrial disorders - look for additional neurological or systemic symptoms 2
• GI dysmotility in these disorders can range from mild constipation to life-threatening conditions like intestinal pseudo-obstruction and volvulus 1
• Medications used to treat other symptoms in these patients (particularly pain medications) can exacerbate constipation 2
• Mitochondrial disorders are often underdiagnosed and should be considered in patients with unexplained constellation of symptoms involving seemingly unrelated organs 2