A new genetic mutation in the PIGO gene caused both Mabry syndrome, a rare developmental disorder, and Hirschsprung’s disease, a bowel condition, in a single two-year-old patient. According to Gram Research analysis, this case report reveals that Mabry syndrome can affect the digestive system more often than previously recognized, with the patient showing developmental delays, high alkaline phosphatase levels (613 IU/L), seizures, and missing nerve cells in the bowel that required surgery to correct.
Mabry syndrome is an extremely rare genetic condition that affects how the brain develops and causes high levels of an enzyme called alkaline phosphatase in the blood. According to Gram Research analysis, doctors in Turkey discovered a new genetic mutation in a young patient that caused not only the typical brain and developmental problems of Mabry syndrome, but also Hirschsprung’s disease, a serious bowel condition where nerve cells don’t form properly in the intestines. This case is important because it shows that Mabry syndrome can affect more parts of the body than previously thought, and it highlights why genetic testing is crucial when children have unusual combinations of developmental and digestive problems.
Key Statistics
A case report from Turkey in 2026 documented a two-year-old boy with a novel homozygous PIGO gene mutation (p.Arg445Pro) who presented with both Mabry syndrome and Hirschsprung’s disease, showing that these two rare conditions can occur together.
The patient had severely elevated alkaline phosphatase levels at 613 IU/L, which is significantly higher than normal, along with developmental delays, seizures, and severe constipation unresponsive to medical treatment.
After surgical removal of the affected bowel segment, the patient achieved spontaneous bowel function with only rare episodes of enterocolitis, demonstrating that recognizing and treating the gastrointestinal component improves outcomes.
The Quick Take
- What they studied: A single case of a young boy with Mabry syndrome, a rare genetic disorder, who also had Hirschsprung’s disease, a condition where the nerves that control bowel movements don’t develop properly.
- Who participated: One two-year-old boy from Turkey with developmental delays, seizures, and digestive problems. His parents were tested and found to carry one copy of the same genetic mutation.
- Key finding: Doctors discovered a new mutation in the PIGO gene (p.Arg445Pro) that caused both Mabry syndrome and Hirschsprung’s disease in the same patient, showing these conditions can occur together more often than previously recognized.
- What it means for you: If a child has unusual developmental delays combined with severe constipation or bowel problems, genetic testing should be considered. This case reminds doctors to look for multiple conditions at once rather than treating symptoms separately. However, this is an extremely rare condition, so it should not cause alarm in most families.
The Research Details
This is a case report, which means doctors documented the medical history and findings from one patient in detail. The two-year-old boy came to the hospital with developmental problems like not responding to his name and poor muscle control. Doctors ran many tests including blood work, brain imaging, and brain wave recordings, but found nothing unusual in these standard tests.
Because the common tests didn’t explain his symptoms, doctors used whole exome sequencing, a genetic test that reads the instructions in a person’s DNA. This advanced test found a mutation in the PIGO gene, a gene that helps cells function properly. The doctors then tested the parents and found they each carried one copy of this same mutation, which explained how their son inherited two copies (one from each parent).
The patient also had severe constipation since birth that didn’t respond to medicines. A biopsy, a small tissue sample from the rectum, showed that nerve cells were missing, confirming Hirschsprung’s disease. After surgery to remove the affected bowel section, the boy’s bowel function improved significantly.
This research approach matters because it shows how genetic testing can solve medical mysteries when standard tests come back normal. By using whole exome sequencing, doctors could identify the root cause of the boy’s symptoms and connect two seemingly separate conditions. This helps other doctors recognize that Mabry syndrome can involve the digestive system, not just the brain and nervous system.
As a case report of a single patient, this study provides detailed clinical information but cannot prove that all patients with this mutation will have the same symptoms. The strength of this report is the thorough documentation and the discovery of a new genetic variant. The limitation is that one case cannot establish how common this combination is or predict outcomes for other patients. The genetic testing was rigorous and confirmed by multiple methods, which increases confidence in the genetic finding.
What the Results Show
The patient presented with developmental delays, including poor responsiveness to his environment and inability to control his trunk muscles. Blood tests showed very high alkaline phosphatase levels (613 IU/L, which is significantly elevated). At 11 months old, the child experienced a seizure without fever. Standard tests including brain imaging and brain wave recordings appeared normal, which initially made diagnosis difficult.
Genetic testing revealed a homozygous mutation in the PIGO gene, meaning the child inherited two copies of the same genetic error (one from each parent). This specific mutation, p.Arg445Pro, had not been previously documented in medical literature, making it a novel finding. Both parents carried one copy of the mutation but did not show symptoms, which is typical for recessive genetic conditions.
The patient also had severe constipation from birth that did not respond to medical treatment. Physical examination revealed abdominal swelling and abnormal bowel function. A rectal biopsy confirmed Hirschsprung’s disease by showing the absence of nerve cells in the bowel tissue. After surgical removal of the affected bowel section, the patient achieved normal bowel function with only rare complications.
The case demonstrates that Mabry syndrome, previously thought to primarily affect the nervous system, can include gastrointestinal complications. The patient’s combination of neurological symptoms (developmental delay, seizures, muscle weakness) with digestive problems (Hirschsprung’s disease) suggests that PIGO gene mutations may affect multiple body systems. The successful surgical outcome for the bowel condition shows that recognizing and treating the gastrointestinal component is important for overall patient health.
Mabry syndrome was first described as a condition affecting brain development, muscle tone, and causing high alkaline phosphatase levels. This case expands the known features of Mabry syndrome by documenting its association with Hirschsprung’s disease. While previous reports mentioned that gastrointestinal problems could occur with Mabry syndrome, this case provides detailed documentation of how to diagnose and treat this combination. The discovery of a new PIGO gene mutation also adds to the growing understanding of how different genetic changes in this gene can cause disease.
This is a single case report, so the findings apply only to this one patient. We cannot determine from one case how often this combination occurs or whether all patients with this specific mutation will have the same symptoms. The study does not include a control group or comparison to other patients. Additionally, long-term follow-up information beyond the immediate post-surgical period is not provided, so we don’t know the patient’s long-term outcomes. Rare genetic conditions often have variable presentations, so other patients with similar mutations may have different symptoms.
The Bottom Line
For healthcare providers: Consider genetic testing in children with developmental delays combined with unexplained gastrointestinal problems, especially when standard tests are normal. Screen for Hirschsprung’s disease in patients diagnosed with Mabry syndrome. For families: If a child has unusual combinations of developmental and digestive problems, request genetic evaluation. This is a very rare condition, so most children with these symptoms will have different causes. Confidence level: Moderate, based on this single case and existing knowledge of Mabry syndrome.
Pediatricians and neurologists should be aware that Mabry syndrome can include bowel problems. Families with children who have developmental delays and severe constipation should discuss genetic testing with their doctors. Parents who are carriers of PIGO mutations may want genetic counseling if planning to have more children. This information is not relevant to the general population, as Mabry syndrome is extremely rare.
Symptoms of Mabry syndrome typically appear in infancy, as seen in this case. Developmental delays and seizures may be noticed within the first year of life. Bowel problems may be present from birth or develop early. Genetic testing can provide answers within weeks to months. Surgical treatment for Hirschsprung’s disease, when present, can improve bowel function relatively quickly, though full recovery may take several months.
Frequently Asked Questions
What is Mabry syndrome and what causes it?
Mabry syndrome is an extremely rare genetic disorder caused by mutations in the PIGO gene. It causes developmental delays, distinctive facial features, weak muscle tone, high alkaline phosphatase enzyme levels in blood, and seizures. This case shows it can also include Hirschsprung’s disease affecting the bowel.
Can Mabry syndrome affect the digestive system?
Yes, this case report demonstrates that Mabry syndrome can be associated with Hirschsprung’s disease, a condition where nerve cells don’t develop properly in the bowel, causing severe constipation. This combination had not been well-documented before, highlighting the need for doctors to screen for gastrointestinal problems in Mabry syndrome patients.
How is Hirschsprung’s disease diagnosed and treated?
Hirschsprung’s disease is diagnosed through a rectal biopsy, which shows the absence of nerve cells in the bowel tissue. Treatment involves surgery to remove the affected section of bowel. In this case, surgery successfully restored normal bowel function, though the patient experienced rare complications afterward.
Why is genetic testing important for rare developmental disorders?
Genetic testing can identify the root cause when standard tests like brain imaging and blood work appear normal. In this case, whole exome sequencing discovered the PIGO gene mutation that explained both the neurological and digestive symptoms, allowing doctors to provide appropriate treatment and genetic counseling to the family.
How common is Mabry syndrome?
Mabry syndrome is extremely rare, with only a handful of cases documented in medical literature. This case report adds to the limited knowledge about the condition and shows that genetic variations can cause different combinations of symptoms, making each case potentially unique.
Want to Apply This Research?
- For families with affected children: Track developmental milestones (first smile, sitting up, speaking words), seizure frequency and duration, alkaline phosphatase blood levels at each test, and bowel function patterns including frequency of constipation episodes and medication effectiveness.
- Parents can use an app to log daily bowel movements, note any signs of bowel obstruction or enterocolitis (fever, severe abdominal pain, explosive diarrhea), record seizure occurrences with time and duration, and document developmental progress. This information helps doctors monitor the condition and adjust treatment.
- Establish a baseline of normal function for the individual child, then track changes over time. Set reminders for scheduled blood tests to monitor alkaline phosphatase levels. Create alerts for concerning symptoms like fever combined with abdominal pain or changes in seizure patterns. Share tracked data with healthcare providers at each visit to inform treatment decisions.
This article describes a single rare case and is for educational purposes only. Mabry syndrome is an extremely rare condition that requires specialized medical care. If you suspect your child has developmental delays, seizures, or severe constipation, consult with a pediatrician or pediatric neurologist for proper evaluation and diagnosis. Genetic testing should only be performed under medical supervision. This information should not be used for self-diagnosis or to replace professional medical advice. Always seek guidance from qualified healthcare providers for any medical concerns.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.