An 18-year-old patient with lifelong skin ulcers and severe anemia was found to have two extremely rare conditions simultaneously: prolidase deficiency (a genetic disorder affecting collagen breakdown) and celiac disease (an immune reaction to gluten). According to Gram Research analysis of this case report, genetic testing identified a specific PEPD gene mutation causing the prolidase deficiency, while blood tests and intestinal biopsy confirmed celiac disease. After six months of treatment combining a gluten-free diet, iron, vitamin C, manganese, and L-proline supplementation, the patient experienced significant healing of skin ulcers and improvement in blood cell counts, demonstrating that identifying and treating both conditions simultaneously was more effective than treating celiac disease alone.
A case report describes an 18-year-old patient who had two extremely rare conditions at the same time: prolidase deficiency (a genetic disorder affecting how the body breaks down collagen) and celiac disease (an autoimmune condition triggered by gluten). The patient suffered from non-healing skin ulcers, repeated infections, and severe anemia for years before doctors discovered both diseases. According to Gram Research analysis, genetic testing revealed a specific gene mutation causing the prolidase deficiency, while blood tests and intestinal biopsy confirmed celiac disease. After treatment with supplements, vitamins, and a gluten-free diet, the patient’s skin ulcers significantly improved within six months. This case highlights how rare genetic disorders can hide behind more common conditions, making diagnosis challenging.
Key Statistics
A 2026 case report documented an 18-year-old patient with the rare combination of prolidase deficiency and celiac disease, conditions that coexist so infrequently that their simultaneous occurrence is considered extraordinarily rare in medical literature.
Genetic testing revealed a homozygous pathogenic splice site mutation (c.504-2A > G) in the PEPD gene in the patient, confirming prolidase deficiency as the underlying cause of lifelong non-healing skin ulcers and recurrent infections.
Within six months of comprehensive treatment including a gluten-free diet, iron, vitamin C, manganese, and L-proline supplementation, the patient demonstrated significant healing of skin ulcers and substantial improvement in blood cell counts, suggesting that multidisciplinary management of both conditions was essential for clinical improvement.
The Quick Take
- What they studied: How a young man with lifelong skin ulcers, infections, and anemia was finally diagnosed with two rare conditions happening at the same time
- Who participated: One 18-year-old male patient of Asian Indian descent living in a rural area with a lifelong history of skin problems and health complications
- Key finding: Genetic testing identified a rare mutation in the PEPD gene causing prolidase deficiency, which was occurring alongside celiac disease. After six months of targeted treatment including supplements and a gluten-free diet, the patient’s skin ulcers healed significantly and blood counts improved
- What it means for you: If you have chronic skin ulcers, repeated infections, and anemia that don’t improve with standard treatment, doctors should consider rare genetic disorders. Genetic testing can help identify hidden conditions, though this case is extremely rare and most people with these symptoms have more common causes
The Research Details
This is a case report, which means doctors documented the medical story of one patient in detail. The 18-year-old patient had suffered from open skin sores his entire life, along with repeated infections and severe anemia requiring blood transfusions starting at age 15. Doctors initially diagnosed him with celiac disease (an immune reaction to gluten in food) based on blood tests and a biopsy of his small intestine. However, his symptoms continued even after he stopped eating gluten.
Because the patient wasn’t improving as expected, doctors performed genetic testing called clinical exome sequencing, which reads the patient’s DNA to find mutations. This revealed a specific genetic mutation in the PEPD gene that causes prolidase deficiency—a condition so rare that most doctors rarely see it. The patient then received treatment combining a gluten-free diet, iron and vitamin C supplements (to help with anemia), manganese, and L-proline powder (an amino acid that helps with collagen and skin healing).
The doctors tracked the patient’s progress over six months, documenting improvements in skin healing and blood cell counts.
Case reports are important because they describe unusual situations that doctors might not encounter in their regular practice. When two extremely rare conditions occur together, it’s even more unusual. By publishing this case, the doctors help other medical professionals recognize similar patterns and avoid diagnostic delays. This approach is especially valuable for rare genetic disorders that might be overlooked if doctors only look for common conditions.
This is a single case report, which means it describes one patient’s experience rather than comparing many patients. While case reports are valuable for raising awareness about rare conditions, they cannot prove that a treatment works for everyone with the same condition. The patient did improve significantly, but we cannot know if others with prolidase deficiency would respond the same way. The diagnosis was confirmed with genetic testing, which is the gold standard for identifying genetic mutations, making the prolidase deficiency diagnosis reliable. However, the small sample size means these findings should be viewed as illustrative rather than definitive evidence.
What the Results Show
The patient presented with a lifelong history of non-healing skin ulcers covering large areas of his body, recurrent infections, and chronic diarrhea. At age 15, he developed severe anemia (low red blood cells) requiring multiple blood transfusions. Initial investigations showed elevated antibodies against tissue transglutaminase, and a biopsy of his small intestine showed villous atrophy (flattened finger-like structures that normally absorb nutrients), confirming celiac disease.
Despite starting a strict gluten-free diet, the patient’s skin ulcers and other symptoms did not improve significantly. This prompted genetic testing, which revealed a homozygous pathogenic splice site mutation in the PEPD gene (specifically c.504-2A > G), confirming prolidase deficiency. This mutation means the patient inherited the same defective gene from both parents, completely eliminating the enzyme prolidase, which is essential for breaking down collagen in the body.
After diagnosis, the patient received comprehensive treatment including dietary modifications (gluten-free diet), iron supplementation, vitamin C, manganese, and oral L-proline powder. At the six-month follow-up, significant healing of the skin ulcers was documented, and his blood cell counts improved substantially. The combination of treating both conditions simultaneously appeared to be more effective than treating celiac disease alone.
The case demonstrates that the presence of celiac disease may have masked or complicated the diagnosis of prolidase deficiency. Both conditions affect nutrient absorption and can cause anemia and gastrointestinal symptoms. The patient’s improvement after addressing both conditions suggests that multidisciplinary management targeting the underlying causes is more effective than treating symptoms alone. The addition of L-proline supplementation, which provides building blocks for collagen synthesis, appeared particularly important for skin healing.
Prolidase deficiency is an extremely rare autosomal recessive disorder, with only a handful of cases reported in medical literature worldwide. Most documented cases present with recurrent skin ulcers and infections, consistent with this patient’s presentation. Celiac disease is much more common, affecting approximately 1 in 100 people globally, but the coexistence of both conditions in one patient is extraordinarily rare and has not been well-documented in medical literature. This case adds to our understanding of how rare genetic disorders can coexist with more common autoimmune conditions, potentially complicating diagnosis and treatment.
This is a single case report describing one patient, so the findings cannot be generalized to all people with prolidase deficiency or celiac disease. We cannot determine whether the improvement was due to treating the prolidase deficiency, the celiac disease, or the combination of both. The patient’s ethnic background and rural living conditions may have influenced disease presentation or access to care, limiting applicability to other populations. Long-term follow-up data beyond six months is not provided, so we don’t know if improvements were sustained. Finally, the specific combination of supplements and treatments was tailored to this individual patient, and we cannot assume the same approach would work for others with prolidase deficiency.
The Bottom Line
For patients with chronic, non-healing skin ulcers combined with recurrent infections and anemia that don’t respond to standard treatments, doctors should consider genetic testing to identify rare metabolic disorders (moderate confidence—based on one case). A gluten-free diet is essential for anyone with confirmed celiac disease (high confidence—well-established). Supplementation with vitamin C, iron, manganese, and L-proline may support skin healing in prolidase deficiency, though more research is needed (low confidence—based on one patient’s response). Multidisciplinary care involving dermatologists, gastroenterologists, and genetic specialists is recommended for complex cases with overlapping conditions (moderate confidence—based on clinical reasoning).
This case is most relevant to medical professionals who care for patients with chronic skin conditions, recurrent infections, or unexplained anemia. Patients with lifelong skin ulcers that haven’t responded to conventional treatment should discuss genetic testing with their doctors. Family members of someone with prolidase deficiency should be aware that it’s an inherited condition. However, because prolidase deficiency is extremely rare, most people with skin ulcers or anemia have other, more common causes that should be investigated first.
In this case, significant skin healing was observed within six months of starting comprehensive treatment. However, this timeline may not apply to all patients with prolidase deficiency. The patient’s improvement suggests that early diagnosis and treatment initiation are important, but individual responses to treatment will vary. Long-term management and monitoring are likely necessary for sustained improvement.
Frequently Asked Questions
What is prolidase deficiency and how rare is it?
Prolidase deficiency is an extremely rare genetic disorder where the body cannot properly break down collagen due to a mutation in the PEPD gene. Only a handful of cases have been reported worldwide. It causes chronic skin ulcers, recurrent infections, and blood abnormalities. Most people will never encounter this condition.
Can you have celiac disease and another condition at the same time?
Yes, people can have multiple conditions simultaneously, though the combination of celiac disease with prolidase deficiency is extraordinarily rare. When two conditions coexist, symptoms may overlap and complicate diagnosis. This case demonstrates why doctors should consider rare genetic disorders when patients don’t improve with standard treatment.
How is prolidase deficiency diagnosed?
Prolidase deficiency is diagnosed through genetic testing called clinical exome sequencing, which reads a patient’s DNA to identify mutations in the PEPD gene. This test is typically ordered when patients have unexplained chronic skin ulcers, recurrent infections, and blood abnormalities that don’t respond to conventional treatment.
What supplements help with prolidase deficiency?
In this case, the patient improved with L-proline powder (an amino acid building block for collagen), vitamin C (which supports collagen synthesis), iron (for anemia), and manganese. However, this is based on one patient’s response. Treatment should be individualized and supervised by healthcare providers familiar with rare metabolic disorders.
How long does it take to see improvement in skin ulcers with treatment?
In this case report, significant skin healing was observed within six months of starting comprehensive treatment. However, individual responses vary considerably. Early diagnosis and prompt treatment initiation appear important, but long-term management and monitoring are typically necessary for sustained improvement.
Want to Apply This Research?
- Users with chronic skin conditions should photograph ulcers weekly in consistent lighting and track wound size measurements (length × width in centimeters) to document healing progress. Record any new infections, fever episodes, and energy levels daily. Track dietary adherence to gluten-free diet with a simple yes/no daily log.
- For users managing celiac disease, use the app to scan food barcodes and identify gluten-containing products before purchase. Set daily reminders for supplement intake (vitamin C, iron, manganese, L-proline). Log skin care routines and note which treatments correlate with improved healing. Create a symptom diary linking diet, supplements, and skin/infection status.
- Establish a baseline by documenting current ulcer status, infection frequency, and energy levels for two weeks. Then track weekly changes in wound appearance, monthly blood work results (if available), and quarterly photos for visual comparison. Set monthly check-in reminders to review trends and adjust tracking if needed. Share data with healthcare providers during appointments to inform treatment adjustments.
This case report describes one patient’s experience with an extremely rare combination of conditions. The findings cannot be applied to all people with prolidase deficiency or celiac disease. If you have chronic skin ulcers, recurrent infections, or unexplained anemia, consult with a qualified healthcare provider for proper diagnosis and treatment. Genetic testing should only be performed under medical supervision. Do not start any supplements or dietary changes without discussing them with your doctor first. This article is for educational purposes and should not replace professional medical advice.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.