A teenager spent 13 years struggling with dangerously high cholesterol that wouldn’t improve with normal treatments. Doctors initially thought she had a common inherited cholesterol condition, but genetic testing revealed she actually had a rare disease called sitosterolemia—caused by an unusual genetic quirk where she inherited two copies of a faulty gene from her father. Once doctors understood the real problem, they switched her treatment to avoid certain plant oils and added a specific medication. Within four months, her cholesterol levels returned to normal and her symptoms improved dramatically. This case shows why genetic testing can be a game-changer for patients whose cholesterol doesn’t respond to standard treatments.
The Quick Take
- What they studied: How genetic testing helped identify the true cause of a teenager’s treatment-resistant high cholesterol and led to successful treatment
- Who participated: One teenage patient (female) who had suffered from extremely high cholesterol since age two, despite being on standard cholesterol medications and diet restrictions for 13 years
- Key finding: Genetic sequencing revealed the patient had sitosterolemia (a rare genetic disease affecting how the body handles plant sterols) rather than the initially suspected familial hypercholesterolemia. Switching to targeted treatment normalized cholesterol levels within 4 months
- What it means for you: If you or a family member has high cholesterol that doesn’t improve with standard medications and diet changes, genetic testing may reveal a different underlying cause that responds to different treatment. This is especially important for young people with severe cholesterol problems
The Research Details
This is a case report, which means doctors documented the medical history and treatment of one specific patient in detail. The patient was a girl who developed fatty bumps under her skin (xanthomas) at age two, a sign of very high cholesterol. For 13 years, she took statin medications (the standard cholesterol drugs) and followed a strict low-cholesterol diet, but her cholesterol levels stayed dangerously high. At age 15, doctors performed genome sequencing—a test that reads all the genetic instructions in her cells—to search for genetic causes of her treatment-resistant condition.
The genetic test revealed something unusual: the patient had inherited a genetic variation that caused sitosterolemia, a rare disease where the body can’t properly eliminate plant sterols (fats found in plants). This is different from the more common familial hypercholesterolemia that doctors initially suspected. The genetic variation was particularly unusual because it came from a phenomenon called uniparental disomy, where the patient inherited two copies of a faulty gene from her father instead of one from each parent.
Once the diagnosis was confirmed, doctors changed the treatment approach. Instead of just lowering overall cholesterol, they restricted plant sterols in the diet and added a medication called ezetimibe, which blocks the absorption of these plant fats. The results were dramatic: within four months, the patient’s cholesterol levels normalized and her symptoms improved significantly.
This case is important because it demonstrates why genetic testing should be considered earlier for patients whose cholesterol doesn’t respond to standard treatments. Many patients with sitosterolemia are initially misdiagnosed with the more common familial hypercholesterolemia, delaying proper treatment by years. This case also represents the first documented instance of sitosterolemia caused by this specific genetic mechanism (uniparental disomy), expanding medical knowledge about how this rare disease can develop.
As a case report, this study documents one patient’s experience in detail rather than comparing multiple patients or groups. While case reports have limitations in proving general principles, they are valuable for identifying rare conditions and unusual presentations. The strength of this case lies in the use of modern genetic sequencing technology, which provided definitive identification of the underlying cause. The dramatic clinical improvement after targeted treatment supports the accuracy of the diagnosis. However, because this is one patient, the findings cannot be generalized to all patients with treatment-resistant cholesterol.
What the Results Show
The genetic sequencing identified a homozygous pathogenic variant in the ABCG5 gene caused by paternal segmental uniparental isodisomy of chromosome 2p. In simpler terms: the patient inherited two copies of a faulty gene from her father that prevents her body from properly handling plant sterols. This diagnosis explained why standard cholesterol medications weren’t working—the patient’s problem wasn’t excess cholesterol production, but rather inability to eliminate plant-based fats.
Following the diagnosis, treatment was changed to include dietary restriction of phytosterols (plant sterols) and the addition of ezetimibe medication. The results were remarkable: within four months, the patient’s LDL cholesterol (the “bad” cholesterol) normalized to healthy levels. This is particularly significant because the patient’s cholesterol had remained elevated despite 13 years of statin therapy and dietary restriction.
Clinically, the patient experienced marked improvement beyond just cholesterol numbers. She had been experiencing intermittent knee joint inflammation (periarthritis), which is a known complication of sitosterolemia. This symptom also improved with the new treatment approach. The patient’s xanthomas (fatty deposits under the skin that had developed at age two) also showed improvement.
The case highlighted the importance of considering rare genetic diseases in the differential diagnosis of treatment-resistant hyperlipidemia. The patient’s initial misdiagnosis with familial hypercholesterolemia delayed appropriate treatment by 13 years, during which time she experienced progressive symptoms including xanthomas and joint inflammation. The genetic mechanism identified—uniparental disomy—is an unusual inheritance pattern where both copies of a gene come from one parent rather than one from each parent. This was the first reported case of sitosterolemia caused by this specific genetic mechanism.
Sitosterolemia is a well-established but rare genetic disease, typically caused by mutations in either the ABCG5 or ABCG8 genes. However, this case represents the first documented instance of sitosterolemia caused by uniparental disomy of chromosome 2p. Previous cases of sitosterolemia have been caused by different types of genetic mutations. The dramatic response to targeted treatment (dietary phytosterol restriction plus ezetimibe) is consistent with the known pathophysiology of sitosterolemia and supports the accuracy of the diagnosis. This case also demonstrates that genetic testing should be considered earlier in patients with treatment-resistant hyperlipidemia, as previous literature has documented similar diagnostic delays in other sitosterolemia cases.
This is a single case report, so the findings apply specifically to this one patient and cannot be generalized to all patients with treatment-resistant cholesterol. The long-term outcomes beyond the four-month follow-up period are not documented. The case does not include information about whether the patient’s family members were screened for the same genetic condition. Additionally, as a retrospective case report, it documents what happened rather than testing a specific hypothesis through controlled research. The dramatic response to treatment in this case may not be representative of all sitosterolemia patients, as individual responses to treatment can vary.
The Bottom Line
If you have high cholesterol that doesn’t improve with standard medications (statins) and diet changes, especially if symptoms started in childhood or you have a family history of early heart disease, ask your doctor about genetic testing. Genetic testing may reveal rare conditions like sitosterolemia that require different treatment approaches. If sitosterolemia is diagnosed, dietary restriction of plant sterols combined with ezetimibe medication appears to be effective. These recommendations are based on this single case report, so discuss with your healthcare provider whether genetic testing is appropriate for your situation. (Confidence level: Low to Moderate—based on one case report rather than large clinical trials)
This case is most relevant to: (1) Young people with very high cholesterol that started in childhood, (2) Patients whose cholesterol doesn’t improve despite taking statins and following a low-cholesterol diet, (3) People with a strong family history of early heart disease, (4) Patients who have developed xanthomas (fatty bumps under the skin) or other complications of high cholesterol despite treatment. This case is less relevant to people with typical familial hypercholesterolemia or those whose cholesterol responds well to standard treatments. If you have treatment-resistant high cholesterol, discuss with your doctor whether you might benefit from genetic testing.
In this case, cholesterol levels normalized within four months of starting the targeted treatment (dietary phytosterol restriction and ezetimibe). However, individual responses may vary. Some patients may see improvements faster or slower. The xanthomas and joint symptoms also improved within this timeframe, but long-term follow-up data beyond four months are not provided in this case report.
Want to Apply This Research?
- If diagnosed with sitosterolemia, track daily dietary intake of plant sterols (found in nuts, seeds, vegetable oils, and whole grains) and log weekly LDL cholesterol readings if monitoring at home. Record any symptoms like joint pain or skin changes to monitor improvement over time
- Users with sitosterolemia can use the app to: (1) Log foods high in plant sterols to avoid or limit, (2) Set reminders for ezetimibe medication doses, (3) Track cholesterol levels from lab tests, (4) Monitor symptom improvement (joint pain, xanthomas), (5) Record doctor appointments and genetic counseling sessions
- Establish a baseline of current cholesterol levels and symptoms, then track weekly or monthly depending on treatment phase. After treatment changes, monitor more frequently (weekly) for the first 4 months to assess response, then transition to monthly or quarterly monitoring. Include both lab values and symptom tracking to get a complete picture of treatment effectiveness
This case report documents one patient’s experience and should not be considered medical advice. Sitosterolemia is a rare genetic disease, and most people with high cholesterol do not have this condition. If you have high cholesterol that doesn’t respond to standard treatments, consult with your healthcare provider or a genetic specialist to determine whether genetic testing is appropriate for you. Do not change your cholesterol medications or diet without guidance from your doctor. This article is for educational purposes only and does not replace professional medical diagnosis or treatment.