"SAMD9 Deficiency" – What Is It?
SAMD9 deficiency is a disease caused by mutations, i.e., genetic changes in the SAMD9 gene. It is also known as MIRAGE syndrome, an acronym made up of the most frequently observed symptoms: Myelodysplasia(disease of the bone marrow), infection, restriction of growth, adrenal hypoplasia (underdevelopment of the adrenal glands), genital abnormalities and enteropathy (disease of the intestines). In addition, numerous other abnormalities can occur in various organs. The disease is often fatal within the first ten years of life, usually due to severe infections.
How Is "SAMD9 Deficiency" Diagnosed?
Genetic Diagnostics
The “SAMD9 deficiency” diagnosis is confirmed by detecting a mutation, i.e., a genetic change in the SAMD9 gene.
What Is the Risk of Cancer?
The malignant neoplasm known to occur in SAMD9 deficiency is myelodysplastic syndrome (MDS), a rarer manifestation of SAMD9 deficiency. However, exactly how high the risk of developing MDS is is not yet known.
In addition, SAMD9 deficiency can lead to other diseases in various organ systems.
Bone Marrow Insufficiency or “Myelodysplasia”
A disease of the bone marrow associated with a defective production of blood cells is one of the leading manifestations. This can lead to thrombocytopenia (lack of platelets) and/or anemia (lack of red blood cells), which usually occurs in infancy but resolves spontaneously. Mild lymphopenia (lack of specific immune cells) may also occur, and some patients develop leukopenia (lack of white blood cells).
Infections
Almost all patients diagnosed to date have developed severe, sometimes recurring infections, often in the form of blood poisoning, meningitis, or severe fungal infections. Recurrent viral or bacterial infections can also occur. Severe infections are usually fatal before the child reaches the age of two.
Delayed Growth
Patients with the SAMD9 mutation are characterized by reduced longitudinal growth and low body weight, both before and after birth. Some patients also have intellectual and/or motor developmental delays.
Adrenal Hypoplasia
The underdevelopment of the adrenal glands (adrenal hypoplasia), frequently described in the context of a SAMD9 mutation, is usually characterized by increased skin pigmentation. This can be followed by signs of salt loss with vomiting, weight loss, and even clouding of consciousness, which are caused by hormonal disorders in the adrenal glands. Adrenal hypoplasia has been found in all patients who have been examined by ultrasound to date.
Genital Anomalies
Genetically male patients showed genital underdevelopment in the form of a very small penis, testicles localized in the abdomen, an incorrectly opening urethra, and even an entirely female external genitalia. Genetically female patients may have malformed ovaries. The ovaries may also be completely absent.
Enteropathy
A disease of the intestine manifests itself in the context of a SAMD9 mutation through chronic diarrhea and a widening of the large intestine. There may also be reflux of stomach contents into the esophagus.
Furthermore, an open ductus arteriosus in the heart, an underdeveloped or absent thymus, recurrent urinary tract infections, and skeletal anomalies (scoliosis, club hand, overlapping fingers, club feet, congenital flat feet) have been described.
SAMD9 Deficiency – What You Can Do Yourself
SAMD9 deficiency is caused by a mutation, i.e., a genetic change in the SAMD9 gene. This gene codes for the protein SAMD9, which acts as a growth repressor, i.e., inhibiting the proliferation of cells in our body. If the SAMD9 gene is present in an altered form, the protein’s activity increases, i.e., it strongly inhibits cell growth, which can lead to diseases with maldevelopment or underdevelopment of various organs.
Most cases known to date are new, so-called de novo mutations. In addition, autosomal dominant inheritance has been described.
What Is the Risk of Cancer?
Treating patients with SAMD9 deficiency requires a multidisciplinary approach involving physicians from pediatrics, hematology/oncology, infectious disease, endocrinology, genetics, and potentially other specialties. The therapy should be customized to address each patient’s specific manifestations.
In impaired hematopoiesis, a discussion with the EWOG-MDS study management is advisable. A bone marrow transplant may be an option for patients with MDS.
Diagnosis of " SAMD9 Deficiency" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " SAMD9 Deficiency" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
As SAMD9 deficiency is a sporadic disease, there is insufficient data to make standardized early detection recommendations.
As with other leukemia predisposition syndromes, the following examinations should be carried out regularly:
- Clinical examinations
- Annual complete blood count
- Bone marrow aspiration once initially and then in case of unstable blood values/clinical suspicion of MDS
- A bone marrow puncture once a year should be considered
SAMD9 Deficiency – What You Can Do Yourself
You Should Pay Attention to This
You should consult a doctor when you notice frequent infections, increased or difficult-to-stop bleeding (e.g., prolonged or frequent nosebleeds), increased bruising, fatigue, or a feeling of illness, fever, night sweats, or pallor. In addition, you should urgently consult a doctor if you experience increasing skin pigmentation, vomiting, weight loss, further gastrointestinal complaints, or clouding of consciousness. If other new symptoms or complaints occur, these should also be clarified as quickly as possible.
Further Information
Unfortunately, we are not yet aware of any support groups for patients with SAMD9 deficiency. As soon as we have new information, we will add it here. However, patients can also register for the CPS registry at any time or have this done by their doctors in charge.
Any further questions?
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