"SAMD9L Deficiency" – What Is It?
SAMD9L deficiency, also known as ataxia-pancytopenia syndrome, is caused by mutations, i.e., genetic changes, in the SAMD9L gene. It is characterized by cerebellar ataxia (a disorder of movement coordination due to damage in the cerebellum) and various forms of cytopenia (reduction of cells in the blood; can affect red or white blood cells or platelets). In addition, those affected have an increased risk of bone marrow failure, myelodysplastic syndrome (disease of the bone marrow), and acute myeloid leukemia (AML).
How Is "SAMD9L Deficiency" Diagnosed?
Suspected Diagnosis
The presence of SAMD9L deficiency is suspected in individuals who have more than one of the following findings:
- Cerebellar ataxia (a movement disorder caused by a malfunction of the cerebellum)
- Cytopenia of at least one cell line (e.g., anemia = lack of red blood cells, neutropenia = lack of white blood cells, thrombocytopenia = lack of platelets)
- Myeloid leukemia or myelodysplastic syndrome with monosomy 7 (genetic change in which chromosome 7 is only present once instead of twice as usual)
- Reduced cerebellar mass and changes in the white matter in the brain (visible on MRI)
- Occurrence of one of the above findings in the family
Genetic Diagnostics
The diagnosis of “SAMD9L deficiency” is confirmed by the detection of a mutation, i.e., a genetic change in the SAMD9L gene.
Clinical Diagnostics
To determine the extent of the disease, the following clinical diagnostics should be carried out after the genetic diagnosis has been made:
- Evaluation of the medical history
- Clinical examination including neurological examination
- MRI of the head
- Complete blood count
- Bone marrow puncture
What Is the Risk of Cancer?
The known malignant neoplasms associated with SAMD9L deficiency are myelodysplastic syndrome (MDS) and acute myeloid leukemia. The risk of developing one of these manifestations is not yet known. In addition, SAMD9L deficiency can lead to cytopenias, with anemia, i.e., a lack of red blood cells, being the most common form. The severity of cytopenia can vary from mild to very severe. The earliest onset of a disease of the hematopoietic system has been described as 3 months, but there is also great variability with regard to the age of manifestation.
Neurological diseases are another form of manifestation. To date, many patients with the SAMD9L mutation have been diagnosed with an abnormality of the nervous system. This is known as cerebellar ataxia, a disorder of movement coordination caused by damage to the cerebellum. Signs of this ataxia are gait and balance difficulties, rhythmic eye twitching (nystagmus), increased reflexes, and difficulties with pronunciation. The impaired gait and other neurological abnormalities are usually slowly progressive. The age of onset also ranges from infancy to 62 years. Neurological symptoms may also be absent.
What Is Known About the Development of "SAMD9L Deficiency" ?
SAMD9L deficiency is caused by a mutation, i.e., a genetic change in the SAMD9L gene. This gene codes for the SAMD9L protein, which acts as a tumor suppressor, i.e., controls the proliferation of cells in our body. If the SAMD9L gene is present in an altered form, the protein can no longer function correctly as a tumor suppressor, and neoplasms of the hematopoietic system develop.
SAMD9L deficiency can be passed on from parents to their children. The inheritance is autosomal dominant.
Is There Any Form of Treatment Available?
Treating patients with SAMD9L deficiency should be carried out in collaboration with physicians from various disciplines, such as pediatrics, hematology/oncology, neurology, and genetics. A discussion with the EWOG-MDS study management is advisable.
Manifestations of the Hematopoietic System
- Certain medications (e.g., ASA, ibuprofen, diclofenac) that impair blood clotting should be avoided in the case of thrombocytopenia (lack of platelets)
- Administration of appropriate blood products depending on the severity of the cytopenia
- Treatment of other causes of anemia, e.g., by taking iron or vitamins
- The treatment of myeloid neoplasia in patients with a SAMD9L mutation should be discussed with the relevant study center.
- Bone marrow transplantation may be an option, especially for patients with myeloid neoplasia.
Neurological Manifestations
The treatment of ataxia is purely supportive, as there is currently no therapy available that can slow or halt the progression of the disease.
- Alcohol and sedative medications should be avoided as they further impair gait and coordination.
- Patients should remain mobile for as long as possible. Walking aids can prevent falls.
- Weight control, as excess weight also restricts mobility
Diagnosis of " SAMD9L 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 " SAMD9L 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
The Following Examinations Should be Carried Out
- CBC annually, more frequently if blood count is unstable
- A bone marrow puncture once a year should be considered
- Education of the patient/family about symptoms that indicate cytopenia (e.g., tiredness, pallor, bleeding, recurrent infections)
- Annual clinical examination, especially about gait, coordination, and speech
SAMD9L Deficiency – What You Can Do Yourself
You Should Pay Attention to This
You should consult a doctor when you notice increased or difficult-to-stop bleeding (e.g., prolonged or frequent nosebleeds), increased bruising, fatigue, or a feeling of illness, fever, night sweats, paleness, or frequent infections. You should also consult a doctor if you notice any abnormalities in your gait, speech, eye twitching, or other movement or coordination difficulties. 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 SAMD9L 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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