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PubMed This is a summary of 10 peer-reviewed journal articles Updated
Pediatric Hematology · SAMD9L-associated autoinflammatory disease

Symptoms, Warning Signs, and Emergency Care

At a Glance

SAMD9L-associated autoinflammatory disease can cause fever and rash, but fever may also reflect infection rather than sterile inflammation. Follow the child’s written plan, and seek emergency care for breathing trouble, seizures, sudden weakness, major bleeding, or fever with very low neutrophils.

Monitoring your child for symptoms of SAMD9L-associated autoinflammatory disease (SAAD) means watching for both “quiet” changes in coordination and “loud” signs of systemic inflammation. Because this condition can involve the immune system, the brain, and the blood, symptoms can appear in several different areas of the body, though neurologic findings are primarily associated with the ATXPC phenotype [1].

Skin and Systemic Inflammation

In SAAD, the body’s immune system can trigger intense inflammation even when there is no infection. This is known as sterile inflammation [2].

  • Panniculitis: This is one of the most common signs. It involves painful, red, or tender bumps under the skin caused by inflammation of the fat layer [2][3].
  • Pustular Rash: Especially in infants, a diffuse rash that looks like small, pus-filled blisters (pustules) may appear across the body [4].
  • High Inflammatory Markers: During a flare, blood tests often show very high levels of inflammatory markers (like CRP) and a high neutrophil (a type of white blood cell) count [2][4].
  • Persistent Fevers: Children may experience high fevers. Importantly, sterile inflammation and dangerous infections can coexist, and a lack of improvement on antibiotics cannot reliably distinguish them. Families must never assume a fever is merely sterile inflammation. Always follow an individualized urgent-evaluation plan [4].

Neurologic and Physical Coordination

Symptoms affecting the brain and nerves are part of the Ataxia-Pancytopenia (ATXPC) pattern on the SAMD9L spectrum, and new neurologic changes warrant assessment but are not universal features of SAAD [5][1].

  • Ataxia: This refers to a loss of coordination. You might notice your child becoming clumsy, having trouble walking in a straight line, or struggling with fine motor tasks like picking up small toys [5].
  • Nystagmus: This is an involuntary, rhythmic “shaking” or “jerking” of the eyes. It may be more noticeable when your child looks to the side [6].
  • Developmental Regression: Some children may lose physical milestones they had previously reached, such as the ability to sit up or crawl steadily [7].

When to Seek Care

It is important to understand that most daily symptoms—like a mild coordination issue or a stable skin bump—are “yellow flags” that you should discuss with your specialist during office hours. However, because SAAD can affect blood counts and the immune system, certain situations require faster action.

Red Flags: Emergency Care (Call 911 or Go to the ER)

The following symptoms represent a medical emergency, particularly in infants and young children [4][8]:

  • Difficulty Breathing: Grunting sounds, nostrils flaring, or the skin pulling in around the ribs or neck with every breath (retractions) [4].
  • Signs of Shock: A child who is extremely pale, blue, or gray; has very cold hands and feet; or is unusually floppy and difficult to wake up [4].
  • Neutropenic Fever: The true urgency of any new fever depends on your child’s Absolute Neutrophil Count (ANC), overall immune status, and the team’s specific fever protocol. However, if your child is known to have a very low white blood cell count (neutropenia), any fever (usually 100.4°F / 38°C or higher) must be treated as an emergency. In these cases, a simple infection can turn into life-threatening sepsis very quickly [9][10].
  • Major Bleeding: Uncontrolled bleeding from the nose or mouth, or a large amount of blood in the stool or urine. Furthermore, if your child has severe thrombocytopenia (low platelets), a sudden head injury or severe headache is a major emergency [8].
  • Sudden Neurologic Events: A sudden new weakness, altered awareness, or seizure requires immediate emergency evaluation.

Urgent: Same-Day Specialist Contact

Contact your child’s hematology or immunology team immediately if you notice:

  • Rapidly Spreading Rash: A pustular rash or painful skin lumps that are spreading quickly across the body [4].
  • New Neurologic Changes: A sudden, noticeable change in balance, new eye shaking, or a new weakness in the arms or legs [5].
  • Infection Signs: Any new fever, even if the child seems “okay,” as their immune system may not have enough B cells to fight off common germs [2][1].
  • Dehydration: Poor feeding, repeated vomiting, or significantly fewer wet diapers than usual [4].

Non-Emergency Symptoms

Stable and non-painful skin spots or a long-standing (baseline) coordination issue do not usually require emergency care. However, minor bruises or petechiae (pinpoint red spots) MUST be evaluated in the context of the child’s platelet count, and may require urgent care depending on the care team’s guidelines. These should be tracked and discussed at your next scheduled appointment. Always follow the specific “fever plan” provided by your child’s doctor.

Common questions in this guide

What symptoms can SAMD9L-associated autoinflammatory disease cause?
SAAD may cause sterile inflammation, painful lumps under the skin, pustular rashes, persistent fever, and abnormal blood counts. Children with the ATXPC pattern may also have loss of coordination, involuntary eye movements, or developmental regression, but neurologic symptoms are not present in every child.
When should a child with SAAD go to the emergency room?
Seek emergency care for breathing difficulty, blue, gray, or extremely pale skin, cold extremities with unusual floppiness or difficulty waking, uncontrolled bleeding, a seizure, sudden weakness, or altered awareness. If your child has known neutropenia, a fever at or above the threshold in the team’s plan—often 100.4°F (38°C)—is an emergency because infection can progress quickly.
Can a fever in a child with SAAD be only sterile inflammation?
A fever may be caused by sterile inflammation, but infection and sterile inflammation can occur at the same time. A lack of improvement on antibiotics cannot reliably distinguish them, so follow your child’s individualized fever plan and contact the care team or seek emergency care as instructed.
What does neutropenic fever mean for a child with SAAD?
Neutropenic fever is a fever in a child whose neutrophil count is very low. Because the immune system may not control infection effectively, the care team may treat a temperature of 100.4°F (38°C) or higher as an emergency; follow the child’s written protocol.
When should I call the hematology or immunology team the same day?
Call immediately for a rapidly spreading pustular rash or painful skin lumps, new balance problems or eye shaking, any new fever, or signs of dehydration such as poor feeding, repeated vomiting, or fewer wet diapers. The team can tell you whether your child needs same-day assessment or emergency care.
Are stable skin spots or long-standing clumsiness an emergency?
Stable, nonpainful skin spots and a long-standing coordination issue usually can be discussed during office hours rather than treated as an emergency. Bruises or pinpoint red spots must be interpreted alongside the platelet count and the care team’s instructions because they may require urgent evaluation.

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References

References (10)
  1. 1

    Genetic and clinical spectrum of SAMD9 and SAMD9L syndromes: from variant interpretation to patient management.

    Sahoo SS, Erlacher M, Wlodarski MW

    Blood 2025; (145(5)):475-485 doi:10.1182/blood.2022017717.

    PMID: 39475954
  2. 2

    SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression.

    Russell AJ, Gray PE, Ziegler JB, et al.

    Proceedings of the National Academy of Sciences of the United States of America 2021; (118(34)) doi:10.1073/pnas.2110190118.

    PMID: 34417303
  3. 3

    Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.

    de Jesus AA, Hou Y, Brooks S, et al.

    The Journal of clinical investigation 2020; (130(4)):1669-1682.

    PMID: 31874111
  4. 4

    A diffuse, pustular eruption in a neonate: Recognizing SAMD9L-associated autoinflammatory disease (SAAD).

    Miller MM, Rowe G, O'Brien K, et al.

    Pediatric dermatology 2024; (41(1)):112-114 doi:10.1111/pde.15411.

    PMID: 37571861
  5. 5

    Assessing Long-Term Neurologic Outcomes in SAMD9L-Related Ataxia-Pancytopenia Syndrome.

    Zingariello CD, Chen DH, Raskind WH, et al.

    Movement disorders clinical practice 2024; (11(6)):728-733 doi:10.1002/mdc3.14038.

    PMID: 38594844
  6. 6

    Ataxia-pancytopenia syndrome with SAMD9L mutations.

    Gorcenco S, Komulainen-Ebrahim J, Nordborg K, et al.

    Neurology. Genetics 2017; (3(5)):e183 doi:10.1212/NXG.0000000000000183.

    PMID: 28852709
  7. 7

    Successful Haploidentical Bone Marrow Transplantation of an Infant With a Novel Mutation in SAMD9L Gene (Ataxia-Pancytopenia Syndrome).

    Alicea Marrero MM, Español M, Marrero-Rivera G, et al.

    Journal of pediatric hematology/oncology 2022; (44(7)):419-420 doi:10.1097/MPH.0000000000002537.

    PMID: 36054901
  8. 8

    [Advancing the development of hematology care units to enhance hematology‑specific critical care capacity].

    Fan SJ, Li HT, Zhang X

    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 2025; (46(11)):985-990 doi:10.3760/cma.j.cn121090-20250922-00432.

    PMID: 41407454
  9. 9

    Acute cholecystitis in neutropenic patients.

    Clemente-Gutiérrez U, Sánchez Morales GE, Moctezuma Velazquez P, et al.

    Annals of hepato-biliary-pancreatic surgery 2019; (23(3)):234-239 doi:10.14701/ahbps.2019.23.3.234.

    PMID: 31501811
  10. 10

    Spontaneous remission and loss of monosomy 7: a window of opportunity for young children with SAMD9L syndrome.

    Erlacher M, Andresen F, Sukova M, et al.

    Haematologica 2024; (109(2)):422-430 doi:10.3324/haematol.2023.283591.

    PMID: 37584291

This page is for informational purposes only and does not constitute medical advice. It cannot replace your child’s individualized fever and emergency plan from their hematology, immunology, or other care team.

Guide contents SAMD9L-associated autoinflammatory syndrome
Research & Literature
01 Understanding SAMD9L-Associated Autoinflammatory Disease (SAAD) 03 The Biology of SAMD9L