Bone Marrow Failure Syndrome Type 1 (BMFS1)

Bone Marrow Failure Syndrome Type 1 (BMFS1) is a rare, autosomal-dominant inherited disorder where the bone marrow slowly stops making enough healthy blood cells. People can present in childhood with aplastic anemia (low red cells, white cells, and platelets) or later in adulthood with myelodysplastic syndrome (MDS). Some families also report ear problems such as deafness or labyrinthitis. The underlying genetic cause identified so far is damaging variants in SRP72, a component of the signal-recognition particle; this form was originally called “autosomal-dominant aplasia and myelodysplasia.” Over time, the failure of marrow cell production leads to tiredness (from anemia), easy bruising/bleeding (from thrombocytopenia), and infections (from neutropenia). Because malignant transformation can occur in marrow-failure syndromes, patients need close hematology follow-up and, when appropriate, early HSCT planning. PubMed+2NCBI+2

Bone Marrow Failure Syndrome type 1 (BMFS1) is a rare, inherited (runs in families) blood disease. In BMFS1, the soft tissue inside bones (the bone marrow) cannot make enough normal blood cells—red cells, white cells, and platelets. This shortage can start in childhood or later in adult life. Some people develop aplastic anemia (very low blood cell production). Others develop myelodysplastic syndrome (MDS) in adulthood (the marrow makes abnormal cells that do not work well). A few families also report ear problems such as hearing loss or labyrinthitis (inner ear inflammation). The condition is usually passed in an autosomal dominant way, meaning one changed gene from either parent can cause the disease. A key gene linked to BMFS1 is SRP72; harmful changes in SRP72 disturb normal protein targeting in cells, which can damage early blood-forming cells and lead to marrow failure. Molecular (genetic) testing confirms the diagnosis. Treatment depends on severity and may include supportive care, infection prevention, growth factors, and in severe cases, stem cell (bone marrow) transplant. PMC+3NCBI+3MalaCards+3

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Other names

• Bone marrow failure syndrome-1

• BMFS1

• Inherited bone marrow failure syndrome 1 (IBMFS1)

• Autosomal dominant aplasia/myelodysplasia (in some databases)
  These terms describe the same family-linked disorder with early aplastic anemia or adult-onset MDS, sometimes with ear problems. NCBI+1

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Types

BMFS1 shows a spectrum. You can think of “types” as common clinical patterns rather than totally separate diseases:

1. Childhood-onset aplastic anemia pattern – low blood counts across one or more cell lines beginning in youth. NCBI

2. Adult-onset MDS pattern – people stay well in youth but later develop MDS with cytopenias. NCBI

3. Hematologic-only pattern – only blood and marrow findings without other organ problems. Medscape

4. Hematologic + ear involvement pattern – marrow failure plus hearing loss or labyrinthitis in some families. NCBI

5. Mild (oligosymptomatic) pattern – intermittent low counts or mild anemia, discovered on routine tests. Medscape

6. Severe pancytopenia pattern – marked shortage of all three cell lines needing urgent care. NCBI

7. Progressive pattern – starts mild and slowly worsens to transfusion needs or MDS. Medscape

Note: These patterns reflect how the same genetic condition can look different in different people, even in one family. ASH Publications

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Causes

For BMFS1, the root cause is genetic. The list below explains the genetic driver and common contributors that can trigger, unmask, or worsen marrow failure in this syndrome.

1. Pathogenic variants in SRP72 (primary cause of IBMFS1/BMFS1). PMC

2. Autosomal dominant inheritance (one altered copy is enough). NCBI

3. Haploinsufficiency / dominant-negative effects of SRP72 that impair the signal recognition particle pathway and protein targeting, stressing progenitor cells. (Mechanistic framing from disease descriptions of SRP72-related IBMFS1.) PMC

4. Physiologic stressors (severe infections) that increase marrow demand and reveal limited reserve. NCBI

5. Certain medications (e.g., chemotherapy) can aggravate cytopenias in someone with inherited marrow fragility. NCBI

6. Viral infections (e.g., parvovirus B19) that suppress erythropoiesis and unmask failure. NCBI

7. Autoimmune activation that targets marrow, compounding inherited failure. NCBI

8. Nutritional deficits (B12/folate) worsening anemia in a vulnerable marrow. NCBI

9. Environmental toxins (benzene and others) adding additional marrow injury. NCBI

10. Chronic inflammation (elevated cytokines) that suppresses hematopoiesis. NCBI

11. Pregnancy-related demands occasionally unmask underlying IBMFS. Medscape

12. Endocrine issues (hypothyroidism can worsen anemia) superimposed on IBMFS. Cleveland Clinic

13. Clonal evolution (acquiring additional somatic mutations) leading toward MDS. Medscape

14. Telomere attrition with age stressing stem cell pools (general IBMFS concept). Blood Research

15. Oxidative stress in marrow microenvironment. NCBI

16. Bone marrow microenvironment defects that limit stem cell support. ScienceDirect

17. Coexisting immune disorders adding cytopenias. NCBI

18. Unrecognized congenital variants in other IBMFS genes that modify severity. PMC

19. Ageing of hematopoietic stem cells decreasing reserve over time. Medscape

20. Unknown/undetected genetic modifiers within a family (variable expressivity). ASH Publications

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Symptoms

People with BMFS1 may have none, some, or many of these symptoms. Symptoms often come from low blood counts.

1. Tiredness and weakness (from anemia). Cleveland Clinic

2. Pale skin (anemia). Cleveland Clinic

3. Shortness of breath with activity (low red cells). Cleveland Clinic

4. Dizziness or rapid heartbeat (anemia). Cleveland Clinic

5. Frequent or severe infections (low white cells). Cleveland Clinic

6. Fever during infections (neutropenia). NCBI

7. Mouth ulcers or sore throat that do not heal fast (neutropenia). NCBI

8. Easy bruising (low platelets). Cleveland Clinic

9. Nosebleeds or gum bleeding (thrombocytopenia). Cleveland Clinic

10. Tiny red skin spots (petechiae; low platelets). Cleveland Clinic

11. Prolonged bleeding from small cuts (low platelets). Cleveland Clinic

12. Unintended weight loss or poor appetite during long illness. NCBI

13. Night sweats with infections or clonal changes. Medscape

14. Hearing loss, ringing, or vertigo in families where ear problems occur. NCBI

15. Bone pain or fullness in the belly (rare; if spleen enlarges with MDS). Medscape

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Diagnostic tests

A) Physical examination

1. General exam and vital signs – looks for fever, pallor, fast heart rate, low blood pressure. Helps gauge urgency and infection risk. NCBI

2. Skin and mucosa check – finds bruises, petechiae, gum bleeding, mouth ulcers that suggest low platelets or neutropenia. Cleveland Clinic

3. Abdomen exam – checks spleen/liver size; enlargement may hint at MDS or infection. Medscape

4. Ear and neurologic screen – checks hearing and balance if inner-ear symptoms are present. NCBI

B) “Manual” bedside/office tests

5. Point-of-care hemoglobin – quick finger-stick estimate of anemia; prompts full labs. NCBI

6. Orthostatic blood pressure/heart rate – looks for dizziness and volume depletion in bleeding. NCBI

7. Bedside infection screen (temperature curve, oximetry) – identifies neutropenic sepsis risk. NCBI

8. Office hearing screening (whisper/tonal apps) – if abnormal, proceed to formal audiology. NCBI

C) Laboratory & pathological tests

9. Complete blood count (CBC) with differential – confirms low red cells, white cells, and/or platelets. Core test. Cleveland Clinic

10. Reticulocyte count – shows whether the marrow is trying to make new red cells; often low in marrow failure. NCBI

11. Peripheral blood smear – a doctor looks at cells under a microscope; can show abnormal shapes (dysplasia) suggesting MDS. Medscape

12. Bone marrow aspirate and biopsy – the key procedure: shows cellularity (too few cells in aplastic anemia) or dysplasia (MDS); allows cytogenetics. Medscape

13. Cytogenetics/karyotype & FISH – looks for chromosome changes seen in MDS or evolving clones. Medscape

14. Next-generation sequencing gene panel for IBMFS – detects SRP72 variants and screens other IBMFS genes; confirms inherited disease and guides family testing. Mayo Clinic Laboratories

15. Exclude mimics – tests for B12/folate, thyroid function, viral studies (parvovirus, hepatitis, HIV) and PNH flow cytometry, so treatable non-inherited causes are not missed. NCBI

16. Chromosome breakage test (DEB/MMC) – rules out Fanconi anemia, another inherited marrow failure. Cancer Epidemiology Division

17. Telomere length assay – helps exclude dyskeratosis congenita/telomere biology disorders when the picture is unclear. Blood Research

D) Electrodiagnostic / specialized physiologic tests

18. Formal audiology & ABR (auditory brainstem response) – documents sensorineural hearing loss in families with ear involvement. NCBI

19. ECG/echocardiogram if symptomatic – checks heart strain from severe anemia (shortness of breath, chest symptoms). Cleveland Clinic

E) Imaging tests

20. Ultrasound (spleen/liver) or CT only if indicated – looks for organ enlargement, infection complications, or pre-transplant evaluation; imaging is not always required for diagnosis but can support management. Medscape

Non-pharmacological treatments

1. Early Hematology care & family genetic counseling. Early specialist input confirms SRP72-BMF, screens relatives, and plans transplant. It reduces risky delays and helps avoid marrow-toxic drugs. NCBI+1

2. Infection-prevention bundle. Hand hygiene, dental care, food-safety, and prompt fever reporting (≥38 °C). Neutropenia turns “small infections” into emergencies; prevention cuts hospitalizations. NCBI

3. Fever action plan (24/7). Clear steps: check temperature, seek urgent care, blood cultures, broad-spectrum antibiotics. Time to antibiotics saves lives in neutropenia. NCBI

4. Transfusion support protocols. Leukoreduced, irradiated products lower alloimmunization and graft-versus-host risks pre-HSCT; careful thresholds limit iron loading. Medscape

5. Iron-overload monitoring & phlebotomy/chelation planning. Track ferritin and MRI-T2*; act early to protect heart/liver while awaiting HSCT. Medscape

6. Vaccination optimization. Follow inactivated vaccine schedules; household contacts get annual influenza and age-appropriate vaccines to create a cocoon. Live vaccines may be deferred in profound immunosuppression. Medscape

7. Nutrition optimization (B12, folate, copper). Deficits worsen cytopenias; dietician-guided repletion supports hematopoiesis. ods.od.nih.gov+1

8. Activity pacing & energy conservation. Structured rest, graded activity, and fall-prevention reduce bleeding risk and fatigue. NCBI

9. Oral care protocol. Soft brush, saline rinses, prompt ulcer care reduce bacteremia risk. NCBI

10. Catheter care education. If central lines are used, strict asepsis training prevents line sepsis. Medscape

11. Fertility counseling. Discuss HSCT/conditioning effects and fertility preservation when appropriate. Medscape

12. Hearing support. Audiology referral and assistive devices in families with ear involvement improve quality of life. NCBI

13. Psychosocial support. Chronic rare disease care benefits from counseling and peer support groups. Medscape

14. Sun-safe behavior. If on photosensitizing meds or with fragile counts, basic photoprotection is sensible. Medscape

15. Occupational/school planning. Infection-aware accommodations and reduced exposure during neutropenia periods. Medscape

16. Travel readiness. Carry medical summary, antibiotics plan, and transfusion history; avoid high-risk destinations during neutropenia. Medscape

17. Home temperature & bleeding logs. Structured self-monitoring prompts earlier, safer care. Medscape

18. Avoidance of marrow-toxic exposures. Solvents (benzene), unnecessary radiation, and certain drugs. Medscape

19. Dental prophylaxis coordination. Platelet thresholds and antibiotic plans for procedures reduce complications. Medscape

20. Early HSCT evaluation at an experienced center. Outcomes are better with timely referral before clonal evolution. NCBI

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Drug treatments

Important: None of the following medicines is approved to cure BMFS1. They are used to manage complications (infection risk, anemia, thrombocytopenia, iron overload) or to prepare for HSCT. Label citations below come from accessdata.fda.gov (FDA). Always individualize dosing with a hematologist.

1. Filgrastim (NEUPOGEN, G-CSF). Helps the marrow release neutrophils to prevent/treat febrile neutropenia or to mobilize cells. Typical oncology dosing is daily subcutaneous injections titrated to ANC; adverse effects include bone pain and rare splenic rupture. Useful short-term in severe neutropenia or peri-HSCT. FDA Access Data+1

2. Pegfilgrastim (NEULASTA). Long-acting G-CSF given as a single dose per chemotherapy cycle in oncology or for acute radiation syndrome; in inherited BMF it’s used selectively for prolonged neutropenia episodes. Side effects overlap filgrastim. FDA Access Data+1

3. Eltrombopag (PROMACTA). A thrombopoietin-receptor agonist approved for refractory severe aplastic anemia; it can raise platelets and sometimes other lineages. Dosing is oral and adjusted by platelet response; monitor for liver tests and risk of clonal evolution. Use with care in inherited BMF after expert review. FDA Access Data+2FDA Access Data+2

4. Romiplostim (NPLATE). Injectable TPO-RA (approved for ITP). Sometimes considered off-label to raise platelets; monitor for marrow fibrosis and thrombotic risks. FDA Access Data+2FDA Access Data+2

5. ATGAM (anti-thymocyte globulin, equine). Approved for moderate-to-severe aplastic anemia in patients not suitable for transplant. In inherited BMF, immunosuppression is often less effective than in acquired AA; decision requires expert genetics input. U.S. Food and Drug Administration+1

6. Deferasirox (JADENU/EXJADE). Oral iron chelator for transfusion-related iron overload; dose by weight and ferritin, and monitor renal/hepatic function. Reduces iron burden while awaiting or after HSCT. FDA Access Data+2FDA Access Data+2

7. Broad-spectrum antibiotics (e.g., levofloxacin) per neutropenic fever pathways. FDA-labeled antibiotics are used per culture/guideline; urgent empiric therapy is standard in fever with neutropenia. (Representative label anchors are available for individual agents.) Medscape

8. Antifungal prophylaxis/treatment (e.g., posaconazole) in prolonged neutropenia. Used per infectious-disease protocols to prevent invasive mold disease. (FDA labels anchor dosing/monitoring.) Medscape

9. Antiviral therapy (e.g., acyclovir) when indicated. For HSV/VZV prophylaxis or treatment in severely immunocompromised states. (FDA labels anchor dosing.) Medscape

10. Erythropoiesis-stimulating agents (epoetin alfa, darbepoetin alfa). Selected use for symptomatic anemia with low endogenous EPO; monitor thrombotic risk and iron status. (FDA labels anchor dosing.) Medscape

11. Folate supplementation (prescription strength) when low. Correcting deficiency can improve macrocytic anemia; avoid empiric folate if B12 status unknown. (FDA anchors for folic acid tablets.) ods.od.nih.gov

12. Vitamin B12 (cyanocobalamin). Oral or intramuscular replacement if deficient; prevents megaloblastic anemia and neuropathy. ods.od.nih.gov

13. Copper repletion (oral/IV) if deficient or if zinc-induced deficiency exists. Correcting copper can resolve anemia/neutropenia. PMC

14. Granulocyte transfusions (specialist use). In life-threatening infections with profound neutropenia unresponsive to G-CSF/antibiotics; logistics/risks require tertiary-center protocols. Medscape

15. Platelet transfusions. To treat/prevent bleeding; use leukoreduced/irradiated components and follow threshold-based protocols. Medscape

16. Red-cell transfusions. For symptomatic anemia; manage iron loading in parallel. Medscape

17. Conditioning agents for HSCT (e.g., busulfan, cyclophosphamide) per transplant protocol. Doses are individualized; FDA labels anchor safety/monitoring. Medscape

18. Plerixafor (mobilization) in specific settings. Used to mobilize stem cells in combination with G-CSF; transplant center decision. (FDA label anchors dosing.) Medscape

19. IVIG in selected immune complications or severe infections per specialist judgment. (FDA labeling anchors dosing and safety.) Medscape

20. Prophylactic antimicrobial regimens (fluoroquinolone/azole/HSV prophylaxis) during prolonged severe neutropenia per institutional guidelines anchored on labeled products. Medscape

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Dietary molecular supplements

1. Vitamin B12—cofactor for DNA synthesis; prevents megaloblastic anemia; oral or IM if low. ods.od.nih.gov

2. Folate—DNA base synthesis; deficiency worsens macrocytosis. ods.od.nih.gov

3. Copper—supports iron mobilization and hematopoiesis; replace if low. ods.od.nih.gov+1

4. Zinc (avoid excess)—supports immune cell maturation, but high doses reduce copper and can worsen cytopenias. ods.od.nih.gov+1

5. Vitamin D—bone/immune modulation; support general health pre-HSCT. (Use standard ODS guidance.) ods.od.nih.gov

6. Vitamin C—supports iron metabolism and immunity; food-first approach. ods.od.nih.gov

7. Protein (amino acids)—adequate intake supports marrow protein synthesis. ods.od.nih.gov

8. Omega-3 fatty acids—general anti-inflammatory support; avoid high doses with thrombocytopenia. ods.od.nih.gov

9. Iron—only if iron-deficient (most transfused patients have excess); check ferritin before supplementing. Medscape

10. Multivitamin without iron—reasonable safety net if diet is limited; avoid megadoses. ods.od.nih.gov

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Immune-booster / regenerative / stem-cell-related” drugs

These are not disease-modifying for SRP72 itself, but relevant around HSCT or immune support.

1. Filgrastim—boosts neutrophil production/mobilization; subcutaneous; monitor counts and bone pain. FDA Access Data

2. Pegfilgrastim—long-acting neutrophil support; single SC dose; similar cautions. FDA Access Data

3. Plerixafor—mobilizes stem cells for collection with G-CSF; dosing per label; watch for leukocytosis. Medscape

4. IVIG—broad immune support in selected scenarios (e.g., recurrent infections); dosing per product label. Medscape

5. Eltrombopag—stimulates megakaryocytes (and sometimes trilineage responses) in SAA; monitor LFTs and marrow. FDA Access Data

6. ATGAM—immunosuppression for aplastic anemia when HSCT not an option; in inherited BMF its role is limited; specialist decision. U.S. Food and Drug Administration

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Surgeries/procedures

1. Hematopoietic stem-cell transplantation (HSCT). The only curative approach for marrow failure; replaces faulty hematopoiesis with donor stem cells. For inherited BMF, many centers advocate timely HSCT before MDS/AML transformation. NCBI

2. Central venous catheter placement. Provides reliable access for transfusions, antibiotics, and chemotherapy/conditioning; meticulous line care prevents infection. Medscape

3. Bone-marrow biopsy/aspiration (diagnostic). Repeated as needed to track cellularity, dysplasia, and clonal evolution. Medscape

4. Splenectomy (rare, selected). Considered only for severe hypersplenism causing refractory cytopenias after exhaustive medical options; not routine. Medscape

5. Cochlear implant/ENT procedures (family-specific). For patients with significant sensorineural hearing loss associated with SRP72-BMF. NCBI

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Preventions

1. Avoid marrow-toxic drugs/solvents; review new meds with hematology. Medscape

2. Prompt fever plan and early antibiotics in neutropenia. NCBI

3. Vaccination updates for patient and household. Medscape

4. Food-safety and good oral hygiene to prevent infections. NCBI

5. Monitor ferritin and MRI-T2*; manage iron loading early. Medscape

6. Nutrition sufficiency (B12/folate/copper adequate, no megadoses of zinc). ods.od.nih.gov+2ods.od.nih.gov+2

7. Fall-prevention and bleed risk counseling with low platelets. NCBI

8. Early HSCT referral to reduce risk of clonal progression. NCBI

9. Scheduled hearing checks in families with ear involvement. NCBI

10. Regular specialist follow-up with CBC and marrow assessments. Medscape

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When to see a doctor

Seek urgent care for fever ≥38 °C, rigors, shortness of breath, chest pain, black stools, unusual bruising, severe headaches, or any rapidly worsening symptoms—especially if your white cells or platelets are low. Report new dizziness, fainting, or bleeding gums the same day. In BMFS1, prompt assessment prevents small issues from spiraling. NCBI

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What to eat (and avoid)

Eat: a varied diet with lean proteins (supports marrow protein synthesis), beans/lentils/leafy greens (folate), eggs/fish/dairy or fortified foods (B12), nuts/legumes/whole grains (copper and zinc in balanced amounts), fruits/vegetables, and plenty of fluids. This supports immune function and recovery during and after infections/transfusions. ods.od.nih.gov+1

Avoid: fad megadoses of single minerals (especially high-dose zinc, which can cause copper deficiency and worsen anemia/neutropenia), unpasteurized or undercooked foods during neutropenia, and alcohol excess that suppresses marrow. Always check supplements with your hematologist before starting them. ods.od.nih.gov

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FAQs

1) Is BMFS1 the same as Fanconi anemia? No. BMFS1 is SRP72-linked and autosomal-dominant; Fanconi anemia is usually autosomal-recessive and has different DNA-repair gene defects. Clinical issues overlap (cytopenias), but genetics and some management choices differ. NCBI+1

2) Is there a medicine that cures BMFS1? No specific drug cures the SRP72 defect. HSCT is the definitive therapy when indicated. NCBI

3) Does immunosuppression (ATG/cyclosporine) help inherited BMF? It can help acquired aplastic anemia and refractory SAA, but in inherited BMF its benefit is limited; use only after genetic evaluation. U.S. Food and Drug Administration

4) Can eltrombopag be used? It’s FDA-approved for refractory severe aplastic anemia and sometimes used to raise counts, but careful monitoring is needed in inherited BMF. FDA Access Data

5) Will I always need transfusions? Not always. Some patients need intermittent support; iron chelation prevents organ damage if transfusions are frequent. FDA Access Data

6) How often do I need labs? Your hematologist sets a cadence (often every 1–3 months, more often if counts are low or changing). Medscape

7) Can BMFS1 lead to leukemia/MDS? Yes—some patients present with or progress to MDS; that’s one reason why timely HSCT is discussed. NCBI

8) Should my family be tested? Yes. Because BMFS1 is autosomal-dominant, first-degree relatives may benefit from targeted testing and counseling. Mayo Clinic Laboratories

9) Can I exercise? Yes—light to moderate activity is encouraged, adjusted for fatigue and platelet count (avoid contact sports with thrombocytopenia). Medscape

10) Are vaccines safe? Inactivated vaccines are encouraged; timing of live vaccines depends on immune status and treatments. Medscape

11) What if I need dental work? Coordinate with hematology for platelet thresholds and antibiotic plans. Medscape

12) Does zinc help immunity? Adequate zinc supports immunity, but excess zinc can cause copper deficiency and worsen blood counts—don’t megadose. ods.od.nih.gov

13) Is pregnancy possible? Many patients can pursue pregnancy, but preconception counseling is important due to anemia/platelet/infection risks. Medscape

14) What about hearing problems? Some families with BMFS1 report ear issues; early audiology referral helps. NCBI

15) What’s the most important step? Establish care at an inherited bone-marrow-failure program and discuss transplant timing. Mayo Clinic Laboratories

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 30, 2025.

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