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Life with DBA

This article discusses the pros and cons of treatment options for Diamond-Blackfan Anemia (DBA), a rare bone marrow failure disorder. It explores the impact of iron overload on various organs and the potential for endocrine dysfunction. The article also highlights the importance of timely diagnosis and treatment in preventing long-term adverse effects.

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Life with DBA

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  1. Life with DBA Adrianna Vlachos, MD The Feinstein Institute for Medical Research Hofstra North Shore-LIJ School of Medicine Cohen Children’s Medical Center of New York

  2. Pros and cons of DBA treatments

  3. Lessons from thalassemia

  4. Accumulation of iron • Liver • Endocrine glands • Heart • Often this is stepwise in thalassemia major • NOT so in DBA – Why?? Skin Usual progression of Iron overload

  5. Eventual fibrosis and organ failure • Heart: cardiomyopathy, conduction disturbances arrhythmia • Liver: abdominal pain, elevated LFTs, hepatomegaly fibrosis and cirrhosis • Skin: bronzing and gray pigmentation • Endocrine dysfunction Iron overload

  6. Liver with iron overload Normal liver

  7. Iron stain of liver – iron staining in hepatocytes and histiocytes

  8. Trichrome stain of liver – medium magnification to show liver cirrhosis with fibrosis and nodules in a patient with hepatic iron overload (no iron stain)

  9. Dilated cardiomyopathy with iron overload Hypertrophic cardiomyopathy

  10. Iron stain of heart

  11. Pancreas with massive iron overload Normal pancreas

  12. 30-50% of patients have delayed or absent puberty due to iron overload • After myeloablative BMT: • Females - ovarian malfunction in ~100% • Males - testicular dysfunction in 0-40% • Screening for pituitary-hypothalamic axis (LH and FSH) and sex hormones (Testosterone or Estradiol) Hypogonadism

  13. Reproduction and Infertility • Genitalia: primary hypogonadism • Pituitary gland: gonadotropin insufficiency leading to secondary hypogonadism Hypogonadism

  14. DBAR Women’s study open to review • Menarche • Pregnancy • Menopause • Preliminary results • Delayed puberty • Early menopause • ? Infertility issues Menarche to Menopause

  15. Found in 2-20 % of patients with iron overload • After bone marrow transplant: common • Screening with • Thyroid stimulating hormone (TSH) • Total and free Thyroid hormone (T4) Hypothyroidism

  16. Symptoms may be missed because of their vague nature. • Dark color of non-sun-exposed areas • Extreme tiredness • Nausea, vomiting, abdominal pain, diarrhea, constipation • Patients on steroids: considered to have adrenal insufficiency • 8-45% of patients with iron overload can have biochemical adrenal insufficiency (often partial) • Screening with 8 AM cortisol level, plasma renin activity, aldosterone, androstenedione and DHEAS levels Adrenal insufficiency

  17. Both corticosteroid therapy and iron overload can lead to: ↓ in insulin secretion and ↓ in insulin sensitivity Diabetes mellitus

  18. 9-14% of patients with iron overload • ? % of patients on chronic corticosteroids • ? after bone marrow transplant • Screening with • fasting blood glucose • fructosamine level • HbA1c is not reliable while on transfusions!! • oral glucose tolerance test Diabetes mellitus

  19. Growth

  20. Anemia and ?DBA (RP gene) Absent/ Abnormal puberty Iron overload Short stature Hypothyroidism Low Growth hormone Growth Glucocorticoids Short stature in DBA is multifactorial.

  21. Short stature reported in ~30-50% of DBA patients • Effect on growth may be due to iron overload or steroids • Screening with regular growth monitoring for early detection and more specific testing to check for endocrine causes. Growth

  22. Hypogonadism Low Vitamin D & parathyroid gland failure Iron overload Osteoporosis Diabetes mellitus ? Low Growth hormone Bone disorders Glucocorticoids Osteoporosis is multifactorial in DBA patients.

  23. No data yet on bone disorders for DBA patients • With iron overload: ??? • On chronic corticosteroids: ???? • After bone marrow transplant: ??? • Screening of calcium, parathyroid hormone, vitamin D and for other endocrine problems • Perform densitometry or DEXA scan Bone disorders

  24. Insulin resistance. Decreased insulin secretion. Impaired glucose tolerance. Years 12.4% ~10 Years Insulin dependent diabetes mellitus Insulin resistance. High insulin level. Normal glucose tolerance Intensive chelation in patients with impaired glucose tolerance can improve beta-cell function and improve blood glucose values. Less effective in patients who have developed DM and in improving insulin resistance. Importance of Chelation

  25. Timely diagnosis & treatment can prevent morbidity and possible mortality associated with some endocrine conditions. • If not, will develop long-term adverse effects of an undiagnosed/ untreated endocrine problem. Treatment for endocrinopathies

  26. *Unpublished data presented at Pediatric Endocrine society meeting at Washington DC, 2013

  27. SPECIFIC AIMS: • To study the effects of iron overload on the endocrine system in DBA patients receiving transfusions. • To estimate how common endocrinopathies are in the DBA population and correlate them with measures of iron overload. • To compare the presence of endocrine dysfunction in the chronic transfusion-dependent DBA population with those not on chronic transfusions. Endocrine research in DBAwith Drs. Lahoti, Speiser, and Harris

  28. Inclusion criteria: • Age 1-39 years; and • Diagnosed with DBA and enrolled in DBAR Exclusion criteria: • Pregnant; or • Have received a bone marrow transplant Eligibility Criteria

  29. Goal: • 50 transfusion dependent DBA • 25 steroid dependent and remission DBA • Completed and report to follow DBAR Research Study

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