|Year : 2019 | Volume
| Issue : 1 | Page : 33-35
First report of coexistence of sickle cell disease and neurofibromatosis Type 1 in a Saudi patient with family history of neurofibromatosis Type 1
Nawaf Alanazi1, Ibrahim Almubarak2, Zainab Almoosa2, Zafar Iqbal3
1 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, National Guard Health Affairs; Department of Clinical Laboratory Sciences, King Abdulaziz Hospital; Department of Pediatrics, Hematology/Oncology Section, King Abdulaziz Medical City, National Guard Health Affairs, Al-Ahsa, Saudi Arabia
2 Department of Clinical Laboratory Sciences, King Abdulaziz Hospital, Al-Ahsa, Saudi Arabia
3 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences; Department of Pediatrics, Hematology/Oncology Section, King Abdulaziz Medical City, National Guard Health Affairs, Al-Ahsa, Saudi Arabia
|Date of Web Publication||30-Apr-2019|
College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences; King Abdulaziz Hospital, King Abdulaziz Medical City, National Guard Health Affairs, Al-Ahsa
Dr. Zafar Iqbal
College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Al-Ahsa
Source of Support: None, Conflict of Interest: None
Sickle cell disease is highly prevalent in Saudi Arabia, especially in the eastern and southern regions of the country. Neurofibromatosis Type 1 is one of the most common autosomal dominant disorders. In our case, we report a coexistence of both these diseases in a 15-year-old girl. This coexistence has never been reported in literature. Clinical manifestations of both the diseases and their possible link with each disease are discussed.
Keywords: Hemoglobinopathy, neurofibromatosis Type 1, sickle cell disease
|How to cite this article:|
Alanazi N, Almubarak I, Almoosa Z, Iqbal Z. First report of coexistence of sickle cell disease and neurofibromatosis Type 1 in a Saudi patient with family history of neurofibromatosis Type 1. J Appl Hematol 2019;10:33-5
|How to cite this URL:|
Alanazi N, Almubarak I, Almoosa Z, Iqbal Z. First report of coexistence of sickle cell disease and neurofibromatosis Type 1 in a Saudi patient with family history of neurofibromatosis Type 1. J Appl Hematol [serial online] 2019 [cited 2019 Jul 22];10:33-5. Available from: http://www.jahjournal.org/text.asp?2019/10/1/33/257472
| Introduction|| |
Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy characterized by single-base mutation of adenine to thymine, producing a substitution of valine for glutamic acid at the sixth codon of the beta globin chain. SCD is fairly common in Saudi Arabia with a prevalence of 2.6% in some areas. There are various clinical manifestations associated with SCD, affecting multiple body systems, with variable levels of severity in different parts of the world.
Neurofibromatosis Type 1 (NF1) is a genetic disorder inherited in an autosomal dominant pattern with a mutation in NF1 gene which codes for tumor suppressor gene neurofibromin, with an incidence of approximately 1 in 3000. Studies to assess the exact prevalence of NF in Saudi Arabia are still insufficient in Saudi Arabia, but in 2006, a study identified nine patients with NF among a total of 114 congenital cerebral malformations. NF1 is characterized by neurocutaneous signs, such as café au lait spots, axillary freckling, cutaneous neurofibromas, and iris hamartomas (Lisch nodules). NF1 is considered a multisystem disorder, with various manifestations affecting multiple systems including the eyes, musculoskeletal system, endocrine glands, blood vessels, as well as central nervous system (CNS). It affects multiple body systems including cutaneous system with café au lait spots, nervous CNS causing benign and sometimes malignant tumors and musculoskeletal systems. On the other hand, SCD has various ways of presentation and is associated with multiple complications; for example, a vaso-occlusive crisis for multiple systems including CNS and aplastic, sequestration, and hematolytic crisis.
This case report describes the presentation and diagnosis of the coexistence of two genetic disorders namely SCD and NF1 in the same patient. The presence of both SCD and NF1 has never been reported in literature.
| Case Report|| |
The present case was a 15-year-old female, a known case of SCD. Her parents are sickle cell traits, and two of her siblings are carriers as well. She is on hydroxyurea, folic acid, and prophylactic penicillin. Her vaccination schedule is up to date.
At the age of 3, she presented to a pediatrician with a painless left-sided facial swelling. She was referred to maxillofacial surgery for further evaluation and management. Examination of the face revealed isolated three lumps in the left cheek with a deviation of the left angle of the mouth and nose downwards. On palpation, those lumps were soft in consistency, nontender, nonfluctuant, and fixed to the deeper structure and were described as large plexiform neurofibroma. Examination of the skin revealed multiple café au lait spots all over the body, the largest being 3.0 cm × 5.0 cm in size [Figure 1]. No other positive neurological or systemic findings were described, and the patient's development was appropriate for age. Magnetic resonance imaging was done for the mass which revealed multiple tiny subcutaneously and intramuscularly enhancing nodules that are consistent with plexiform neurofibroma.
|Figure 1: Visible mass on the left side of the face along with multiple café au lait spots|
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Surgery was decided after referral to maxillofacial surgery, so the tumor masses were dissected, resected, and sent for biopsy. Total debulking of the mass was suggested and it was planned to wait until at the age of 17.
Furthermore, the patient was found to have left optic nerve glioma [Figure 2]. The patient was also diagnosed with mild right renal artery stenosis by a relatively mild increase in the left main renal artery peak systolic velocity. The combination of plexiform neurofibroma, café au lait spots, and optic glioma indicates the diagnosis of NF1. Interestingly, the patient's father and uncle described having café au lait spots.
|Figure 2: Magnetic resonance imaging findings: Multiple abnormal bright flair/T2 signals seen at both global pallidi, left crus cerebri, and both cerebellar white matter. Abnormal thickening of the left part of optic chiasm extending to the left prechiasmatic optic nerve with slight increase on postcontrast. Left infraorbital soft-tissue high T2 signal which enhances on postcontrast suggesting infraorbital neurofibroma. Findings suggesting Type 1 neurofibromatosis|
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Regarding SCD, hemoglobin (Hb) electrophoresis findings were HbS 80% and HbF 3. As she usually requires admission, she was admitted multiple times in a year (around five to six times per year) for vaso-occlusive crisis as a complication of her sickle cell anemia. She was admitted at the age of 10 years as a case of acute chest syndrome. At the age of 13, she was admitted as a case of bilateral osteomyelitis of the femur which was treated with ciprofloxacin. The patient was also diagnosed with mild right renal artery stenosis as detected by a relatively mild increase in the left main renal artery peak systolic velocity. The patient received transfusions once and sometimes twice yearly.
| Discussion|| |
NF1 is a common multisystem neurocutaneous condition. In order to diagnose NF1, it is required to have two or more of the well-known seven diagnostic criteria, [Table 1]. Three out of those criteria were present in our case, which are neurofibromas, café au lait spots, and optic nerve glioma. As NF1 has never been reported in literature in coexistence with SCD or other hemoglobinopathies, we tried to find a link or an association between those two genetic disorders.
|Table 1: Diagnostic criteria for neurofibromatosis 1 (NIH consensus development conference 1988)@|
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Our patient's main presentation was a facial mass due to plexiform neurofibroma. However, she could have this mass as a complication of SCD if she had extramedullary hemopoiesis. Hemopoiesis is the formation and maturation of blood elements. It normally occurs in the marrow of long bones, ribs, and vertebrae. In case of hemoglobinopathies, the primary sites of hemopoiesis fail, so extramedullary hematopoiesis happens in certain sites such as liver and spleen. It can involve any organ or tissue and manifest as a mass.
NF1 has an increased risk of developing different types of benign and malignant tumors affecting multiple systems including CNS, skin, gastrointestinal (GI) tract, and hematological malignancies. On the other hand, people with SCD may have an increased risk of developing similar malignancies found in NF1 like leukemia and solid tumors.
Patients with NF1 can suffer from other types of anemia. It can happen secondary to lower GI bleeding in case of GI tumors. Furthermore, one case developed autoimmune hemolytic anemia in association with NF1 in a 48-year-old female.
Based on the literature, both NF1 and SCD have vascular complications. SCD has a high risk of micro- and macro-vasculopathies including renal, pulmonary and cerebral complications, leg ulcers, and priapism, whereas NF1 can also be associated with similar vascular abnormalities, commonly affecting renal arteries, aorta, and mesenteric and cerebral arteries. In the case reported, the patient had renal artery stenosis which could have been caused by both sickle cell anemia (SCD) and NF1.
To conclude, although both conditions share few common manifestations, it is difficult to establish a clear link between NF1 and SCD and the effects of each condition on the other. Further clinical and molecular genetic studies are suggested to find a connection between NF1 and SCD and, if they add to the pathophysiology, severity or clinical outcome of each other.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]