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Year : 2020  |  Volume : 9  |  Issue : 1  |  Page : 45-47

A rare case report of coexistent neurofibromatosis type 1 with sickle cell beta-plus thalassaemia

Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India

Date of Submission17-Jan-2019
Date of Decision12-Apr-2019
Date of Acceptance07-Nov-2019
Date of Web Publication2-Jun-2020

Correspondence Address:
Naval Chandra
Additional Professor, Department of General Medicine, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500 082, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JCSR.JCSR_16_19

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A 28-year-old male presented with fever with chills, jaundice, body pains and dyspnoea for 3 days. There was a history of recurrent jaundice in the past. Physical examination revealed massive hepatosplenomegaly, and hence, thought of haemolytic anaemia and haemoglobin electrophoresis was done which is suggestive of sickle cell-beta-thalassaemia. He also has café-au-lait spots, inguinal freckling, neurofibromas and lisch nodules all suggestive of neurofibromatosis type 1 (NF1). He was evaluated for fever and found to have an abnormality on computed tomography chest suggestive of pulmonary tuberculosis (TB). The patient was treated with anti-TB therapy. We report the case because of the rare occurrence of NF1 with sickle cell-beta-thalassaemia, after screening the literature available till now. This case also highlights the fact that haemolytic anaemia patients may have pre-existing jaundice, and hence, antitubercular therapy should be given with caution to prevent hepatotoxicity.

Keywords: Neurofibromatosis type 1, neurofibromatosis with sickle cell anaemia, sickle cell-beta-thalassaemia

How to cite this article:
Vanka PK, Tejavath R, Chandra N, Swaroopa D, S. Subbalaxmi M V, Yedla DR. A rare case report of coexistent neurofibromatosis type 1 with sickle cell beta-plus thalassaemia. J Clin Sci Res 2020;9:45-7

How to cite this URL:
Vanka PK, Tejavath R, Chandra N, Swaroopa D, S. Subbalaxmi M V, Yedla DR. A rare case report of coexistent neurofibromatosis type 1 with sickle cell beta-plus thalassaemia. J Clin Sci Res [serial online] 2020 [cited 2020 Aug 15];9:45-7. Available from: http://www.jcsr.co.in/text.asp?2020/9/1/45/285709

  Introduction Top

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous multisystem disorder with autosomal dominant inheritance due to mutation of NF1 gene which encodes neurofibromin.[1] Sickle cell-beta-thalassaemia is an autosomal recessive condition, which results from the coinheritance of a sickle cell gene and a beta-thalassaemia gene. The clinical phenotype depends on the type of beta-thalassaemia gene (beta [+] or beta [0]) inherited.[2] Co-existence of NF1with sickle beta thalassaemia in the same patient was not reported previously as per our knowledge, and hence, we report this case.

  Case Report Top

A 28-year-old male, farmer from a tribal area, presented with chief complaints of fever with chills, generalised body pains, yellowish discolouration of eyes and shortness of breath for 3 days. The patient had similar episodes of body pains for 5 years of age. A history of recurrent jaundice since childhood relieved with herbal medication. There were no previous blood transfusions. No family history of haemolytic anaemias or recurrent blood transfusions was noted. His elder brother had multiple skin neurofibromas. Parents had no similar skin lesions as per the patient. The patient had sputum-positive pulmonary tuberculosis (TB), 18 months ago, treated with anti-tubercular drugs for 6 months. He takes alcohol (toddy) for the past 7 years which accounts to 60 g of ethanol per week. He is a product of third-degree consanguineous marriage. On examination, he was moderately built and ill-nourished with body mass index of 17.5 kg/m2. Pallor and icterus were present. No cyanosis, clubbing, lymphadenopathy and pedal oedema were noted. He had multiple cafe-au-lait spots, multiple cutaneous neurofibromas and inguinal freckling, as shown in [Figure 1]. The slit-lamp examination showed lisch nodules in the iris. Vitals were stable with a pulse rate of 92 bpm and blood pressure of 110/70 mm Hg. On respiratory system examination, bronchial breathing was present along with crepitations in left infra clavicular area. Per abdomen revealed non-tender, firm, massive hepatosplenomegaly with liver and spleen palpable 7 cm and 10 cm below the right and left subcostal margins. Neurological examinations revealed no neurological deficits. Cardiovascular examination was normal except for flow murmurs. On investigation, haemogram showed microcytic anaemia with haemoglobin (Hb) of 6.5 g/dL, total leucocyte count of 8500 cells/mm3 and platelet count of 90,000/mm3. Liver function tests showed total bilirubin is 7.0 (conjugated bilirubin 1 mg/dL). Renal function tests, blood glucose and serum electrolytes were normal. Serum lactate dehydrogenase was elevated. In view of haemolysis, haemoglobin electrophoresis was done in the biochemistry department of our institute which was suggestive of “sickle cell beta-plus thalassaemia” (haemoglobin S [HbS] 63%; haemoglobin A2 5.2%; haemoglobin F 21.8%; and haemoglobin A [HbA] = 9.3%). Chest X-ray showed a left upper zone opacity which was confirmed. Mutation analysis and haemoglobin electrophoresis for family members was planned but could not be done in view of financial constraints. Contrast-enhanced computed tomography (CECT) of the chest showed fibrosis with traction bronchiectasis in apico-posterior segment of the left upper lobe, lingular and right middle lobe and thin cavitatory lesion in the superior segment of the left upper lobe – suggestive of reactivation of pulmonary TB [Figure 2]. CECT of the abdomen showed massive hepatosplenomegaly with coarse calcifications in the spleen and gall bladder stones [Figure 3]. As the patient was not having cough, induced sputum was tested for acid-fast bacilli with auramine–rhodamine staining, Xpert MTB/RIF® testing and mycobacterial culture; all tested negative. Active TB was diagnosed based on history, clinical and radiological findings. A final diagnosis of NF1, sickle cell beta-plus thalassaemia with hypersplenism and pulmonary TB was made.
Figure 1: Clinical photograph showing café au lait spots over the thigh (a), multiple neurofibromas over abdomen (b); jaundice (c); and inguinal freckling (yellow arrow) (d)

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Figure 2: Contrast-enhanced computed tomography of the chest showing fibrosis with traction bronchiectasis in the apico-posterior segment of the left upper lobe and thin cavitatory lesion in the superior segment of the left upper lobe

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Figure 3: Contrast-enhanced computed tomography of the abdomen showing massive hepatosplenomegaly with coarse calcifications in the spleen and multiple gall bladder stones

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The patient improved with adequate hydration, blood transfusions as needed and other supportive measures. In view of deranged base-line liver functions, the patient was treated initially with modified anti-TB treatment with non-hepatotoxic drugs, ethambutol, levofloxacin and streptomycin for 13 days. After normalisation of liver functions, isoniazid and rifampicin were added sequentially in escalating dosage as per the British Thoracic Society guidelines,[3] which the patient tolerated. Pyrazinamide was not reintroduced. The patient showed gradual clinical improvement and was discharged on treatment with isoniazid, rifampicin, ethambutol and streptomycin. He continued taking the remaining course of anti-TB treatment at the DOT centre near his place of domicile.

  Discussion Top

Sickle cell disease and its variants are genetic disorders result from the presence of mutated haemoglobin, HbS. It is an autosomal recessive disorder. The association of β-thalassemia with sickle cell haemoglobin is reported in up to 1.7%.[4],[5]

Sickle cell disease can also result from the inheritance of β S in combination with a wide range of other haemoglobin B mutations, the two most common being a second structural β-globin variant β C and one of many β-thalassaemia mutations that lead to the decreased production of normal β-globin.[2] The haemoglobin B gene is located on chromosome number 11.

Sickle cell-beta thalassaemia is divided into sickle cell-beta zero thalassaemia and sickle cell beta-plus-thalassaemia, based on the complete absence of beta-globin or the presence of reduced amounts of beta-globin, respectively which in turn determines the level of HbA.[2] Our patient had sickle cell-beta-plus thalassaemia. The percentage of HbA produced in individuals with beta-plus thalassaemia ranges from 5% to 30%, depending on the molecular defect of the mutation. The clinical and haematologic severity of sickle cell-beta thalassaemia is an inverse function of HbA quantity.[6] Patients with sickle cell-beta zero thalassaemia (i.e., no HbA production) have a clinical course as severe as homozygous SCD; i.e., HbSS, sickle cell anaemia.[6] NF1 is an autosomal dominant neurocutaneous syndrome and has a prevalence of 1/3500 live births, thus being the most common autosomal dominant condition in humans.[1] It is due to mutations in NF1 gene located on chromosome number 17. It is characterised by the presence of multiple cafe-au-lait spots, cutaneous neurofibromas, inguinal or axillary freckling, lisch nodules, optic nerve gliomas, bony defects and family history of neurofibromatosis.[1] The presence of at least 2 of the 7 aforementioned clinical criteria is required for the diagnosis. Our patient fulfilled 5 of the 7 clinical criteria required for the diagnosis of NF1. We could not do genetic analysis for this patient in view of financial constraints. As per our knowledge, coexistence of NF1 with sickle cell beta-plus thalassaemia in the same patient has seldom been reported previously, and hence, we are reporting this case. This case is also unique in that this is an example for rare coexistence of both autosomal dominant and recessive conditions in the same patient. This case also highlights the importance of treating TB in the situation of existing baseline liver dysfunction.


The authors would like to thank the Departments of Pathology and Radiodiagnosis, Nizam's Institute of Medical Sciences, Hyderabad.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Boyd KP, Korf BR, Theos A. Neurofibromatosis type 1. J Am Acad Dermatol 2009;61:1-4.  Back to cited text no. 1
Vincent O, Oluwaseyi B, James B, Saidat L. Coinheritance of B-Thalassemia and Sickle Cell Anaemia in South Western Nigeria. Ethiop J Health Sci 2016;26:517-22.  Back to cited text no. 2
Chemotherapy and management of tuberculosis in the United Kingdom: Recommendations 1998. Joint Tuberculosis Committee of the British Thoracic Society. Thorax 1998;53:536-48.  Back to cited text no. 3
Balgir RS. Spectrum of hemoglobinopathies in the state of Orissa, India: A ten years cohort study. J Assoc Physicians India 2005;53:1021-6.  Back to cited text no. 4
Chakravorty S, Williams TN. Sickle cell disease: A neglected chronic disease of increasing global health importance. Arch Dis Child 2015;100:48-53.  Back to cited text no. 5
Serjeant GR, Sommereux AM, Stevenson M, Mason K, Serjeant BE. Comparison of sickle cell-beta0 thalassaemia with homozygous sickle cell disease. Br J Haematol 1979;41:83-93.  Back to cited text no. 6


  [Figure 1], [Figure 2], [Figure 3]


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