|Year : 2017 | Volume
| Issue : 3 | Page : 110-113
A rare case of compound heterozygous B-thalassemia and hereditary persistence of fetal hemoglobin with Moya-Moya disease
Ashok Gupta1, Priyanshu Mathur2, Manish Sharma3, Vimesh Parmar4
1 Professor and Unit head, Department of Pediatrics, Department of Pediatrics, SMS Medical College, Jaipur, India
2 Assistant Professor, Department of Pediatrics, SMS Medical College, Jaipur, India
3 Consultant Pediatric Intensivist, Department of Pediatrics, SMS Medical College, Jaipur, India
4 Resident, Department of Pediatrics, SMS Medical College, Jaipur, India
|Date of Submission||15-May-2017|
|Date of Acceptance||26-Jun-2017|
|Date of Web Publication||20-Jul-2017|
Consultant Pediatric intensivist, Department of Pediatrics, SMS Medical College, Jaipur
Source of Support: None, Conflict of Interest: None
Beta thalassemia with hereditary persistence of fetal hemoglobin (HPFH) is a rare disease with a clinical presentation different from thalassemia major and HPFH. The association of HPFH with beta-thalassemia mitigates the clinical manifestations which vary from a normal state to beta-thalassemia intermedia. HPFH is due to deletions in the beta-globin gene cluster or point mutations in the HBG1 and HBG2 genes (11p15.5). We are reporting a case of 6 year male child with compound heterozygous for HPFH and beta Thalassemia with Moya-moya disease. Elder sister was also compound heterozygous for HPFH and beta Thalassemia intermedia. Father was having beta Thalassemia trait and mother having HPFH.
Keywords: Beta thalassemia intermedia, HPFH, Moya-Moya disease.
|How to cite this article:|
Gupta A, Mathur P, Sharma M, Parmar V. A rare case of compound heterozygous B-thalassemia and hereditary persistence of fetal hemoglobin with Moya-Moya disease. J Pediatr Crit Care 2017;4:110-3
|How to cite this URL:|
Gupta A, Mathur P, Sharma M, Parmar V. A rare case of compound heterozygous B-thalassemia and hereditary persistence of fetal hemoglobin with Moya-Moya disease. J Pediatr Crit Care [serial online] 2017 [cited 2023 Feb 5];4:110-3. Available from: http://www.jpcc.org.in/text.asp?2017/4/3/110/281381
| Introduction|| |
Beta thalassemia with hereditary persistence of fetal hemoglobin HPFH is a rare disease with a clinical presentation different from thalassemia major and HPFH. The association ofHPFH with beta-thalassemia mitigates the clinical manifestations which vary from a normal state to beta-thalassemia intermedia. HPFH occurs due to deletions in the beta-globin gene cluster or point mutations in the HBG1 and HBG2 genes (11p15.5). Association of compound heterozygous HPFH and beta-thalassemia with Moya Moya disease is very rare occurrence.
| Case Report:|| |
A 6 year male child, born out of non-consanguineous couple presented with complaints of pallor and easy fatigability since the 3 years of age. Child also had complaint of fever and left sided hemiparesis with left sided facial weakness for 3 days.
Child also had history of hospitalization 1 month back for pallor and easy fatigability and received blood transfusion twice. There was no history of recurrent vomiting, recurrent diarrhea and constipation, yellowish discoloration of skin and eyes and recurrent blood loss. Birth history and development history were normal. Dietary history was normal. There was no history of blood transfusion in any other family member.
On physical examination, there was severe pallor, no icterus, no clubbing, no cyanosis, no lymphadenopathy and no edema. Vitals were stable and anthropometric parameters were within normal range. On per abdomen examination spleen was palpable 7 cm below costal margin and was firm in consistency. Liver was palpable 5 cm below costal margin with liver span of 11 cm, firm in consistency, tender to touch and with round margins.
On neurological examination child was having normal mental function and speech. On cranial nerve examination child was having left sided facial nerve palsy. Motor system examination revealed decreased tone and power (3/5) in left upper and lower limb. Plantar was extensor at left lower limb but flexor at right lower limb. Involuntary movements were absent. Sensory system examination was normal. Signs of meningeal irritation and cerebellar signs were absent. Autonomic system examination was also normal.
Elder sister was also having mild splenomegaly and hemolytic facies.
Laboratory investigations were done. CBC of child at the time of admission revealed, Hemoglobin- 2.3gm/dl, TRBC-1.01 million /cu. mm, TLC-8730/ cu. mm, MCV-79.2 microlitre, MCH-22.8 picogram, MCHC-28.8, Platelets-1,80,000/cu. mm, RDW-26.6 and reticulocyte counts were-0.2%. Peripheral blood smear examination revealed reduced red cell count, predominantly microcytic hypochromic cells, macro- ovalocytes, marked anisocytosis and poikilocytosis. Iron studies were within normal limits. PT/INR and aPTT were normal. Thalassemia was suspected from above findings and High performance liquid chromatography (HPLC) was done. HPLC report revealed that child was compound heterozygous for HPFH and beta Thalassemia.
CBC of elder sister revealed Hemoglobin-8gm/dl, TRBC-3.71million/cu.mm, MCV-79.8fl, MCH-21.6 pg and MCHC-27. HPLC showed HbA-0.1%, HbA2- 2.4%, HbF-101.3 which was suggestive of compound heterozygous for HPFH and beta Thalassemia.
CBC of mother revealed Hemoglobin- 10.9gm%, TRBC-4.96million/cu.mm, MCV-66.7fl, MCH-22pg, MCHC-33.9. HPLC showed HbA-74.2%, HbA2- 2.8% and HbF-15% which was suggestive of HPFH.
CBC of father revealed Hb-11.8gm%, TRBC- 5.71 million/cu.mm, MCV-63.9fl, MCH-20.7pg and MCHC-32.3. HPLC showed HbA-82.1%, HbA2- 5.8% and HbF-2.2% which was suggestive of beta Thalassemia trait.
MRI brain [Figure 1] of the patient revealed multiple tiny hyperintensities in bilateral centrum semiovale and deep white matter of fronto-parietal lobes suggestive of acute watershed infarcts. MR Angiography [Figure 2] was puff of smoke appearance which was suggestive of bilateral Moya-Moya disease.
The child was managed with packed red blood cell transfusion and symptomatic-supportive treatment. Child is improved gradually over a period of 10 days.
| Discussion:|| |
Beta thalassemia presents with a spectrum of clinical features depending on the beta gene mutations and coinheritance with other haemoglobinopathies. Increased HbF level in adulthood can be due to congenital and acquired conditions. Heterozygous HPFH have an HbF level between10-35% and have benign course. When these people tie to another bearer of the beta globin mutation, the expression in offspring carrying a compound heterozygous genotype vary widely .
Thalassemia displays a great deal of phenotypic heterogeneity, despite being generally thought of as simple Mendelian diseases. The reasons for this are not well understood, although the level of fetal hemoglobin (HbF) is one well characterized ameliorating factor.
The role of increased HbF response as an ameliorating factor becomes evident in the group of homozygous β° thalassaemia patients who are not able to produce any haemoglobin A (α2β2) but have a mild disease with a reasonable level of haemoglobin, all of which is HbF. Production of fetal haemoglobin after the neonatal period in β thalassaemia is an extremely complex process and still poorly understood. There appears to be a genuine increase in γ chain synthesis, presumably reflecting the expansion of the ineffective erythroid mass. All β thalassaemias, heterozygous or homozygous, have variable increases in their levels of Hb F.,, There are undoubtedly genetic factors involved. Studies have shown that approximately 90% of the variation in the level of HbF and F cells (subset of erythrocytes that contain HbF) is genetically controlled. Detection of an inherent capacity for increased Hb F production is, at present, difficult and usually inferred from family studies.
Moya-Moya disease is a rare, progressive cerebrovascular disorder caused by blocked arteries at the base of the brain. In children, the first symptom of Moya-Moya disease is often stroke, or recurrent transient ischemic attacks (TIA, commonly referred to as “mini-strokes”), frequently accompanied by muscular weakness or paralysis affecting one side of the body, or seizures. Moya Moya disease is the result of inherited genetic abnormalities.
Genetic variants implicated along with β thalassaemia are genetic variants in Factor V, prothrombin and methylenetetrahydrofolate reductase, which can cause increased risk of thrombotic complications.
| Conclusion:|| |
Till now it is believed that co-inheritance of HPFH and beta thalassemia reduces disease severity and complications, but it may sometimes have associated with rare complications like Moya Moya disease. HPLC and Molecular studies in patient, sibling and parents are essential to clinch the diagnosis and prevention in subsequent pregnancies.
Conflict of Interest: None
Source of Funding: None
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[Figure 1], [Figure 2]