Abstract Topic: 27. Thalassemias
Background: The Philippine prevalence of Thalassemia is not known.
Mutational variants in the hemoglobin genes have not been reported. These variants are unique for every population.
Thalassemia diagnosis and its impact on health can be explained by genotypic-phenotypic picture.
In the Philippines, underdiagnosis of thalassemia and the lack of documentation of the underlying genetic aberration restricts the health sector from intensifying its effort in genetic counselling, doing population-based studies, and delivering comprehensive treatment and programs.
Aims: This study aims to identify the most common genotype among Filipino Thalassemic patients. To know the prevalence of genotype among Filipino Thalassemic patients and to know the prevalence of genotype among Filipino Thalassemic patients by age, sex, geographic location.
Methods: The database of the lab coordinator of Makati Medical Center for the Laboratory Thalassemia genotyping test done was reviewed from 2012 to 2022.
Results: A total of 666 patients were tested for Thalassemia genotypes from different areas of the country. Majority(86.04%) requested for the alpha thalassemia genotypes followed by Beta Thalassemia(13.96%). The rest was tested for both.
The youngest patient tested was 1 month old while the oldest is 84 years old. Majority of the patient belongs to the 31- 40 and 21 - 20 years old age bracket (20.4%, 18.17%) respectively.
Majority(76.73%) of the patients tested are from the National capital Region, followed by Rizal area(6.91%), Cavite(5.26%) and Laguna(2.1%).
The negative test (N=205) reached 30.78% (ɑ,N=135,20.27%, β,N=70,10.51%). Positive test reached 69.22% (ɑ,N=438,65.77%, β,N=23,3.45%). Female tests positive more than male (M=34.49%, F=65.51%). Majority aged 21 to 40 years old (44.25%) then 41 to 60 years old (28.42%). The most common thalassemia subtype is alpha thalassemia. A total of 91% of the identified gene mutation is heterozygous while only 8% is homozygous to the specific mutation.
There were 21 alpha thalassemia genotypes identified. The most common is the SOUTH EAST ASIA GENE DELETION (37.98%,N=218) then FIL DOUBLE GENE DELETION (21.17%,N=140) then MUTATION -3.7 SINGLE GENE DELETION (4.7%, N=27), MUTATION -3.7 SINGLE GENE DELETION/ -- SEA DOUBLE GENE DELETION COMPOUND HETEROZYGOUS at 2.61% (N=15), MUTATION -3.7 SINGLE GENE DELETION/ -- FIL DOUBLE GENE DELETION COMPOUND HETEROZYGOUS (2.09%, N=12). The rest of the genotypes are below 1% (N=1-5).
There were seven Beta thalassemia genotypes identified. The most prevalent is MUTATION IN CODON 41/42 (-TTCT) (c.126 129delCTTT) HETEROZYGOUS (8.99%,N=8) then MUTATION IN CODON 17 [A>T] (C. 52A>T) HETEROZYGOUS (N= 4, 4.49%) then SOUTH EAST ASIA GENE DELETION (N=3, 3.37%), MUTATION IN IVS 2.654 [C>T] (c.316-197C>T) HETEROZYGOUS (N=2, 2.25%) (N=1, 1.12%) then MUTATIONs IN IVS 1.5 [G>C] (c. 92 + 5G>C) HETEROZYGOUS, MUTATION - 4.2 SINGLE GENE DELETION/ -- SEA DOUBLE GENE DELETION, COMPOUND HETEROZYGOUS, FIL DOUBLE GENE DELETION.
Summary/Conclusion: The result shows a 69.37% overall positivity rate in the PCR test. This shows the extent of affectation of the Filipino population by Thalassemia. The alpha thalassemia positive test is at 65.77% while beta thalassemia is at 3.45% of the total sample tested.
The most common genotype is the heterozygous SEA double gene deletion; the same findings was noted in Japan22, Vietnam, Cambodia, Laos, and Thailand9. The most common Beta thalassemia gene mutation is the MUTATION IN CODON 41/42 (-TTCT) (c.126 129delCTTT) HETEROZYGOUS which is the same as one in the south east Asian counterparts.14
Thalassemia is a heritable disease that can afflict a certain community mostly in the Philippines which is archipelagic where intrafamilial marriage may occur. It is an underdiagnosed disease. Screening and confirmatory tests are not readily available, expensive and requires technical expertise from the physician. Both alpha and beta genotypes identified are consistent with the neighboring southeast Asian nations.
Keywords: Gene mutation, Prevalence, Thalassemia