Haemoglobin is the specialised oxygen transport protein found packed inside red blood cells. During distinct stages of development, from embryonic to foetal and adult life, various types of haemoglobin are produced, each serving specific functions.
However, disruptions in the genetic make-up can lead to haemoglobin disorders, among which thalassaemia stands out as a prevalent concern.
Beta thalassaemia, a form of thalassaemia, ranks among the most common inherited blood disorders worldwide, with an incidence rate of 15.9 per 100,000 newborns in Mediterranean countries. This condition arises from mutations in the human globin genes, impairing the production of haemoglobin and consequently resulting in anaemia.
In Malta, approximately 40 individuals suffer from beta thalassaemia major and are dependant on lifelong blood transfusions every four to six weeks for survival. The management of such patients poses significant challenges, with complications including iron overload and risk of transfusion-transmitted infections. Moreover, curative options, such as bone marrow and haematopoietic stem cell transplantation, remain limited to a small subset of patients, underscoring the urgent need for innovative and sustainable approaches in treatment and care.
In Malta, approximately 40 individuals suffer from beta thalassaemia major and are dependant on lifelong blood transfusions every four to six weeks for survival
Recent investigations have shed light on a fascinating phenomenon – individuals with elevated levels of foetal haemoglobin (HbF) alongside pathological haemoglobin disorders like beta thalassaemia major, present with reduced clinical symptoms and an enhanced quality of life.
This discovery highlights the potential for novel therapeutic interventions by understanding the molecular mechanisms driving increased HbF levels. One such benign genetic condition is hereditary persistence of foetal haemoglobin (HPFH), characterised by continuous production of high HbF levels throughout adulthood. Notably, in Malta, five families are known to be affected by HPFH.
During my master’s research, under the supervision of Prof. Joseph Borg, my focus centred on unravelling the genetic complexities of HPFH within three Maltese families.
I identified a set of unique mutations present across all HPFH-affected individuals, and novel mutations within the NLRP3 and RPS9 genes emerged as potential players in sustaining elevated HbF levels. Furthermore, through proteomic analysis, I identified 53 proteins exhibiting significant correlation with HbF levels in HPFH-affected subjects, suggesting their potential involvement in the regulation of globin genes.
These findings not only deepen our understanding of HPFH but also pave the way for the development of targeted therapeutic interventions aimed at improving the lives of patients affected with haemoglobin disorders.
The work carried out in this master’s dissertation was funded by the Tertiary Education Scholarships Scheme, financed by the ministry for education and employment in Malta.
Nikita Camilleri completed a master of science degree in applied biomedical science at the Faculty of Health Sciences, University of Malta, and is currently a medical lab scientist at Mater Dei Hospital.
Sound Bites
• Survey of human diversity yields millions of previously unknown genetic variants: Up to 245,000 genomes were gathered by the ‘All of Us’ programme and run by the US National Institutes of health in Maryland. The analysis of these genomes has uncovered more than 275 million new genetic markers, of which a number contribute to type 2 diabetes. The findings were published on February 19 in a package of papers in Nature Communications Biology and Nature Medicine.
https://www.nature.com/articles/d41586-024-00502-0
For more soundbites, listen to Radio Mocha every Saturday at 7.30pm on Radju Malta and the following Monday at 9pm on Radju Malta 2 https://www.fb.com/RadioMochaMalta/.
DID YOU KNOW?
• Beta thalassaemia is more prevalent in regions where malaria is endemic! Researchers suggest that the genetic mutation responsible for beta thalassaemia provides protection against the Plasmodium parasite, which is responsible for causing malaria. This is because the abnormal red blood cells in individuals with thalassaemia make it more difficult for the malaria parasite to multiply and cause severe illness. Hence, individuals with beta thalassaemia trait have a survival advantage in regions where malaria is endemic.
• Thalassaemia can manifest with varying degrees of severity, ranging from mild to severe forms of the condition! The severity depends on the specific genetic mutations involved and their impact on the production of haemoglobin. Individuals with mild forms of thalassaemia may experience few or no symptoms, while those with severe forms of thalassaemia rely on lifelong medical management for survival.
For more trivia, see: www.um.edu.mt/think.