HAEMOGLOBIN VARIANTS IN PREGNANT WOMEN ATTENDING ANTENATAL CLINIC

Haemoglobin variants in pregnant Women attending antenatal clinic in Jos University Teaching Hospital Jos.

CHAPTER ONE

  • INTRODUCTION

Haemoglobin variants are inherited disease caused by reduced or abnormal synthesis of globin.

Mutations in the globin genes are the most prevalent monogene disorders world wide and affects approximately 7% of the world’s population (Hoffbrand et al., 2006).

Haemoglobin pathy is defined as variation in the normal rate of synthesis or a complete absence of synthesis on continuous production of a normal developmental haemoglobin for change in the actual structure of haemoglobin e.g HbS and HbC.

Clinical effect of Hb variants results in the following:

  1. Altered physio co-chemical properties leading to haemolysis e.g. HbS which has decreased solubility upon deoxygination
  2. Decrease stability Haemoglobin with this change often precipitate within the Red blood cell leading to Heinz bodies and haemolytic anaemia.
  3. Altered oxygen binding these are variants with either high or low oxygen affinity
  • High oxygen variant manifest themselves with erythrocyte resulting from tissue hypoxia and stimulation of Epo production.
  • Low oxygen variant may cause mild anaemia and altered oxygen affinity usually result from substitution at the α1 β2 contact at the 2, 3 DPG binding site or at the carbon terminus of the β – chain.
  1. Met haemoglobin Result from the oxidation of haem iron to the ferric state majority of this have Histidine – Tyrosin sibstituttion either in the proximal or distal histidine clinically, the manifest as familial cyanosis.
  2. Some variants lead to a thalassaemia phenotype either as a result of reduce synthesis or as a result of globin hyper instability e.g.of reduce synthesis is HbE, Haemoglobin knowsses e.g. of globinopathy with globin herper instability is Hb Geneva.

Statement of Research Problem

  • Haemoglobin variant is a major cause of morbidity and mortality
  • Recent data estimates over 5.5million HbAS births and 313100 HbSS birth with 75% of those occurring in sub-Sahara, Africa. (Darlison, 2008).
  • Haemoglobin disorder causes a variety of syndromes all with anaemia as the common characteristic and with wide spectrum of clinical severity consequence.

Justification

  • Globally around 7% of pregnant women carry β and alpha zero thalassemia or haemoglobin S, C, D Punjab, E and over 1% of couples are at risk (WHO, 2015).
  • Carriers and couples at risk should be identified and informed of their   risk and option for reducing it by genetic counseling.
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Scope of Study

Haemoglobin genotype was carried on the blood sample of 126 pregnant women attending Ante-Natal clinic in Jos University Teaching Hospital.

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Hypothesis (Null Hypothesis)

There was no significant haemoglobin genotype among pregnant women in Jos University teaching hospital ante-natal clinic.

Specific Objective

To determine the prevalence of haemoglobin variants in pregnant women attending ante-natal clinic in Jos University Teaching Hospital.

To reduce the disease through genetic counseling.

To suggest prenatal diagnosis for couple at risk of having an affected child.

CHAPTER TWO

LITERATURE REVIEW

History of Haemoglobin Variants:

Haemoglobin variants are mutant forms of hemoglobin in a population (usually of humans) caused by variations in genetics. Some well-known hemoglobin variants such as sickle cell anaemia are responsible for diseases and are considered Haemoglobinopathies.  Other variants cause no detectable pathology, and thus considered non-pathological variants. Some normal haemoglobin types are; Haemoglobin A (HbA), which is 95-98% of haemoglobin found in adults, Haemoglobin A2 (HbA2) which is 2-3% which is found in adults, and haemoglobin F (HbF), which is found in adults up to 2.5% and is the primary haemoglobin that is produced by the foetus during pregnancy (Dacie and Lewis, 2006). Haemoglobin variant occurs when there are genetic changes in specific genes or globins that cause changes or alteration in the amino acid. They could affect the structure, behavior, the production rate, and or the stability of that specific gene. Usually there are four genes that code for alpha globin and two genes that code for beta globin. If the most common condition that occur is alpha thalassemia, which causes a decrease in production of that gene. The level of severity of alpha thalassemia is determined by the number of genes that are affected (Old et al., 1990).

Haemoglobin variants are most often inherited characteristics. First, abnormal beta gene can be inherited in an autosomal recessive fashion. This means that the person who inherits this will have two copies of the altered gene. Both of these genes can be passed to offspring’s. The next way they can be inherited is in a heterozygous fashion. This means the person has one normal beta gene and one abnormal beta gene. This person is considered to be a carrier of whichever haemoglobin variant is inherited. Only the abnormal gene can be passed on the offspring’s in this case, Carriers also do not have deal with having symptoms or any health concerns (Wealthral et al., 1992).

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Another way that beta genes can be inherited is in a homozygous fashion. This means that the person has two abnormal beta genes. In this case the person produces the associated haemoglobin variant and may have the symptoms and complications that are associated with specific haemoglobin variant they have. The severity of the conditions mainly depends on the genetic mutation and it may vary from person to person. The copies of the abnormal beta genes would be likely passed to offspring (Saiki et al., 1988).

The majority of these variant are beta chain variants mutation in the beta gene are mostly in an autosomal recessive fashion. A person inherit are copy of each beta globin gene from each parent. If one normal beta gene and one abnormal beta gene are inherited, the person is said to be a carriers or to be heterozygous for the abnormal haemoglobin. The abnormal gene can be passed unto any offspring but does not cause symptoms of health concern in the carrier (Chang et al., 1996).

Along with lengthy list of common haemoglobin variants, there are some variants that are considered silent, which means that they have no sign or symptoms. They usually affect the functionally and or the stability of the haemoglobin molecules with most of these variants are mutations in the alpha globin gene that result in an abnormally long chain and an unstable haemoglobin molecules (Ryan et al., 2010).

HEAMOGLOBIN

Haemoglobin is the iron-containing protein compound within red cells that carries oxygen throughout the body. It is a chromoprotein that contains four heme groups, which are the pigment containing parts and globin. A molecule of haemoglobin contains four polypeptides globin chain; α, β, γ and δ chains. Haemoglobin genotypes are inherited characters determine by different combinations of these chains. They includes HbAA, HbAS, HbAC, HbSC,HbSD,HbSE and HbSS (Hoffbrand et al.,2006). Haemoglobinopathies are inherited disorder of haemoglobin which are the genetically transmitted and are due to a single

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