Autosomal Recessive Disorders - Alkaptonuria, Phenylketonuria, Albinism, Tay-Sach's disease, Cystic Fibrosis

Diseases that have autosomal recessive inheritance affect only individuals who have two defective copies of the gene (one from each parent).
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Autosomal Recessive Inheritance
Examples of Autosomal Recessive Disorders 
  • One of the first metabolic diseases described by Garrod in 1908
  • Due to deficiency of an oxidase enzyme required for breakdown of homogentisic acid (also known as alcaption). Lack of the enzyme is due to the normal form of gene that controls the synthesis of the enzyme. Hence accumulates in the tissues and is also excreted in the urine.
  • The most commonly affected tissues are cartilages, joints, ligaments and tendons.
  • The urine of these patients if allowed to stand for some ours in air, turns black due to oxidation of homogentisic acid.
  • Inborn metabolic disorder in which the homozygous recessive individual lacks the enzyme phenylalaine hydroxylase needed to change phenylalanine (amino acid) to tyrosine (amino acid).
  • Lack of the enzyme phenylalanine hydroxylase is due to the the abnormal autosomal recessive gene on chromosome 12.
  • In children, symptoms are mental retardation, decrease pigmentation of hair and skin and eczema.
  • The heterozygous individuals are normal but carriers.
  •    It occurs in about 1 in 18000 births among Europeans.
  • Albinism is characterized by the lack of dark pigment melanin in the skin, hair and iris.
  • Caused by the absence of thyrosinase which is necessary for the synthesis of the pigment melanin from dihydroxyphenylalanine.
  • The gene for albinism (a) does not produce the enzyme tyrosinase, but its normal allele (A) does.Thus, only homozygous individuals (aa) is affected.
Tay-Sach's disease (TSD)/ Infantile amourotic idiocy
  • Homozyous children show degeneration of central nervous system due to accumulation of a fatty substance (Sphingolipid) in nerve cells. This is caused by the enzyme D-N-acetyl hexosamindase which is normal individuals exists in two forms A and B.
  • In TSD, only A form is present, the B form is not present.
  • Children with Tay-Sach’s disease are born normal but develop severe brain and spinal cord damage in few months. The mentally retarded are progressively paralysed child dies in 3 or 4 years.    
  • In this disorder the breakdown of fatty acid substance is impaired leading to the accumulation of lipid materials in body tissues and blood.
  • It caused by the autsomal recessive gene which inhibits the activity of an enzyme glucocerobrosidase.Consequently there is accumulation of cerebroside (A sphingolipid)
  • Symptoms: Enlargement of spleen and liver and expansion of some of the limb bones.    
Thalassemia or Cooley’s anaemia or Thalassaemias major
  • Β-thalassemia was first described by Cooley
  • Thalassemia is characterised by the reduced synthesis of either the α and β chains of haemoglobin thalassemia.
  • The reduced synthesis of either alpha (beta chain) leads to the accumulation of alpha chains which cause damage to the precursors of red blood corpuscles in the bone marrow causing amemia
  • Homozygous individuals suffer from severe haemolytic anemia
  • Heterozygous individuals have the defect in a less severe from.
Cystic Fibrosis (CF)
  • Due to a recessive autosomal allele present on chromosome 7.
  • The defective gene in cystic fibrosis is the CTFR (CF transmembrane protein which acts as chloride channel.The CFTR protein removes chloride ions from cells and alters the sodium chloride balance reducing the viscosity of mucous secretions.
  • It produces a defective glycoprotein that causes formation of thick mucus in lungs, pancreas, liver skin and other secretory organs.
  •   In lungs thick mucus obstruct the pulmonary airways and often causes recurrent bacterial respiratory infection. Hence also called mucoviscidosis.
  • In pancreas, mucus deposition blocks secretion of pancreatic juice and may lead to maldigestion of food with high fat content in stool.
  • Liver may undergo cirrhosis and bile production may be impaired production of bile.
  • The sweat of the patient is saltier.
The frequency at birth of this disorder is 1 in 1800 among white people  and 1 in 100000 births among Africans and Asians. The carriers of the disease have increased resistance to cholera.

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