Diseases of Gene Action in Man | Biochemical Genetics

The following points highlight the five major types of diseases of gene action in man. The types are: 1. Phenylketonuria 2. Alkaptonuria 3. Albinism 4. Tyrosinosis 5. Goitrous Cretinism.

Disease of Gene Action in Man: Type # 1. Phenylketonuria:

(i) Symptoms:

This disease is characterized by high level of phenylalanine in blood, spinal fluid and sweat. High level of phenylalnine in the blood leads to mental retardation and pale skin colour in the persons suffering from this disease.

(ii) Enzyme Involved:

This disorder is characterized by a deficiency in the enzyme phenylalanine hydroxylase (PAH). This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine. When PAH is deficient, phenylalanine accumulates and is converted into phenyl pyruvate (also known as phenyl ketone), which is detected in the urine. The gene for PKU is found on chromosome number 12.

(iii) Metabolic Pathway Blocked:

The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into the amino acid tyrosine. In this disease the conversion of phenylalanine into tyrosine is blocked, because enzyme becomes inactive.

(iv) Genetic Control:

This disease is caused by one pair of recessive gene. In homozygous condition, the gene inactivates the enzyme phenylalanine hydroxylase resulting in accumulation of high levels of phenylalanine. In heterozygous persons, less enzyme is produced than in normal person.

Phenylketonuria is one of the few genetic diseases that can be controlled by diet. A diet low in phenylalanine and high in tyrosine can be a very effective treatment. There is no cure. Damage done is irreversible so early detection is crucial.

Disease of Gene Action in Man: Type # 2. Alkaptonuria:

(i) Symptoms:

This disease is characterized by excessive secretion of alkapton or homogentisic acid in the urine. The urine of persons suffering from this disease turns black on exposure to the air. This disorder sometimes leads to mild arthritis due to deposition of acid crystals in the joints.

(ii) Enzyme Involved:

In normal persons, the homogentisic acid is converted into maleyl acetoacetic acid with the help of enzyme homogentisic acid oxidase. This enzyme becomes non­functional in the persons suffering from alkaptonuria.

(iii) Metabolic Pathway Blocked:

The conversion of homogentisic acid into maleyl acetoacetic acid is blocked. This leads to excretion of large amount of homogentisic acid into urine.

(iv) Genetic Control:

This disease is caused by one pair of recessive gene. In homozygous condition, the gene inactivates the enzyme homogentisic acid oxidase resulting in accumulation of homogentisic acid.

Disease of Gene Action in Man: Type # 3. Albinism:

(i) Symptoms:

This disease is characterized by albino condition. This disease leads to albino condition of skin, retina and hair.

(ii) Enzyme Involved:

Enzyme tyrosinase is associated with this disease. Inactivation of this enzyme leads to albinism.

(iii) Metabolic Pathway Blocked:

In normal persons, 3, 4 dihydroxy phenyalanine is converted into melanin with the help of enzyme tyrosinase. The enzyme tyrosinase becomes inactivated blocking above conversion.

(iv) Genetic Control:

This disease is caused by one pair of recessive gene. In homozygous condition, the gene inactivates the enzyme tyrosinase resulting in albino condition.

Disease of Gene Action in Man: Type # 4. Tyrosinosis:

(i) Symptoms:

This disease is characterized by excretion of P-dihydroxy phenyl pyruvic acid tyrosine in the urine. This disease does not produce any other serious symptom.

(ii) Enzyme Involved:

Enzyme P-hydroxy phenyl pyruvic acid oxidase is responsible for conversion of P-hydroxy phenyl pyruvic acid into 2, 5-dihydroxy phenyl pyruvic acid.

(iii) Metabolic Pathway Blocked:

In normal persons, P-hydroxy phenyl pyruvic acid is converted into 2, 5-dihydroxy phenyl pyruvic acid with the help of enzyme P-hydroxy phenyl pyruvic acid oxidase. This metabolic pathway is blocked due to inactivation of the enzyme.

(iv) Genetic Control:

This disease is caused one pair of recessive gene. In homozygous condition, the gene inactivates the enzyme P-hydroxy phenyl pyruvic acid oxidase resulting in tyrosinosis.

Disease of Gene Action in Man: Type # 5. Goitrous Cretinism:

(i) Symptoms:

This disease is characterized by severe physical and mental retardation and hypertrophy [enlargement] of thyroid gland.

(ii) Enzyme Involved:

Enzyme thyroid peroxidase is considered to be associated with this disease.

(iii) Metabolic Pathway Blocked:

The conversion of tyrosine into thyroxin and trodothyroxine [thyroid hormones] is blocked due to inactivation of the enzyme.

(iv) Genetic Control:

This disease is caused by one pair of recessive gene. In homozygous condition, the gene inactivates the enzyme resulting in severe expression of the disease. In heterozygous condition, there will be mild expression of the disease.