What is the Difference Between Phenylketonuria and Alkaptonuria

The main difference between phenylketonuria and alkaptonuria is that phenylketonuria occurs due to a mutation of the PAH gene, whereas alkaptonuria occurs due to a mutation of the HGD gene.  

Phenylketonuria and alkaptonuria are two inherited autosomal recessive genetic disorders.      

Key Areas Covered

1. What is Phenylketonuria
– Definition, Features, Importance
2. What is Alkaptonuria
– Definition, Features, Importance
3. Similarities Between Phenylketonuria and Alkaptonuria
– Outline of Common Features
4. Difference Between Phenylketonuria and Alkaptonuria
– Comparison of Key Differences

Key Terms 

Alkaptonuria, Phenylketonuria

What is Phenylketonuria

Phenylketonuria is a genetic disorder that is autosomal recessive. Also, it is inherited. Significantly, it decreases the metabolism of phenylalanine. It causes intellectual disability, seizures, behavioral problems, and mental disorders. It results in lighter skin and a musty smell. The main cause of phenylketonuria is a mutation in the PAH gene, which encodes for the nonfunctional phenylalanine hydroxylase. The functional phenylalanine hydroxylase is responsible for the metabolism of excess phenylalanine. Therefore, in phenylketonuria, dietary phenylalanine builds up to potentially toxic levels.

Figure 1: Phenylalanine Hydroxylase Mutations

Furthermore, phenylketonuria is an autosomal recessive disease that holds the mutation in both copies of the gene. Also, there are two main types of phenylketonuria: classic phenylketonuria and variant phenylketonuria. They depend on the amount of activity of the phenylalanine hydroxylase gene remains.  

What is Alkaptonuria

Alkaptonuria is another genetic disorder caused by a mutation in the HGD gene. The gene encodes for the enzyme homogentisate 1,2-dioxygenase. It converts homogentisic acid to acetoacetic acid. The mutation in the gene causes the accumulation of homogentisic acid in blood and tissues. Then, homogentisic acid and its oxidized form, alkapton excreted in the urine. It gives an unnecessary dark color to the urine. Also, the accumulation of homogentisic acid causes cartilage damage and damage in heart valves. Homogentisic acid also precipitates kidney stones and other stones in other organs.

Figure 2: Homogentisate 1,2-Dioxygenase

Moreover, the symptoms of alkaptonuria develop in people over 30 years. Therefore, it is asymptomatic in young adults and children. But their urine becomes dark in color when exposed to open air. Additionally, pigmentations occur in the cartilage of the ear and other cartilage. 

Similarities Between Phenylketonuria and Alkaptonuria

• Phenylketonuria and alkaptonuria are two genetic disorders.
• They are inherited, autosomal recessive disorders.
• They occur due to mutations in both copies of the gene. 

Difference Between Phenylketonuria and Alkaptonuria

Definition

Phenylketonuria refers to a rare inherited disorder that causes an amino acid called phenylalanine to build up in the body. In contrast, alkaptonuria refers to a very rare inherited disorder that prevents the body from fully breaking down two protein building blocks (amino acids) called tyrosine and phenylalanine.

Gene Mutation

Phenylketonuria occurs due to the mutation in the PAH gene, while alkaptonuria occurs due to the mutation in the HGD gene. 

Location of the Defective Gene

The defective gene of phenylketonuria occurs in chromosome 12, while the defective gene of alkaptonuria occurs in chromosome 3. 

Defective Enzyme

Phenylalanine hydroxylase is the defective enzyme in phenylketonuria, while homogentisate 1,2-dioxygenase is the defective enzyme in alkaptonuria. 

Defective Function

The conversion of phenylalanine to tyrosine is the defective function in phenylketonuria, while homogentisic acid to acetoacetic acid is defective in alkaptonuria.

Function

Phenylketonuria decreases the metabolism of phenylalanine, while alkaptonuria accumulates homogentisic acid in the blood and tissues. 

Symptoms

Untreated phenylketonuria causes intellectual disability, seizures, behavioral problems, and mental disorders, while alkaptonuria causes damage to cartilage and heart valves, and kidney stones.  

Conclusion

In brief, phenylketonuria and alkaptonuria are inherited genetic disorders that occur due to mutations in both genes. Phenylketonuria occurs due to the presence of mutations in the PAH gene. It occurs in chromosome 12. The defective gene in phenylketonuria is phenylalanine hydroxylase which converts phenylalanine to tyrosine. Therefore, phenylketonuria decreases phenylalanine metabolism, causing intellectual disability, seizures, behavioral problems, and mental disorders. In comparison, alkaptonuria occurs due to a mutation in the HGD gene that occurs in chromosome 3. It encodes homogentisate 1,2-dioxygenase that converts homogentisic acid to acetoacetic acid. Therefore, alkaptonuria accumulates homogentisic acid in the blood and tissues, causing damage to cartilage and heart valves, and kidney stones. However, the main difference between phenylketonuria and alkaptonuria is the type of gene that contains the mutation.

References:

1. Mayo Foundation for Medical Education and Research. (2022a, May 13). Phenylketonuria (PKU). Mayo Clinic. 
2. (n.d.-a). Alkaptonuria. NHS choices. 

Image Courtesy:

1. “Phenylalanine hydroxylase mutations” By Thomas Shafee – Own work (CC-BY SA 4.0) via Commons Wikimedia
2. “Illustration of Homogentisate 1,2-dioxygenase ” By Michaelfusakio at English Wikipedia – Own Work (CC-BY SA 3.0) via Commons Wikimedia