What is the Difference Between Alkaptonuria and Phenylketonuria

The key difference between alkaptonuria and phenylketonuria is that alkaptonuria is an inherited genetic disorder that results from the inability to metabolize the two amino acids, tyrosine and phenylalanine, while phenylketonuria is an inherited genetic disorder that results from the inability to metabolize the amino acid phenylalanine.

Inborn errors of metabolism are rare inherited genetic disorders. In these conditions, the body cannot properly turn food into energy. The disorders of inborn errors of metabolism are normally caused due to defects in specific enzymes that help to break down parts of food. There are many different types of inborn errors of metabolism. Some of them are fructose intolerance, galactosemia, maple sugar urine disease, alkaptonuria, and phenylketonuria.

CONTENTS

1. Overview and Key Difference
2. What is Alkaptonuria 
3. What is Phenylketonuria
4. Similarities – Alkaptonuria and Phenylketonuria
5. Alkaptonuria vs Phenylketonuria in Tabular Form
6. Summary – Alkaptonuria vs Phenylketonuria

What is Alkaptonuria?

Alkaptonuria is an inherited genetic disorder that results from the inability to metabolize two amino acids: tyrosine and phenylalanine. It is a type of inborn error of metabolism. This disorder is due to a mutation in a gene called HGD, which is responsible for making an enzyme known as HGD (homogentisate 1, 2-dioxygenase). The HGD enzyme is involved in the metabolism of the aromatic amino acids tyrosine and phenylalanine. People who have HGD mutation cannot metabolize homogentisic acid generated from tyrosine into 4-maleylacetoacetate. This defect results in the accumulation of homogentisic acid in blood and tissues. Moreover, in this condition, homogentisic acid and its oxidized form (alkapton) are excreted in the urine, which gives an unusually dark colour to urine.

The sign and symptoms include darkly stained tissues in the body, joint and bone problems (osteoarthritis), thickening and blue-black discolouration of ear cartilage (ochronosis), black or reddish-brown ear wax, brown or grey spots on the whites of the eyes, discoloured sweat, blue or black speckled areas of skin, bluish colour nails, breathing difficulties, heart problems (harden heart valves and stiff blood vessels), kidney stones, bladder stones, and prostate stones. The diagnosis of this condition can be made through physical examination, detailed patient history, urine test, gas chromatography to test traces of homogentisic acid, and DNA test to check mutation of HGD gene. Furthermore, treatment options include giving nisitone to reduce homogentisic acid in the body, restricting proteins in the diet, exercise for pain and stiffness, and pain relief through pain killers.

What is Phenylketonuria?

Phenylketonuria is an inherited genetic disorder that results from the inability to metabolize only one amino acid: phenylalanine. This condition is usually due to a mutation in a gene known as PAH, which encodes for an enzyme known as phenylalanine hydroxylase. This enzyme is necessary to metabolize amino acid phenylalanine to the amino acid tyrosine. When phenylalanine hydroxylase activity reduces due to mutation, phenylalanine accumulates and is converted into phenylpyruvate (phenylketone), which can be detected in urine.

The sign and symptoms of this disorder may include musty odour in sweat, skin, or urine, neurological problems including seizures, fair skin and blue eyes, abnormally small head, hyperactivity, intellectual disability, delayed development, behavioural, emotional, social problems, and psychiatric disorders. The diagnosis is performed through newborn blood testing, clinical evaluation, and DNA testing for gene mutation. Furthermore, the treatment is mainly through diet regulation, which includes food containing low phenylalanine levels (restricting proteins) and special formula for babies with a small amount of breast milk. The medication sapropterin dihydrochloride may also be useful in some cases. This medication is a cofactor for the enzyme phenylalanine hydroxylase, which enhances its activity.

What are the Similarities Between Alkaptonuria and Phenylketonuria?

• Alkaptonuria and phenylketonuria are two inborn errors of metabolism.
• Both are inherited genetic disorders.
• These disorders follow autosomal recessive inheritance.
• Both disorders lead to the accumulation of metabolites in body tissues.
• They are mainly treated by restricting high protein-based diets.

What is the Difference Between Alkaptonuria and Phenylketonuria?

Alkaptonuria is an inherited genetic disorder that results from the inability to metabolize the two amino acids, tyrosine and phenylalanine, while phenylketonuria is an inherited genetic disorder that results from the inability to metabolize the amino acid phenylalanine. Thus, this is the key difference between alkaptonuria and phenylketonuria. Furthermore, alkaptonuria global prevalence is 1 in 250000 to 1000000 live births, while global phenylketonuria prevalence is 1 in 23930 live births.

The below infographic presents the differences between alkaptonuria and phenylketonuria in tabular form for side by side comparison.

Summary – Alkaptonuria vs Phenylketonuria

Inborn errors of metabolism are rare inherited genetic disorders. Alkaptonuria and phenylketonuria are two inborn errors of metabolism. Alkaptonuria results from the inability to metabolize two amino acids tyrosine and phenylalanine while phenylketonuria results from the inability to metabolize the amino acid phenylalanine. So, this summarizes the difference between alkaptonuria and phenylketonuria.

Reference:

1. “Alkaptonuria.” NHS Choices, NHS.
2. “Phenylketonuria (PKU).” Mayo Clinic, Mayo Foundation for Medical Education and Research.

Image Courtesy:

1. “OCHRONOSIS” By Universidad CES – (CC BY 3.0) via Commons Wikimedia
2. “Inborn errors of metabolism of phenylalanine and tyrosine” By Bradford Morris – Own work (CC BY-SA 4.0) via Commons Wikimedia