Phenylketonuria, Albinism, Alkaptonuria Case Studies

Phenylketonuria

Case 1: Mental Retardation

5 years old boy was brought to the hospital with complaints of mental retardation, failure to thrive, hypo-pigmented patches all over the body and a mousy odour of urine. On examination his eyes were blue. He had episodes of seizures in the past.

• Diagnosis– Phenylketonuria.
• It is an inborn error of the amino acid metabolism of phenylalanine and tyrosine.
• Deficient enzyme– phenylalanine hydroxylase.

Read And Learn More: Biochemistry Clinical Case Studies With Answers

Phenylketonuria

• Autosomal recessive disorder.
• Incidence– 1 in 10,000 births.
• Due to a deficiency of phenylalanine hydroxylase, Phenylalanine is diverted to the alternate pathway and gives phenylpyruvate, phenylacetate, phenylacetate and phenylacetylglutamine.
• Phenylpyruvate is a keto acid hence the name is given. The mousy odour is due to phenylacetate and other byproducts.
• Screening by– Guthrie test (bacterial inhibition assay– bacillus subtilis overcome the growth by using phenylalanine on an agar plate). Confirmatory diagnosis– Tandem mass spectrometry.

Phenylketonuria Treatment

1. Avoid Phenylalanine in diet (Commercial preparations are available in the market).
2. Avoid meat and poultry products.
3. Tyrosine becomes essential and has to be supplied in the diet.
4. Neurological manifestations are due to a decrease in the synthesis of dopamine, norepinephrine and epinephrine which are neurotransmitters in the CNS.
5. Also due to decreased serotonin production (due to ineffective tryptophan metabolism) and defective myelin formation.
6. Hypopigmentation is due to inhibition of tyrosinase involved in melanin formation.

Case 2: Phenylketonuria (PKU)

A 3-week-old female infant was diagnosed to have phenylketonuria (PKU).

Question 1. What is the screening test available? Discuss the genetics of the disease.
Answer:

• Screening test– Guthrie test.
• Genetics– autosomal recessive disorder, affecting 1 in 10000 live birth.

Case 3: Delayed Milestones

A one-year-old child with delayed milestones was brought to the hospital. His mother gave a history of mousy odour from diapers.

Question 1. What is the biochemical basis of diaper odour?
Answer:

The mousy odour of urine is due to phenylacetate excretion, giving the characteristic smell of a diaper.

Case 4: Phenylalanine And Low Level Of Tyrosine

A 2-week-old infant tested positive for the FeCl3 test on genetic screening for inborn errors of metabolism, lab data reveal increased serum phenylalanine and low level of tyrosine.

Question 1. What are the physiological consequences and why should they be detected as early as possible?
Answer:

• Accumulation of products due to phenylalanine hydroxylase deficiency leads to neurological manifestations over a period of time.
• If treated early, these symptoms can be prevented.

Albinism

Case 1: Photophobia And Nystagmus

A 25-year-old man came to the hospital with complaints of photophobia and nystagmus. He has hypopigmented skin, hair, and eyes.

• Diagnosis– Albinism.
• Deficient enzyme– Tyrosinase.

Albinism

It is an autosomal recessive disorder characterized by generalized hypopigmentation. Tyrosinase activity is totally absent, leading to defective melanin synthesis. Therefore, the baby mentioned in the case had white hair, blue eyes, and depigmented skin. Localized hypopigmentation is known as Vitiligo.

Albinism Clinical Manifestations

1. Photophobia.
2. Nystagmus (rapid involuntary eye movements).
3. Hypopigmented skin, hair, and eyes.
4. Increased susceptibility to skin cancer.

Case 2: Lack Of Pigmentation

A full-term baby born to normal and healthy parents was found to have a marked lack of pigmentation. The baby had white hair, blue eyes, and depigmented skin. There was no impairment in the eyesight of the baby. However baby was unable to tolerate light (Photophobia). The paternal grandfather of the baby had a similar problem.

Question 1. Describe the biochemical basis of symptoms observed in a child.
Answer: Tyrosinase is totally absent, leading to defective Melanin synthesis.

Alkaptonuria

Case 1: Black Discoloration Of The Ear And Nose

A 9-year-old child was brought to the hospital with complaints of black discoloration of the ear and nose. His urine turns black on standing. He also had a history of joint pain due to repeated arthritis. Urine examination showed an increased level of homogentisic acid.

• Diagnosis– Alkaptonuria.
• Deficient enzyme– Homogentisate oxidase.

Alkaptonuria

Autosomal recessive disorder.

Inborn error of Phenylalanine and tyrosine metabolism.

On standing, homogentisate gets oxidized to the corresponding quinones, which on polymerization gives black or brown color. Urine becomes dark on standing. Alkapton deposits in joints cause arthritis.

Case 2: Alkaptonuria Diagnosis

A patient was diagnosed as having ‘Alkaptonuria’.

Question 1 What is the possible treatment?
Answer:

1. No specific treatment is required.
2. A low phenylalanine diet is given.

Case 3: Suffering From Alkaptonuria

A mother takes her 3-year-old son to the OPD. After doing some tests, the doctors conclude that the child is suffering from Alkaptonuria.

Question 1. Name at least one test that can be done to confirm the above disease.
Answer:

• Urine gives a positive test with ferric chloride and silver nitrate.
• Benedict’s test on urine is positive for homogentisate.

Question 2. Give at least two characteristic symptoms of this disease.
Answer:

• Urine turns dark on standing.
• Arthritis due to alkapton deposition in joints.
• Black deposits in ear and nose.