Question

A two-year-old child was taken to the hospital. His mother said that he vomited frequently, especially after feedings. The child's weight and physical development were below normal. His hair, although dark, contained patches of white. A urine sample treated with ferric chloride \(\left(\mathrm{FeCl}_{3}\right)\) gave a green color characteristic of the presence of phenylpyruvate. Quantitative analysis of urine samples gave the results shown in the table. a. Suggest which enzyme might be deficient in this child. Propose a treatment. b. Why does phenylalanine appear in the urine in large amounts? c. What is the source of phenylpyruvate and phenyllactate? Why does this pathway (normally not functional) come into play when the concentration of phenylalanine rises? d. Why does the boy's hair contain patches of white?

Short answer

The enzyme deficient is phenylalanine hydroxylase. Phenylalanine appears in urine due to its accumulation and excretion. White hair is due to reduced melanin from low tyrosine levels.

Step-by-step solution

Enzyme Deficiency Identification

The presence of phenylpyruvate in the urine is a hallmark of Phenylketonuria (PKU), a metabolic disorder. PKU is typically caused by a deficiency in the enzyme phenylalanine hydroxylase. This enzyme is responsible for converting phenylalanine to tyrosine, and its deficiency leads to the accumulation of phenylalanine in the body.

Suggested Treatment

The treatment for PKU is a low-phenylalanine diet, which helps to prevent the accumulation of phenylalanine and its byproducts in the body. Foods high in phenylalanine (such as many proteins) are restricted or carefully monitored.

Reason for Phenylalanine in Urine

In PKU, the conversion of phenylalanine to tyrosine is impaired due to the deficiency of phenylalanine hydroxylase. As a result, excess phenylalanine accumulates and is excreted in the urine, which is why it appears in large amounts.

Source of Phenylpyruvate and Phenyllactate

When phenylalanine is in excess and cannot be converted to tyrosine, alternative pathways become active. Phenylalanine is converted to phenylpyruvate (and further to phenyllactate) as a side pathway, leading to their presence in the urine.

Reason for Alternative Pathway Activation

The alternative pathway involving the conversion of phenylalanine to phenylpyruvate becomes functional due to feedback inhibition. The high concentration of phenylalanine inhibits the normal metabolic pathway, allowing other minor pathways to become more active.

Explanation for Hair Patches

In PKU, the decreased production of tyrosine (due to enzyme deficiency) affects melanin synthesis. Since melanin is derived from tyrosine, low levels of melanin lead to less pigmentation and result in patches of white hair.

Key concepts

Enzyme Deficiency

In the context of Phenylketonuria (PKU), enzyme deficiency plays a central role. PKU is a metabolic disorder primarily caused by the lack of an enzyme called phenylalanine hydroxylase. This enzyme is essential because it facilitates the conversion of phenylalanine, an amino acid, into tyrosine. Without sufficient phenylalanine hydroxylase, phenylalanine accumulates in the bloodstream, leading to a cascade of metabolic issues. This build-up results in the production of phenylpyruvate, a compound often detected in urine samples of individuals with PKU.

• High levels of phenylalanine disrupt normal bodily functions.
• Accumulation triggers toxic effects, contributing to symptoms such as developmental delays and neurological issues.
• Detection of phenylpyruvate in urine serves as a diagnostic indicator for PKU.

Understanding enzyme deficiency in PKU helps clarify why treatments focus on managing phenylalanine levels.

Phenylalanine Metabolism

Phenylalanine metabolism is a crucial process in the body involving the conversion of phenylalanine to tyrosine, which is facilitated by phenylalanine hydroxylase. Under normal circumstances, this conversion process enables the body to synthesize proteins and other vital compounds efficiently. However, in individuals with PKU, this metabolic pathway is disrupted due to the deficiency of the necessary enzyme.

• Instead of being converted, excess phenylalanine leads to the formation of alternative metabolites such as phenylpyruvate and phenyllactate.
• These alternative pathways become active when the primary metabolic route is inhibited or impaired.
• The body's attempt to metabolize excess phenylalanine through these backup pathways is less efficient, resulting in the accumulation and excretion of atypical metabolites.

By understanding these metabolic mechanics, one appreciates why monitoring and managing phenylalanine intake is vital for PKU patients.

Dietary Treatment

Dietary treatment for PKU is essential and revolves around minimizing phenylalanine intake. Since the body cannot adequately metabolize phenylalanine without the necessary enzyme, dietary adjustments become crucial to prevent harmful accumulations.

• A low-phenylalanine diet involves reducing or eliminating high-protein foods like meats, fish, eggs, and dairy.
• Specially formulated medical foods or protein substitutes may provide the necessary nutrients without the phenylalanine content.
• Regular monitoring of blood phenylalanine levels helps ensure the diet remains balanced and effective.

Such dietary strategies are critical in preventing the toxic effects associated with PKU and supporting normal development and health outcomes.

Melanin Synthesis

Melanin synthesis is affected in individuals with PKU due to the reduced conversion of phenylalanine to tyrosine. Tyrosine is a precursor for the production of melanin, the pigment responsible for coloration in hair, skin, and eyes.

• In PKU, insufficient tyrosine levels can result in diminished melanin production.
• This lack of melanin manifests in lighter pigmentation or white patches in hair, as seen in some PKU patients.
• Moreover, this symptom underlines the broader systemic effects of enzyme deficiencies on metabolic pathways.

Recognizing how melanin synthesis is compromised helps visualize the multisystem impact of PKU, highlighting the importance of early diagnosis and intervention.