Phenylketonuria vs Alkaptonuria | Causes, Symptoms & Biochemical Basis

Phenylketonuria (PKU) and Alkaptonuria | Complete Breakdown of Amino Acid Metabolism Disorders

Welcome to our detailed exploration of Phenylketonuria (PKU) and Alkaptonuria, two classic examples of inborn errors of metabolism that arise due to disruptions in the phenylalanine and tyrosine degradation pathways. These genetic disorders may be rare, but they hold profound importance in both biochemistry and clinical medicine.

In this video, we guide you through the biochemical mechanisms, genetic mutations, clinical presentations, and management of these two conditions. Using clear visuals and simplified explanations, we connect the dots between enzymatic deficiencies and their systemic effects.

🔍 What You Will Learn:
🔹 Phenylketonuria (PKU):

Caused by a deficiency of the enzyme phenylalanine hydroxylase

Leads to the accumulation of phenylalanine, which is toxic to the developing brain

Symptoms include intellectual disability, microcephaly, seizures, hypopigmentation, and a musty odor of the urine

Importance of newborn screening and early dietary phenylalanine restriction

Role of tetrahydrobiopterin (BH4) in some cases (mild/malignant PKU)

🔹 Alkaptonuria:

Results from a mutation in the HGD gene, causing a deficiency of homogentisate oxidase

Leads to the buildup of homogentisic acid (HGA), which oxidizes and polymerizes into a dark pigment

Classic features: dark urine, ochronosis (bluish-black pigmentation of connective tissues), and early-onset arthritis

Slow-progressing but often not detected until adulthood

Current treatment is largely supportive, with research ongoing into nitisinone therapy to block upstream accumulation

🔄 Comparison and Clinical Significance:
We compare both disorders in terms of:

Genetic inheritance (both autosomal recessive)

Enzyme involvement

Clinical onset and symptoms

Long-term consequences if untreated

Diagnostic tests: Ferric chloride test, urinary HGA detection, newborn screening programs

Biochemical pathway: How a disruption in phenylalanine metabolism at different steps leads to distinct diseases