Homogentisate 1,2-dioxygenase (HGD) is a cytosolic enzyme that catalyzes the conversion of homogentisate to maleylacetoacetate, a critical step in the degradation pathway of the amino acids tyrosine and phenylalanine 1. The HGD gene is located on chromosome 3 and encodes a 445-amino acid protein 2. Pathogenic variants in HGD cause alkaptonuria (AKU), a rare autosomal recessive metabolic disorder characterized by deficient HGD enzyme activity and accumulation of homogentisic acid (HGA) in tissues 13. This accumulation leads to complications in joints, heart valves, and kidneys 3. Over 28 novel HGD variants have been identified globally, including missense mutations, splicing variants, and genomic deletions 1. Notably, genotype-phenotype correlation studies reveal that HGD variants causing 1% versus >30% residual enzyme activity produce small but statistically significant differences in urinary HGA excretion; however, dietary protein intake is more important than HGD variant type in determining HGA accumulation 1. Certain populations, including nomadic groups in India and Slovakia, exhibit elevated AKU prevalence (1:19,000) due to founder effects and consanguinity 4. The recent availability of nitisinone as a therapeutic option underscores the clinical importance of early genetic confirmation for AKU patients to prevent serious complications 3.