Clinical and molecular characteristics of Chinese patients with alkaptonuria: 4-year follow-up of a pediatric patient and literature review

Alkaptonuria (AKU) is a rare autosomal recessive disorder of amino acid metabolism caused by defects in the <i>HGD</i> gene. The diagnosis of AKU is often delayed or missed due to its insidiousness. AKU is far from well-known in China. This study aims to provide an epidemiological synthesis of Chinese AKU patients. Firstly, we reported a Chinese pediatric AKU patient who visited because of short stature. Her urinary organic acid analysis revealed a small amount of homogentisic acid (HGA). Whole exome sequencing and Sanger sequencing revealed that the patient carried a c.343-1G > A/c.1027 A > C(p.Met343Leu) compound heterozygous variant in the <i>HGD</i> gene, which was inherited from her parents, respectively. During 4-year follow-up, a small amount of HGA was persistently present in her urine, whereas her height exhibited catch-up growth and subsequently normalized. According to the literature, 91 Chinese AKU patients, including the present one, were included. Among them, the male-to-female ratio was approximately 2:1, and the average age at diagnosis was 36.99 ± 23.05 years. The most common clinical feature was darkened urine (100.00 %), followed by arthropathy (69.23 %) and pigmentation of the skin or sclera (58.24 %). Pigmentation of the skin or sclera and arthropathy occurred more frequently in adult patients. Eleven different variants in the <i>HGD</i> gene were identified, including 5 known variants and 6 not listed in HGMD. This study describes a new Chinese AKU patient and summarizes the clinical and molecular features of Chinese AKU patients, which will help enrich the knowledge of AKU and contribute to early recognition, diagnosis and treatment.