Abstract
OBJECTIVE: Alkaptonuria is a rare inborn error of metabolism, with few reports from Brazil and typically lacking genotype descriptions in the Brazilian population. METHODS: A retrospective study of clinical and molecular data of individuals with alkaptonuria submitted to whole genome sequencing. RESULTS: Five individuals from four unrelated families were enrolled, with ages ranging from 8 months to 61 years at first evaluation and currently ranging from 26 to 65 years. All presented a history of dark urine since infancy and accentuated elevation of homogentisic acid excretion in urine samples. In two consanguineous families from the State of Bahia, the c.847 A > T and c.899 T > G variants were identified in homozygous status in the HGD gene; one of the individuals also had a history of infertility and presented the homozygous c.537 + 1G > A variant in the STX2 gene. The two remaining families without consanguinity, both from the State of São Paulo, presented with a combination of the heterozygous variants c.508G > A and c.899 T > G in one individual, and deletion of exon 13 of the HGD gene in trans with the c.1007-172 A > G deep intronic variant as a possible causative variant in another patient. CONCLUSIONS: Although small, the present series represents the first cohort of Brazilian individuals with alkaptonuria investigated by genomic sequencing, identifying a common variant (c.899 T > G) in two families and three exonic and one deep intronic variant in the HGD gene, besides a possible double diagnosis comprising infertility due to a homozygous variant of uncertain significance in the STX2 gene.