Think classical homocystinuria if the genetic test did not confirm Marfan syndrome: Late diagnosis and phenotypic variability in adult siblings with classical homocystinuria.

ABSTRACT: Classical homocystinuria is an inherited metabolic disease of homocysteine metabolism due to biallelic pathogenic variants in CBS. The biochemical hallmark is elevated homocysteine and methionine levels. The treatment consists of betaine supplementation and protein restricted diet. We report two adult siblings with late diagnosis of classical homocystinuria, a variable phenotype and good response to the treatment. Patient 1 is a 29-year-old female with a history of myopia, Marfanoid habitus with significant kyphoscoliosis, anxiety and a psychotic episode. Clinical exome sequencing identified compound heterozygous pathogenic variants in CBS (c.209+1G>A; c.992C>T (p.Ala331Val)). She had markedly elevated homocysteine (298 μmol/L) and methionine (1040 μmol/L) levels. Her brain m

SUBMITTER: Sultan R 

PROVIDER: S-EPMC12549521 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature