Homocystinuria in a consanguineous indigenous family from rural Honduras: a ten-year follow up and literature review of familial cases

Homocystinuria (HCU) is a rare autosomal recessive metabolic disorder, characterized by a mutation in the enzyme cystathionine beta-synthase and abnormally high levels of homocysteine in the blood. HCU that runs in a family is rare; prior to this report, there have been only 150 familial cases described in the literature. Here, we describe a familial cluster of HCU in four children in "Family V," a consanguineous indigenous family from rural Honduras with a 10-year clinical follow up. We describe the diagnosis, presentation and progression of three patients who were diagnosed in 2015; critical findings include substantial vision loss in Patients 1 and 2, and a significant decline in language ability in Patient 3. We also describe the presentation of Patient 4, a grandchild who we diagnosed with probable HCU based on symptoms very similar to his siblings and highly suspicious for HCU. Additionally, we completed a narrative review of previously published familial HCU cases, using PubMed and Google Scholar, to highlight common phenotypic trends in familial HCU patients. In the reported familial cases, 57% had CNS complications, 48% had ocular complications, and 30% had cardiovascular complications.