Classical Homocystinuria in Adult Patients - One Centre Experience

BACKGROUND: Classical homocystinuria (HCU) is a rare autosomal recessive disorder of homocysteine metabolism caused by a deficiency of the pyridoxine-dependent enzyme, cystathionine beta-synthase, which converts homocysteine to cystathionine in the transsulphuration metabolic pathway. The disease manifests as early unprovoked thromboembolic (TE) events, subluxation of the lens (which is pathognomonic for the classical form of HCU) and various skeletal and connective tissue disorders such as osteopenia, vertebral fractures, and arachnodactyly. The disease is extremely rare in Croatia because there is no newborn screening for the disease. A few years ago, homocysteine was included in the panel for thrombophilia but in most cases, it is secondary hyperhomocysteinemia due to vitamin B12 or folic acid deficiency.

This study describes the characteristics of patients with HCU treated in our department.

METHODS: This retrospective study included four adult patients (3 men and 1 woman) who were treated in our department from 2012−2022. The diagnosis was based on laboratory findings of elevated homocysteine, elevated or normal methionine, normal B12 and folate, as well as a history of a thromboembolic event and subluxation of the lens.

RESULTS: The median age of the patients was 52. Three patients (75%) were diagnosed in childhood and one (25%) was diagnosed with the disease after a TE event. All patients have disease complications: 4 patients (100%) have subluxation of the lens, 2 patients had (50%) deep vein thrombosis, 2 patients (50%) had stroke, 1 patient (25%) had pulmonary embolism, 1 patient (25%) has osteoporosis, and 3 patients (75%) have osteopenia. All patients are pyridoxine non-responsive and are on therapy with betaine, folate, vitamin B12 and a low-protein diet. Regarding anticoagulant therapy, all patients are on warfarin. Two patients (50%) have excellent compliance and are well-regulated with a mean concentration of homocysteine of 28.58 µmol/L ±1.55 and a mean concentration of methionine of 56 µmol/L±5). The other two patients (50%) were poorly regulated with a mean concentration of homocysteine of 188 µmol/L ± 45.50 and a mean concentration of methionine of 778 µmol/L ± 68.

CONCLUSION: A small number of patients were included in this research, probably due to the lack of newborn screening for this rare disease, and mostly because of the reduced awareness of this disease. Patients who have good compliance are well-regulated without new TE events, whereas patients who are not poorly regulated are primarily due to dietary errors and not taking therapy regularly.