P44 Homocystinuria is a rare cause of fracture in young patients: a case report

Abstract

Abstract Background Homocysteinuira is a rare autosomal recessive disorder in the metabolism of sulfur-containing aminoacid caused by mutations in the cystathionine beta-synthase gene which encodes the pyridoxine dependent enzyme cystathionine beta-synthase. It is characterised by significant elevations in plasma and urine homocysteine concentrations and fractures. Methods We describe a case of homocysteinuira in a patient who suffered from a low impact patellar fracture, along with a literature review highlighting the critical relationship between homocysteine level and bone health. Results We reported a 36-year-old female with homocysteinuira due to pyridoxine (B6) unresponsive severe Cystathionine Beta-Synthase deficiency. She developed a right patellar low-impact fracture with osteopenia on X-ray. Examination revealed severe scoliosis with bilateral aphakia (absence of the lens of the eye). Her labs showed, persistent high homocysteine above 100 umol/L (4-10), methionine 383 umol/L (10-42), vitamin D 12 ng/ml. Her spine X-ray revealed severe scoliosis with osteopenia but no fracture. Her DXA scan showed her Z-Score was within the expected range for her age in hip, spine and 1/3 radius areas, however her ultra-distal radius Z-Score was -4.0. Her homocysteine level was mostly higher than 100 due to non-compliance with dietary advice and treatment. The severity of complications primarily depends on the age at diagnosis and the residual cystathionine beta-synthase activity. Most homocysteinuira patients diagnosed in adulthood have severe osteoporosis. Notably, a thinning and lengthening of the long bones result in tall and thin individuals with an appearance like that of Marfan’s syndrome. However, osteoporosis, particularly of the spine, which is associated with scoliosis, is one of the distinguishing features of the disease. High homocysteine levels in homocysteinuric patients impair the function of bone cells that regulate bone remodeling as well as bone material properties such as collagen cross-linking. This imbalance between bone formation and resorption may lead to a low BMD and fracture in patients with. Interestingly, even in general population hyperhomocysteinemia with a plasma level of more than > 13 nmol/ml has been found to be associated with low BMD and an increased risk of fractures that is independent of BMD. Deficiencies in vitamin B6, B12, or folate can lead to increased serum levels of homocysteine as these vitamins act as co-factors for various enzymes involved in homocysteine metabolism. This can be easily rectified with dietary intervention. Conclusion In young patients with a fracture or low BMD, hyperhomocysteinemia could play an important role in the pathogenesis. Homocysteine level should be included in the work up for secondary osteoporosis at young age-group. Simple dietary measures and vitamin B6, folate and B12 supplement should be considered as adjuvant therapeutic option for lowm BMD patients if deficient. Possibly the BMD of the ultra-distal radius is the most sensitive to detect bone changes in hyperhomocysteinemic patients. Disclosures A. Al-Allaf None. T. Paul None. B. Awadh None.