Homocystinuria a rare cause of low BMD in young patients: A case report with literature review


Homocystinuria a rare cause of low BMD in young patients: A case report with literature review


Abdul-Wahab Al-Allaf, Theresa Paul, Basem Awadh

Rheumatology Section, Department of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, POBOX 3050,Qatar


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Background: Homocystinuira is a rare autosomal recessive disorder in the metabolism of sulfur-containing amino acid caused by mutations in the cystathionine beta-synthase gene which encodes the pyridoxine (Vitamin B6) dependent enzyme cystathionine beta-synthase. It is characterized by significant elevations in plasma and urine homocysteine concentrations, which could be associated with increased risk of fracture.

Methods: We describe a case of Homocystinuria who suffered from a low impact patellar fracture with a literature review to highlight the critical relationship between homocysteine level and bone health.

Results: We reported a 36-year-old female with a diagnosis of Homocystinuria due to pyridoxine (B6) unresponsive severe Cystathionine Beta-Synthase deficiency. After a minor knee injury she developed a right patellar fracture and her X-ray revealed osteopenia. On examination, she has severe scoliosis in the spine with bilateral aphakia (absence of the lens of the eye). Her labs showed, persistent high Homocysteine above 100 umol/L, Methionine: 383 umol/L (10-42), Vitamin D 12 ng/ml. Her spine X-ray revealed very severe scoliosis with osteopenia but no vertebra 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 Homocystine level was mostly higher than 100 due to non-compliance with dietary advice and treatment. High homocysteine levels in Homocystinuric 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 homocystinuria. Interestingly, even in general population hyperhomocystinemia 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 bone mineral density, hyperhomocystinemia could play an important role in the pathogenesis. This should be included in the work up for secondary causes for osteoporosis for this age-group. Simple dietary measures and vitamin B6, folate and B12 supplement should be considered as adjuvant therapeutic option for any patient with osteoporosis and fractures, if deficient. Possibly the BMD of the ultra-distal radius is the most sensitive to detect bone changes in these patients.


Keywords: Homocystinuria, low BMD, young patients


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How to cite this article:

Abdul-Wahab Al-Allaf, Theresa Paul, Basem Awadh. Homocystinuria a rare cause of low BMD in young patients: A case report with literature review. International Journal of Case Reports, 2020 4:133. DOI: 10.28933/ijcr-2020-05-1305


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