Here, Mellin-Sanchez and Sondheimer have identified a patient with not only vitamin B12 deficiency (affecting methionine synthetase and methylmalonyl-CoA mutase, increasing his total homocysteine and methylmalonic acid levels) but also cystathionine [beta]-synthase (CBS) deficiency leading to homocystinuria.
Reports exist describing increases in homocysteine and methylmalonic acid in refugees, most recently from Syria, who have B12 deficiency and malnourishment (1). The astute physicians in this case also noticed an unusually high level of methionine (before and after initiation of cobalamin) and continued high concentrations of total homocysteine; these findings indicated a separate biochemical abnormality, CBS deficiency.
The recent guideline published by Morris et al. recognizes an increased risk for CBS deficiency if total homocysteine concentrations are higher than 100 [micro]mol/L and there are increased methionine levels. Individuals can also present with physical examination findings including skeletal abnormalities, ectopia lentis (usually after 2 years of age), thromboembolic events, and central nervous system sequelae (with developmental delay or intellectual disability and behavioral issues) (2).
This patient was started on a methionine-restricted diet, betaine, and folate and is now doing well. Patients who are maintained with free homocystine concentrations of 11 [micro]mol/L or less (about 110-120 [micro]mol/L total homocysteine) in the first 4 years of life have normal intellect (2), which is good news for this patient. Treating the B12 deficiency was essential for this patient, as control of total homocysteine cannot occur in CBS deficiency if B12 is deficient (2).
The patient described in the paper by Mellin-Sanchez and Sondheimer in this issue of Clinical Chemistry is a perfect example of how the most obvious and simpler diagnosis may not be the only one.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved.
Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Received May 11, 2018; accepted May 15, 2018.
(1.) Bucak IH, Almis H, Benli S, Turgut M. An overview of health status of Syrian refugee children in a tertiary hospital in Turkey. Avicenna J Med 2017;7:110-4.
(2.) Morris AA, Kozich V, Santra S, Andria G, Ben-Omran TI, Chakrapani AB, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis 2017;40:49-74.
Kimberly A. Chapman *
Children's National Medical Center, Washington, DC.
* Address correspondence to the author at: 111 Michigan Ave NW, Washington, DC 20010. Fax 202-476-2390; e-mail Kchapman@childrensnational.org.
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|Title Annotation:||Clinical Case Study|
|Author:||Chapman, Kimberly A.|
|Date:||Nov 1, 2018|
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