An infant with a history of hypotonia, developmental delay, and inadequate nutrition was evaluated. The patient was the offspring of a consanguineous (first cousin) Syrian couple, born at term in Syria after an unremarkable pregnancy. His neonatal course was unremarkable.
Lizbeth Mellin-Sanchez1 and Neal Sondheimer1,2*
1Division of Clinical and Biochemical Genetics, The Hospital for Sick Children, Toronto, Canada; 2The Department of Paediatrics, The University of Toronto, Toronto, Canada.
*Address correspondence to this author at: 555 University Avenue, Toronto, ON M5G1X8. Fax 416-813-4940; e-mail firstname.lastname@example.org
An infant with a history of hypotonia, developmental delay, and inadequate nutrition was evaluated. The patient was the offspring of a consanguineous (first cousin) Syrian couple, born at term in Syria after an unremarkable pregnancy. His neonatal course was unremarkable. At the age of 7 months he presented with intermittent diarrhea, fever, and poor feeding. His symptoms progressed, and at 11 months (upon migration to Canada) he was admitted to the hospital for weight loss, decreased urine output, fever, and the loss of skills such as babbling, rolling over, or sitting without support. At the time of admission, he was only taking maternal breast milk.
Forty-eight hours after B12 administration and transfusion, his urine methylmalonate had normalized (Table 1). The methionine was now greatly increased at 781 μmol/L. His acylcarnitine profile had normalized. His total Hcy remained high at 146.1 μmol/L. He was started on vitamin B6 50 mg twice daily, and blood testing was repeated. These studies showed a sustained increase in total Hcy of 119μmol/L and a high methionine concentration of 917 μmol/L.
Questions to Consider
- What potential disorders are suggested by the increases in serum methylmalonate and plasma homocysteine concentrations?
- What is the most likely diagnosis given the increased methionine and plasma homocysteine concentrations after vitamin B12 administration?
- What testing could be done to confirm the patient’s diagnosis?
Final Publication and Comments
The final published version with discussion and comments from the experts appears in the November 2018 issue of Clinical Chemistry, approximately 3-4 weeks after the Student Discussion is posted.