Background Cobalamin metabolism defects are rare autosomal recessive disorders. Only a limited number of patients with these disorders have been described. We present a patient with a cobalamin metabolism defect in addition to a rather common microdeletion syndrome in order to demonstrate the complexity of pediatric genetic diagnosis when clinical features cannot be explained by a single etiology. As genetic syndromes such as 22q11.2 deletion syndrome are more commonly diagnosed, we may begin to diagnose more patients with multiple genetic disorders.
Observations Our patient was referred initially for evaluation of possible congenital Marfan syndrome. Physical examination revealed a hypotonic baby with long fingers and toes, protuberant ears, mild micrognathia, and lateral nasal bridge build-up. Clinical history was significant for atrial and ventricular heart defects, feeding difficulty, failure to thrive, anemia, and description of “atypical cherry red spots” on ophthalmology examination. The baby's biological mother also had a heart defect, long fingers, hypernasal speech, learning disabilities, and psychiatric problems. Though Marfan syndrome was a valid diagnostic consideration, physical exam and family history of our patient were more consistent with a diagnosis of 22q11.2 deletion syndrome which was confirmed by FISH. However, this diagnosis did not explain the findings on ophthalmology exam. Thus, a metabolic work-up was initiated. Laboratory tests for Tay Sachs disease and GM-1 gangliosidosis were normal. Further studies, however, revealed elevation in methylmalonic acid and homocysteine in the urine. These findings suggested a defect in cobalamin metabolism in addition to 22q11.2 deletion syndrome. The ophthalmology findings originally thought to be cherry red spots were reevaluated and later described as unusual macular reflexes. In review of the literature, some patients with cobalamin metabolism defects have had abnormal ophthalmology exams with macular changes.
Conclusions This case report illustrates the complex nature of diagnosis in a pediatric patient when specific features cannot be explained by one unifying etiology. The unexpected association of 22q11.2 deletion syndrome and defect in cobalamin metabolism noted in our patient may also prompt further investigation for gene identification in cobalamin metabolism defects.