Defect of Cobalamin Intracellular Metabolism Presenting as Diabetic Ketoacidosis: A Rare Manifestation

Abstract

Hypoglycemia is the usual feature of commonly occurring organic acidemias. Organic acidemias manifesting as hyperglycemia or diabetic ketoacidosis are rare and only a few cases have been reported. We report a 13-monthold boy who presented with vomiting, dehydration, coma, hyperglycemia, high anion gap metabolic acidosis and ketosis, mimicking diabetic ketoacidosis (DKA). Treatment with parenteral fluid, electrolytes, and insulin infusion resulted in an improvement in hyperglycemia, but persistence of metabolic acidosis and lack of improvement of neurologic status led us to suspect an organic acidemia. Urinary organic acid analysis revealed increased methylmalonic acid levels. In addition, hyperhomocysteinemia and homocystinuria were also noted in presence of normal vitamin B 12 levels. This confirmed the diagnosis of cobalamin metabolism defect leading to combined methylmalonic aciduria and homocystinuria. There was some improvement in neurologic status and metabolic parameters after treatment with low-protein diet, vitamin B 12 , folic acid, and L-carnitine, but he ultimately succumbed to polymicrobial nosocomial sepsis. The entire MMACHC gene of the patient was sequenced and no mutations were identified. This is probably the first case report of cobalamin intracellular metabolism defect (CblC/CblD/ CblF/CblJ or ABCD4) presenting as diabetic ketoacidosis.

Metabolic pathways at the crossroads of diabetes and inborn errors

“…While T2DM and IEMs may not have obvious genetic overlap, they certainly have phenotypic overlap. There have been case reports of IEMs “masquerading as” or “mimicking” diabetes, particularly for methymalonic acidura (Abramowicz et al, 1994; Boeckx and Hicks, 1982; Dejkhamron et al, 2016; Guven et al, 2012; Sharda et al, 2013). Scheuner et al mined the OMIM database and identified 37 Mendelian disorders for which adult-onset diabetes was a phenotypic component observed in two or more families (Scheuner et al, 2004).…”

Methylmalonic acidemia and diabetic ketoacidosis: An unusual association

“…Sharda et al . [ 10 ] reported a 13-month-old boy who presented with vomiting, dehydration, coma, hyperglycemia, high anion gap metabolic acidosis (HAGMA) and ketosis. He was treated in line of DKA with parenteral fluid, electrolytes, and insulin infusion that resulted in an improvement in hyperglycemia, but the persistence of HAGMA and lack of improvement of neurologic status.…”

“…So, DKA is an exceptional manifestation of MMA and could be a marker of poor prognosis. [ 9 10 11 ] The unusual presentation of MMA as DKA reminds us of the wide clinical spectrum of inborn errors of metabolism. In very young patients, who present with DKA and on being treatment with fluid and insulin show rapid improvement in hyperglycemia and/or poor response in metabolic acidosis or neurological status should be worked up for organic acidemia in particular MMA.…”