ABERRANT COBALAMIN METABOLISM WITH HOMOCYSTINURIA AND METHYMALONIC ACIDURIA

Abstract

Marked elevations in serum vitamin B₁₂ (2523 pg/ml) and total serum folate (60 ng/ml) were noted in a malnourished, hypotonic eight month old hispanic male with macrocytic anemia. A positive urine nitroprusside screen was followed by measurements of homocystine(HCy)(36.5μmol/d), elevated cystathionine (40.8μmol/d) and methylmalonic acid(MMA) (457 mg/d) in 24h urine collections.

This excretion of HCy and MMA suggested an aberration in vitamin B₁₂ handling since both pathways require cobalamin(Cbl) cofactors. Analysis of pretreatment serum by TLC and bioautography showed more than half the Cbl present migrated with the cyano-form(CN-Cbl), a marked reduction in the HCy cofactor(MeCbl) and a nearly normal percent of MMA cofactor(AdoCbl). Family screening studies did not reveal comparable levels of HCy or MMA. HCy loading indicated a delayed maternal methionine clearance.

A 90% reduction in 24h MMA excretion followed intramuscular hydroxocobalamin(OHCbl) but no consistent reduction in plasma or urine HCy was achieved on an unregulated diet. Anemia and macro-cytosis resolved as muscle tone, auditory responsiveness and nutritive sucking improved with alternate day OHCbl therapy.

Our patient is most like "Cbl-C" variants previously described with severe multi-system involvement. Early macrocytic anemia, elevated serum vitamin B₁₂, and a unique cobalamin pattern suggest a potential new variant in this metabolic pathway.

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