Prenatal diagnosis and therapy for a patient with vitamin B₁₂‐responsive methylmalonic acidaemia

Abstract

The prenatal therapy is described of a patient with vitamin B12-responsive methylmalonic acidaemia during the last 10 days of gestation with oral administration of vitamin B12 (20 mg/day) given to a mother did not normalize her urinary excretion of methylmalonic acid (MMA), which was 14.5 mmol/mol creatinine at 32 weeks of gestation. Before delivery, the mother was excreting 18.9 +/- 3.3 mmol MMA/mol creatinine (mean value at 7 days after vitamin B12 therapy), as well as at 32-37 weeks of gestation with no therapy. After birth, the level of MMA in the infant's urine was remarkably elevated (500-700 mmol/mol creatinine); the level of MMA in maternal urine decreased dramatically after delivery. Compared with two previous reports, the length of administration was not sufficient to reduce maternal MMA excretion. In future, the length of the therapy, route of administration and total dose of vitamin B12 to maintain an efficient level of vitamin B12 in an affected fetus should be considered.

Haplotype‐based noninvasive prenatal diagnosis of methylmalonic acidemia and the discovery of a recurrent pathogenic haplotype associated with c.609G>A

“…MMA is a treatable and preventable genetic metabolic disorder. Studies have shown that prenatal high‐dose VB12 intrauterine therapy can enhance the prognosis of MMA patients 30 . In addition, postpartum low‐protein diets, mecobalamin, or L‐carnitine can effectively prevent or mitigate neurological damage 31 .…”

“…Studies have shown that prenatal high-dose VB12 intrauterine therapy can enhance the prognosis of MMA patients. 30 In addition, postpartum low-protein diets, mecobalamin, or L-carnitine can effectively prevent or mitigate neurological damage. 31 Hence, early diagnosis and intervention are vital for MMA patients.…”

Prenatal pharmacotherapy for fetal anomalies: a 2011 update

“…Case reports of maternal treatment with oral or intramuscular vitamin B12 for prenatal treatment of fetal methylmalonic acidemia (MMA) date as far back as 1975 (Ampola et al ., 1975; van der Meer et al ., 1990; Soda et al ., 1995; Zass et al ., 1995; Spada et al ., 1999; Huemer et al ., 2005; Zhang et al ., 2008). MMA can present prenatally as growth restriction or dilated cardiomyopathy (De Bie et al ., 2009), or postnatally with recurrent vomiting, failure to thrive, developmental retardation, and hepatomegaly.…”

“…However, prenatal treatment is not always accompanied by improvements in biochemical markers of disease severity or the prevention of postnatal complications. This highlights the lack of knowledge regarding optimum dosing (Soda et al ., 1995) and the influence of fetal treatment on long-term outcomes (Huemer et al ., 2005). Monitoring the efficacy of prenatal treatment by measurement of odd-numbered fatty acid accumulation in newborn adipose tissue has been attempted, but its correlation with the prevention of neuropathology is unknown (Zass et al ., 1995).…”