Genetics of Methylmalonic Acidemia Workup

Updated: Mar 16, 2015
  • Author: Brendan Lee, MD, PhD; Chief Editor: Maria Descartes, MD  more...
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Workup

Laboratory Studies

The reference ranges mentioned below may vary depending on the analytical method used.

Urine organic acids measured using gas chromatography–mass spectrometry (GC-MS) reveal large amounts of methylmalonic acid, methylcitrate, propionic acid, and 3-OH propionic acid.

Plasma amino acid measurements typically reveal elevated glycine levels. However, plasma glycine levels can also be within the reference range, even in an infant who previously had glycine levels outside of the reference range. The reference range is 100-390 mmol/L. Glycine may not be used as a metabolic marker.

Acylcarnitine profile (dry blood spot or plasma) reveals an elevation of propionylcarnitine (C3) levels and may reveal decreased free carnitine and total carnitine levels.

Total plasma homocysteine levels are assessed in cases of combined methylmalonic acidemia (MMA) and homocystinuria (cblC, cblD, and cblF forms of MMA). The reference range for all age groups is 2-14 mmol/L.

Plasma MMA levels are assayed for management. The reference range for all age groups is less than 0.2 mmol/L.

Plasma cobalamin levels are assessed, and the reference range is 130-785 pg/mL.

A CBC count is obtained to rule out macrocytic anemia, neutropenia, and thrombocytopenia.

Capillary blood gas is measured.

The reference range for ammonia levels in newborn infants is 90-150 mcg/dL. The reference range for infants aged 0-2 weeks is 79-130 mcg/dL. The reference range for those older than 1 month is 29-70 mcg/dL.

The reference range for blood glucose levels in full-term newborn infants is 45-120 mg/dL. The reference range for children is 60-105 mg/dL.

Plasma lactate is measured. The venous reference range is 5-20 mg/dL, and the arterial reference range is 5-14 mg/dL.

Electrolyte levels are also obtained.

Plasma uric acid levels are obtained. The reference range for those aged 0-2 years is 2.4-6.4 mg/dL. The reference range for children aged 2-12 years is 2.4-5.9 mg/dL.

The reference range for plasma creatinine for newborn infants is 0.6-1.2 mg/dL. The reference range for infants is 0.2-0.4 mg/dL, and the reference range for children is 0.3-0.7 mg/dL.

The reference range for plasma urea is 5-21 mg/dL.

The GFR is measured in older children, and the reference range for newborn infants is 40-65 mL/min/1.73 m2. The reference range for children older than 1 year is 98-150 mL/min/1.73 m2.

Prenatal diagnosis is possible by measuring activity of methylmalonyl-CoA mutase in cultured amniocytes.

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Imaging Studies

Brain CT scanning and MRI typically reveal involvement of basal ganglia and white matter.

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Other Tests

The advent of next-generation sequencing has given rise to panels of DNA tests that can test for many of the genes at once. These panels offer high sensitivity and specificity, although they may miss duplication or deletion of parts of a specific gene. Here, targeted array comparative hybridization with coverage of specific genes is used. Finally, clinical whole-exome sequencing may offer the potential to identify oligogenic causes and/or new genetic causes of MMA.

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