Enamel Defects in Methylmalonic Acidemia

BACKGROUND:  The hereditary methylmalonic acidemias (MMA) are a group of autosomal recessive enzymopathies that feature massive accumulation of methylmalonate and propionate-derived metabolites in the bodily fluids.  Most cases of isolated MMA are caused by mutations in methylmalonic-CoA mutase (MUT), a vitamin B₁₂-dependent enzyme that converts methylmalonyl-CoA into the Krebs cycle intermediate, succinyl-CoA.  Impaired metabolism of cobalamin (cbl) causes further types of MMAs.  While disorders are clinically and biochemically heterogeneous, many patients exhibit failure-to-thrive, strokes, kidney disease, pancreatitis, and early mortality.  Oral pathology has not been studies in these conditions.

OBJECTIVE:  To characterize dental features in MMA, and to correlate these findings with complementation status and serum MMA levels.

METHODS:  Thirty-one individuals with various types of MMA received clinical, radiographic, and photographic intraoral examination.  Anterior teeth of our study group were reviewed using the Developmental Defects of Enamel (DDE) Index and compared with review of thirty-seven controls (Table).

RESULTS:  One patient (cblC-type) presented with microdontic, cone shaped primary teeth.  Eleven of the thirty-one patients (35%) exhibited enamel defects of confluent opacities, lining, or pitting, significantly greater than the control group (Table).  DDE was significantly associated with the presence of permanent anterior teeth (OR=3.82, p=0.02).   No association was found between DDE and MMA type (9 MUT0, 5 cblC, 2 cblA, 1 cblB, and 3 unknown types).  A positive correlation was found between DDE and massively elevated serum MMA (r=0.56, p=0.001), a possible indication of renal failure.

CONCLUSION:  This is the first analysis of dental findings in patients with MMA and cbl disorders.  Renal dysfunction in children has been associated with enamel hypoplasia, and the enamel defects observed in the MMA patient group may be related to renal disease.  These enamel anomalies expands the phenotypic manifestations seen in MMA and suggests that dental development may be altered in these disorders.   

 

Table.  Developmental Defects of Enamel (DDE) are significantly greater * in the MMA group than in the controls.
	MMA Subjects	Controls	p value
n	31	33	-
Ages (range in years old, mean ± SEM)	2-34, 12.37 ± 1.53	5-33, 15.30 ± 1.14	0.21
F / M	20 / 11	18 / 15	0.45
DDE (mean ± SEM)	2.00 ± 0.46	0.91 ± 0.23	0.03 *