Aciduria metilmalónica con homocistinuria de inicio neonatal: mejoría bioquímica y clínica con betaína

Urbón Artero, A.; Aldana Gómez, J.; Reig del Moral, C.; Nieto Conde, C.; Merinero Cortés, B.

doi:10.1016/S1695-4033(02)77813-2

Article information

La aciduria metilmalónica con homocistinuria es un infrecuente error del metabolismo celular de la cobalamina (cbl). Se describe la evolución bioquímica y el curso clínico de un paciente con la mutación cblC de comienzo neonatal.

Nacido tras una gestación normal, desarrolló una hipotonía general y graves dificultades de alimentación a los 5 días. El diagnóstico de aciduria metilmalónica con homocistinuria fue establecido basándose en los análisis de los aminoácidos y de los ácidos orgánicos, y confirmado mediante estudios enzimáticos y genéticos.

El paciente fue tratado inicialmente con hidroxicobalamina parenteral (1 mg diario), carnitina oral (100 mg/kg/ día) y dieta hipoproteica. Este tratamiento normalizó los niveles de ácido metilmalónico. A pesar del tratamiento con hidroxicobalamina parenteral, la disfunción neurológica, la hipotonía y el retraso del desarrollo no experimentaron ninguna mejoría. La suplementación con betaína oral (3 g diarios) desde el 3.° al 15.° mes produjo una disminución de la homocisteína total y de la homocistinuria. El paciente presentó mejoría clínicamente de su desarrollo neurológico y somatométrico.

Se concluye que el tratamiento precoz con betaína fue seguro y efectivo en nuestro paciente con aciduria metilmalónica con homocistinuria tipo cblC de inicio neonatal.

Palabras clave:

Aciduria metilmalónica

Homocistinuria

Homocisteína

Cobalamina

Betaína

Methylmalonic aciduria and homocystinuria is a very rare inborn error of cellular cobalamin (Cbl) metabolism.We describe the biochemical evolution and clinical course of a boy with neonatal onset CblC mutant defect.

Born after a normal pregnancy, the patient developed general hypotonia and severe feeding difficulties at 5 days of life. Diagnosis of methylmalonic aciduria and homocystinuria was established by amino-acid and organic acid analysis and was confirmed by enzyme and genetic studies.

The patient was initially treated with parenteral hydroxocobalamin (1 mg/day), oral carnitine (100 mg/kg/day) and a restricted protein diet. This treatment returned methylmalonic acid levels to normal. Despite the parenteral hydroxocobalamin therapy, the patient showed no improvement in neurological dysfunction, hypotonia or developmental delay. Oral betaine supplementation (3 g/day) from months 3-15 reduced plasma total homocysteine and homocystinuria. The patient showed clinical improvement in neurological and growth development.

We conclude that early betaine therapy was safe and effective in our patient with neonatal onset methylmalonic aciduria and homocystinuria type CblC.

Key words:

Methylmalonic aciduria

Homocystinuria

Homocysteine

Cobalamin

Betaine

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