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Joana Regala1, Susana Gomes2, Graça Mira2; Rita Silva3; Ana Cristina Ferreira1; Sílvia Sequeira1

1 – Metabolic Unit, Paediatric Department, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central EPE, Lisbon
2 – Paediatric Department, Hospital do Espírito Santo de Évora, EPE, Évora
3 –Paediatric Neurology Service, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central EPE, Lisbon

IX Simpósio Internacional da Sociedade Portuguesa de Doenças Metabólicas, 21-22 Março de 2014, Coimbra
12th International Congress of Inborn Errors of Metabolism, 3rd-6th September 2013, Barcelona

Intracellular metabolism of cobalamin, comprehend eight different complementation groups, three of these affecting the common synthesis of both Methylcobalamin and Adenosylcobalamincofactors – cblC, cblD andcblF deficiencies. CblDdeficiency is the rarest, has no haematological abnormalities and can also present with isolated methylmalonicaciduria or homocystinuria due to different mutations on the MMADHC gene.

Case Report
A twenty-year-old gipsy girl was first admitted to the hospital (Badajoz) at 18 months for cyanosis and ocular revolution. Developmental delay and frequent vomiting were reported. Onneurological examination she had axialhypotonia, decreased visual contact, poor hand manipulation, absent language and unsteady gait.Metabolic investigation revealed methylmalonicaciduria (1330 mmol/molCr) and increased urinehomocysteine (261 µmol/gCr). Treatment with hydroxycobalamin, folate, betaine, metronidazol and carnitinewas startedwithimprovement of biochemical parameters and neurologicalabnormalities.
Complementation studies performed on cultured fibroblastssuggested a cblC/cblD deficiency. MMADHC sequencing detected homozigosity for c.748C>T mutation.
She had two further episodes of metabolic decompensation at 13 and 20 years, with ataxia, tremor, slurred speech and cognitive regression related to discontinuation of medication. Generalized tonic clonic seizures were present only in the first episode when EEG revealed frontal paroxystic activity.Presently, on physical examination she has minor facial dysmorphisms, slight mental retardation, nystagmus on extreme gaze positions and brisk tendon reflexes.Brain MRI is normal.

We describe this case as very few cases of CblD defects have been reported.It’s description may help in the recognition of apparent phenotype-genotype correlations and the association of mutations with specific ethnicities.

Keywords: cobalamin, cblD, case report