1- Unidade de Doenças Metabólicas, Área Pediatria Médica, Hospital Dona Estefânia, CHLC
2- Serviço de Neuropediatria, Área Pediatria Médica, Hospital Dona Estefânia, CHLC
3- Radboud University Nijmegen Medical Center
- Poster no XI Simpósio Internacional da Sociedade Portuguesa de Doenças Metabólicas, Porto, 19 a 20 de Março de 2015
Introduction: MEGDEL syndrome (MIM #614739), is an autosomal recessive disorder of defective phospholipid remodelling first described in four patients with a distinct clinical phenotype. Patients presented with moderately elevated 3-Methyl- Glutaconic (3-MGA) aciduria, Deafness, Encephalopathy and neuro-radiological evidence of Leigh-like disease (MEGDEL association). Besides sensorial hearing loss other characteristics of this disorder may include hypoglycaemia, neonatal infections, bilateral optic nerve atrophy, microcephaly, and myoclonic epilepsy and features of defects of oxidative phosphorylation. Loss of function of mutations in the SERAC1 gene was related about two years ago.
Case Report: We describe a 5-year-old girl, born after an uneventful term pregnancy with IUGR, neonatal hypotonia, letargy and weak reflexes, transient hypoglycaemia and elevated transaminases in the neonatal period She has progressed with failure to thrive, severe delay of developmental milestones, axial hypotonia, spastic tetraparesis and dystonic movements. Investigations disclosed a pattern of metabolic acidosis with hyperlactacidaemia and high L/P ratio and the organic acids high levels mainly of 3-MGA. MRI performed at thirteen days of life suggests Leigh syndrome and a high lactate peak on spectroscopy. Muscle biopsy suggested mitochondrial disorder and the respiratory chain tests showed decreased activity of complexes II, IV, and II+III/CS. A leucine load test excluded a type I 3-MGA-uria defect. Over the time she showed persistent increase of 3MGA and 3-methylglytaric acid in the urine. Molecular studies of the SERAC1 gene revealed mutation c.310A>T and c.609+5_609+8del (splicing) confirming the diagnosis of MEGDEL syndrome.
Comments: Since MEGDEL syndrome was first described in 2006, an increasing number of patients have been related. Patients share 3-MGA-uria and mitochondrial
dysfunction. We believe this is the first Portuguese case of this syndrome. It is also an atypical case as Leigh syndrome is detected earlier than described in the literature and the patient has no hearing loss.
Palavras Chave: MEGDEL syndrome, 3-Methyl- Glutaconic