RESUMO
Joubert syndrome is a clinically and genetically heterogeneous ciliopathy characterized by a typical cerebellar and brainstem malformation (the "molar tooth sign"), and variable multiorgan involvement. To date, 24 genes have been found mutated in Joubert syndrome, of which 13 also cause Meckel syndrome, a lethal ciliopathy with kidney, liver and skeletal involvement. Here we describe four patients with mild Joubert phenotypes who carry pathogenic mutations in either MKS1 or B9D1, two genes previously implicated only in Meckel syndrome.
Assuntos
Doenças Cerebelares/genética , Transtornos da Motilidade Ciliar/genética , Encefalocele/genética , Anormalidades do Olho/genética , Doenças Renais Císticas/genética , Mutação , Doenças Renais Policísticas/genética , Proteínas/genética , Retina/anormalidades , Anormalidades Múltiplas , Adulto , Doenças Cerebelares/patologia , Cerebelo/anormalidades , Criança , Pré-Escolar , Transtornos da Motilidade Ciliar/patologia , Proteínas do Citoesqueleto , Encefalocele/patologia , Anormalidades do Olho/patologia , Feminino , Humanos , Doenças Renais Císticas/patologia , Imageamento por Ressonância Magnética , Masculino , Doenças Renais Policísticas/patologia , Retina/patologia , Retinose Pigmentar , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Hyperglycemia is an exceptional manifestation of methylmalonic acidemia (MMA). We describe a patient with MMA in whom we observed a hyperglycemia which improved under treatment of the metabolic crisis. CASE REPORT: A 14 month-old boy presented with an acute generalized dystonia and lethargy preceded by fever, vomiting and lethargy at the age of 13 months. Biological investigations showed a hyperglycemia, a lactic acidosis and a hyperammonemia. Urinary organic acid analysis showed accumulation of methylmalonic acid, tiglylglycine and methylcitrate leading to the diagnosis of MMA. The patient underwent symptomatic treatment with rapid improvement of general condition, consciousness and gradual normalization of biological parameters especially glycemia after 6 days without using insulinotherapy. DISCUSSION: MMA is an autosomal recessive disorder caused by a deficiency of methylmalonyl-CoA mutase resulting in methylmalonic acid accumulation. Biochemically, the disorder is typically characterized by: metabolic acidosis, ketonemia or ketonuria, hyperammonemia, leukopenia, thrombocytopenia and anemia. Hypoglycemia is a frequent manifestation of MMA. Our patient presented a hyperglycemia, which is unusual in MMA, since we found only three patients reported with this association. Pathophysiology remains unknown. In reported cases, hyperglycemia was treated by insulin therapy and reducing glucose intravenous infusion, with fatal outcome. In our patient glycemia spontaneously normalized after treatment of the metabolic crisis. CONCLUSION: Hyperglycemia is an exceptional manifestation of MMA and could be a seriousness marker.