RESUMEN
BACKGROUND: In hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome, impaired ornithine transport across the mitochondrial membrane causes ornithine accumulation in cytoplasm. The resulting mitochondrial ornithine deficiency leads to reduced clearance of ammonia through the urea cycle. First described in 1969, no long-term follow-up has been reported. METHODS: Four patients were followed up for 11 to 38y. Diagnosis was made by plasma amino acid analysis using ion exchange chromatography, HPLC orotic acid measurement, and (14)C-ornithine incorporation study using cultured fibroblasts. DNA from fibroblasts was amplified and sequenced. Blood ammonia was controlled by restriction of protein intake. RESULTS: All patients had reduced (14)C-ornithine incorporation. Mutation analysis revealed two novel mutations in the ORNT1 gene. Neurologic outcome included memory loss, low IQ, tremor, spasticity of extremities, bladder incontinence, and abnormal gait. Neuroimaging revealed subcortical, cerebral and cerebellar atrophy, sparing the basal ganglia. Individual examination showed pyramidal signs, cerebellar signs, paraplegia, movement disorder, dystonia, and epilepsy. One patient had 3 pregnancies, one of which resulted in intrauterine growth retardation. CONCLUSIONS: Our patients expand the clinical phenotype of adults with HHH. Long-term follow-up showed serious neurologic outcomes in all patients; three patients clearly exhibited progression of neurologic dysfunction despite control of hyperammonemia. Intracellular ornithine deficiency may adversely affect brain functions.
Asunto(s)
Hiperamonemia/fisiopatología , Trastornos Innatos del Ciclo de la Urea/fisiopatología , Adulto , Sistemas de Transporte de Aminoácidos Básicos/genética , Aminoácidos/sangre , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hiperamonemia/sangre , Hiperamonemia/genética , Masculino , Persona de Mediana Edad , Proteínas de Transporte de Membrana Mitocondrial , Ornitina/sangre , Ornitina/deficiencia , Ornitina/genética , Fenotipo , Factores de Tiempo , Trastornos Innatos del Ciclo de la Urea/sangre , Trastornos Innatos del Ciclo de la Urea/genéticaRESUMEN
Cleidocranial dysplasia is a well-documented rare congenital disorder of the bone characterized by abnormalities of the skull, clavicle, and dentition. Despite numerous observations, there are still comparatively few reports regarding patients with cleidocranial dysplasia that focus on the impact of reconstruction of these defects on facial aesthetics. We report a 19-year-old woman with opened metopic and sagittal sutures and delayed closure of the anterior fontanelle. Through bicoronal incision and pericranial elevation, the defect was fully exposed. BoneSource was used to fill the cranial defect and was contoured to the desired cosmetic outcome. During a 24-month follow-up period, no absorption or recurrence was seen, and the patient was satisfied.
Asunto(s)
Sustitutos de Huesos/uso terapéutico , Displasia Cleidocraneal/cirugía , Frente/anomalías , Hueso Frontal/anomalías , Hidroxiapatitas/uso terapéutico , Procedimientos de Cirugía Plástica/métodos , Fontanelas Craneales/anomalías , Fontanelas Craneales/cirugía , Suturas Craneales/anomalías , Suturas Craneales/cirugía , Estética , Femenino , Estudios de Seguimiento , Frente/cirugía , Hueso Frontal/cirugía , Humanos , Hueso Parietal/anomalías , Hueso Parietal/cirugía , Satisfacción del Paciente , Resultado del Tratamiento , Adulto JovenRESUMEN
A patient with pericardial effusion and a complicated presentation of primary systemic carnitine deficiency (PSCD) is described. This is the first case of PSCD reported to have pericardial effusion. Compound heterozygosity for two mutations in the SLC22A5 gene, T440M and F23del, and four SLC22A5 polymorphisms (c.IVS3+6A>G, c.-77G>A, c.-78C>T, and p.S95S) were identified in the patient.