RESUMO
Hepatosplenomegaly is one of the cardinal signs of Hunter disease; however, portal hypertension has not been described. We report portal hypertension in an adult Hunter patient with the attenuated phenotype.
Assuntos
Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/genética , Adulto , Humanos , Fígado/patologia , Fenótipo , Baço/patologiaRESUMO
Pleuropulmonary blastoma (PPB) is a rare and aggressive primary intrathoracic neoplasma of children. The prognosis is extremely poor with frequent metastasis to the brain and bone. We present a 4-year-old girl with a tumor mass in the right hemithorax initially diagnosed as pneumoniae. Tumor resection was performed and the histologic report indicated the diagnosis of PPB. The patient received chemotherapy comprising vincristine, actinomycin D, doxorubicin, cisplatin, and cyclophosphamide. Irradiation was performed with total 45 Gy at the right lower pulmonary lobe. She relapsed 29 months later at the pleura between the right middle and lower pulmonary lobe. Tumor resection and total 45 Gy of irradiation were performed again. High-dose chemotherapy comprising cisplatin, adriamycin, and cyclophosphamide was performed followed by autologous peripheral blood stem cell transplantation (PBSCT). The patient achieved complete hematologic recovery. Thirty-one months after PBSCT, no signs of relapse have been observed. Although it might be that the patient could have been cured with second surgery alone or by the surgery and subsequent chemotherapy, high-dose chemotherapy and PBSCT should be considered for the treatment of relapsed PPB.
Assuntos
Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Transplante de Células-Tronco de Sangue Periférico , Blastoma Pulmonar/terapia , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Pré-Escolar , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Reações Falso-Positivas , Humanos , Neoplasias Pulmonares/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Pneumonia/diagnóstico , Pneumonia/patologia , Prognóstico , Blastoma Pulmonar/patologia , Transplante Autólogo , Vincristina/administração & dosagemRESUMO
We investigated mutations of the iduronate-2-sulfatase (I2S) gene and structural characteristics of I2S to clarify genotype/phenotype relationships in 18 Japanese patients with mucopolysaccharidosis type II. The I2S gene was analyzed in five patients with a severe phenotype and in 13 patients with an attenuated phenotype. The tertiary structural model of the human I2S was constructed by homology modeling using the arylsulfatase structure as a template. We identified four missense mutations and a nonsense mutation in the severe phenotype; four missense, two nonsense, three frame shifts, and one each of splice and amino acid deletion in the attenuated phenotype. Seven of them (L73del, Q75X, G140R, C171R, V401 fs, C422 fs, and H441 fs) were novel mutations. Structural analysis indicated that the residues of the mutations found in the severe phenotype would have direct interactions with the active site residues or should break the hydrophobic core domain of I2S, whereas residues of the missense mutations found in the attenuated phenotype were located in the peripheral region. In addition, effects by deletion or frameshift mutations could also be interpreted by the structure. Structural analysis of mutant proteins would help in understanding the genotype/phenotype relationships of Hunter disease.
Assuntos
Análise Mutacional de DNA , Iduronato Sulfatase/genética , Mucopolissacaridose II/genética , Mutação , Adolescente , Adulto , Processamento Alternativo , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Criança , Pré-Escolar , Códon sem Sentido , Mutação da Fase de Leitura , Humanos , Iduronato Sulfatase/química , Japão , Modelos Moleculares , Mutação de Sentido Incorreto , Estrutura Terciária de Proteína , Deleção de SequênciaRESUMO
Mucopolysaccharidosis IVA (MPS IVA), a progressive lysosomal storage disease, causes skeletal dysplasia through excessive storage of keratan sulfate (KS). We developed an ELISA-sandwich assay that used a MAb specific to KS. Forty-five blood and 59 urine specimens from MPS IVA patients (ages 1-65 y) were analyzed to determine whether KS concentration is a suitable marker for early diagnosis and longitudinal assessment of disease severity. Blood specimens were obtained from patients categorized as phenotypically severe (n = 36) and milder (n = 9). Urine specimens were also analyzed from patients categorized as severe (n = 56) and milder (n = 12), respectively. Blood KS levels (101-1525 ng/mL) in MPS IVA patients were two to eight times higher than those in age-matched controls (15-323 ng/mL). It was found that blood KS level varied with age and clinical severity. Blood KS levels in both MPS IVA and controls peaked between 5 and 10 y of age (mean, 776 versus 234 ng/mL, respectively). Blood levels in severe MPS IVA were 1.5 times higher than in the milder form. In contrast to blood, urine KS levels in both MPS IVA and controls peaked between 1 and 5 y (15.3 versus 0.26 mg/g creatinine), and thereafter declined with age. Urine KS level also varied with age and clinical severity, and the severe MPS IVA phenotype was associated with 6.7 times greater urine KS excretion than the milder one. These findings indicate that the new assay for blood or urine KS may be suitable for early diagnosis and longitudinal assessment of disease severity in MPS IVA.
