RESUMEN
Angiotensin converting enzyme (ACE)-inhibitors decrease glomerular hyperfiltration but not microalbuminuria and proteinuria in glycogen storage disease type I. In the current study, we demonstrated that severe hyperlipidemia is associated with ACE-inhibitor ineffectiveness. We underline the importance of adequate metabolic control in glycogen storage disease type I. A combination therapy with ACE-inhibitors and lipid lowering drugs might be considered.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Predicción , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Hiperlipidemias/complicaciones , Hipolipemiantes/uso terapéutico , Enfermedades Renales/etiología , Lípidos/sangre , Adolescente , Adulto , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/efectos de los fármacos , Enfermedad del Almacenamiento de Glucógeno Tipo I/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo I/tratamiento farmacológico , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/tratamiento farmacológico , Incidencia , Italia/epidemiología , Enfermedades Renales/diagnóstico , Enfermedades Renales/epidemiología , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: To investigate the growth hormone (GH)-insulin-like growth factor (IGF) system in patients with glycogen storage disease type 1 (GSD1). STUDY DESIGN: This was a prospective, case-control study. Ten patients with GSD1a and 7 patients with GSD1b who were given dietary treatment and 34 sex-, age-, body mass index-, and pubertal stage-matched control subjects entered the study. Auxological parameters were correlated with circulating GH, either at basal or after growth hormone releasing hormone plus arginine test, insulin-like growth factors (IGF-I and IGF-II), and anti-pituitary antibodies (APA). RESULTS: Short stature was detected in 10.0% of patients with GSD1a, 42.9% of patients with GSD1b (P = .02), and none of the control subjects. Serum IGF-I levels were lower in patients with GSD1b (P = .0001). An impaired GH secretion was found in 40% of patients with GSD1a (P = .008), 57.1% of patients with GSD1b (P = .006), and none of the control subjects. Short stature was demonstrated in 3 of 4 patients with GSD1b and GH deficiency. The prevalence of APA was significantly higher in patients with GSD1b than in patients with GSD1a (P = .02) and control subjects (P = .03). The GH response to the provocative test inversely correlated with the presence of APA (P = .003). Compared with levels in control subjects, serum IGF-II and insulin levels were higher in both groups of patients, in whom IGF-II levels directly correlated with height SD scores (P = .003). CONCLUSION: Patients with GSD1a have an impaired GH secretion associated with reference range serum IGF-I levels and normal stature, whereas in patients with GSD1b, the impaired GH secretion, probably because of the presence of APA, was associated with reduced IGF-I levels and increased prevalence of short stature. The increased IGF-II levels, probably caused by increased insulin levels, in patients with GSD1 are presumably responsible for the improved growth pattern observed in patients receiving strict dietary treatment.
Asunto(s)
Estatura/fisiología , Enfermedad del Almacenamiento de Glucógeno Tipo I/sangre , Trastornos del Crecimiento/etiología , Hormona del Crecimiento/sangre , Somatomedinas/metabolismo , Adolescente , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo I/fisiopatología , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/fisiopatología , Humanos , Ensayo Inmunorradiométrico , Italia/epidemiología , Masculino , Prevalencia , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
L-2-hydroxyglutaric aciduria (L-2-HGA, MIM 236792) is a neurometabolic disorder caused by the toxic accumulation of high concentration of L-2-hydroxyglutaric acid in plasma and cerebrospinal fluid. Distinct mutations on the L2HGDH gene have been associated with the clinical and biochemical phenotype. Here we present three novel mutations (Gln197X, Gly211Val and c.540+1 G>A), which increase the present deleterious collection of L2HGDH gene up to 35 mutations that we have compiled in this study. In addition, we used the haplotypic information based on polymorphic markers to demonstrate the common origin of Gly57Arg harboring chromosomes.
Asunto(s)
Oxidorreductasas de Alcohol/genética , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/patología , Glutaratos/orina , Mutación , Adulto , Secuencia de Aminoácidos , Animales , Brasil , Niño , Preescolar , Femenino , Humanos , Italia , Masculino , Datos de Secuencia Molecular , PortugalRESUMEN
OBJECTIVE: To investigate the hypothalamus-pituitary-thyroid axis in patients with glycogen storage disease type 1(GSD1). STUDY DESIGN: Ten patients with GSD1a, 7 patients with GSD1b, and 34 sex- and age-matched healthy control subjects were enrolled in the study. RESULTS: The levels of serum-free thyroxine (FT4) were significantly lower in patients with GSD1a and GSD1b (P < .05), whereas thyrotropin was significantly higher compared with control subjects only in patients with GSD1b (P < .005). Thyroglobulin and thyroperoxidase auto-antibodies were significantly higher in patients with GSD1b than in patients with GSD1a and control subjects (P < .005). After thyrotropin-releasing hormone stimulation, an enhanced thyrotropin response was found in patients with GSD1a and patients with GSD1b (P < .005) compared with control subjects. The presence of a subclinical or overt hypothyroidism was found in 4 of 7 patients with GSD1b and in no patient with GSD1a (chi2 = 7.47, P < .005) or control subject (chi2 = 27.2, P < .0001). CONCLUSIONS: Patients with GSD1b have an increased prevalence of thyroid autoimmunity and hypothyroidism, although patients with GSD1a have little evidence of thyroid abnormalities. Concomitant damage at the level of the hypothalamus or pituitary gland might be hypothesized on the basis of the slightly elevated thyrotropin levels, even in patients with overt hypothyroidism.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo I/epidemiología , Hipotiroidismo/epidemiología , Tiroiditis Autoinmune/epidemiología , Adolescente , Adulto , Distribución por Edad , Estudios de Casos y Controles , Niño , Comorbilidad , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico , Humanos , Hipotiroidismo/diagnóstico , Masculino , Prevalencia , Probabilidad , Pronóstico , Estudios Prospectivos , Valores de Referencia , Medición de Riesgo , Distribución por Sexo , Estadísticas no Paramétricas , Pruebas de Función de la Tiroides , Tiroiditis Autoinmune/diagnóstico , Tirotropina/sangre , Tiroxina/sangreRESUMEN
We present a case of recurrent pulmonary alveolar proteinosis after heart-lung transplantation in a child with lysinuric protein intolerance. The recurrence of the pulmonary disease provides further insight regarding the possible pathogenesis of pulmonary alveolar proteinosis and therapeutic options for this complication.
Asunto(s)
Trastornos Innatos del Transporte de Aminoácidos/complicaciones , Trasplante de Corazón-Pulmón , Proteinosis Alveolar Pulmonar/complicaciones , Proteinosis Alveolar Pulmonar/cirugía , Trastornos Innatos del Transporte de Aminoácidos/orina , Resultado Fatal , Humanos , Lactante , Lisina/orina , Masculino , RecurrenciaRESUMEN
OBJECTIVE: To investigate brain morphology and function in patients with glycogen storage disease type I (GSDI). STUDY DESIGN: Nineteen patients (13 females and 6 males, aged 0.9-22.6 years) and 38 sex- and age-matched controls entered the study. Neurological examinations, psychometric tests (IQ, tests of performance and verbal abilities), standard electroencephalogram (EEG), somatosensory (SEPs), visual (VEPs), and brain-stem auditory evoked potentials (BAEPs), and brain magnetic resonance imaging (MRI) were performed. RESULTS: The results of tests of performance ability were lower in patients than in controls (P <.05). The prevalence of abnormal EEG findings (26.3% versus 2.6%), VEPs (38.4% versus 7.7%), SEPs (23.0% versus 0%), and BAEPs abnormalities (15.7% versus 0%) was higher in patients than in controls (P <.05). MRI pattern was altered in 57.1% of patients and was normal in all controls (P <.05). Both results of tests of performance ability and BAEPs abnormalities significantly correlated with the frequency of admissions for hypoglycemia, whereas EEG abnormalities correlated with dietary compliance (P <.05). CONCLUSIONS: Brain damage, probably caused by recurrent severe hypoglycemia, may be present in patients with GSDI.