RESUMEN
Patients with Fanconi anemia (FA) are often perceived to have poor growth when general population growth curves are utilized. We hypothesize that FA patients have unique growth and aimed to create FA-specific growth charts. Height and weight data from ages 0 to 20 years were extracted from medical records of patients treated at the Fanconi Anemia Comprehensive Care Clinic at the University of Minnesota. Height, weight, and BMI growth curves were generated and fitted to reference percentiles using the Lambda-Mu-Sigma method. FA-specific percentiles were compared to WHO standards for ages 0-2 and CDC references for ages 2-20. In FA males, the 50th height- and weight-for-age percentiles overlap with the 3rd reference percentile. In FA females, only the 50th height-for-age percentile overlaps with the 3rd reference percentile. For weight, FA females show progressive growth failure between 6 and 24 months followed by stabilization around the 50th percentile. The FA BMI-for-age percentiles show similar patterns to the weight-for-age percentiles but have different timing of onset of adiposity rebound and broader variability in females. Growth in FA patients follows a different trajectory than available normative curves. FA-specific growth charts may be useful to better guide accurate growth expectations, evaluations, and treatment.
Asunto(s)
Estatura , Índice de Masa Corporal , Peso Corporal , Anemia de Fanconi , Gráficos de Crecimiento , Humanos , Femenino , Masculino , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/patología , Anemia de Fanconi/genética , Anemia de Fanconi/fisiopatología , Niño , Adolescente , Preescolar , Lactante , Adulto Joven , Recién NacidoRESUMEN
This article presents the haematopoietic stem cell transplantation (SCT) results of the complete Dutch Fanconi anaemia (FA) patient cohort. Sixty-eight Dutch FA patients have been transplanted since 1972. In total, 63 (93%) patients engrafted, 54 after first SCT and 9 after second SCT. Fludarabine (FLU)-based conditioning was associated with decreased graft failure (odds ratio 0·21, P = 0·01), decreased early mortality (hazard ratio 0·25, P = 0·01) and improved 5-year overall survival (FLU 87·8% [standard error (SE) 5·1%] versus non-FLU 59·3% [SE 9·5%], P = 0·01). Late mortality was mainly caused by squamous cell carcinoma. Twenty-two patients were treated with the current Dutch FA conditioning regimen (FLU 150 mg/m(2) and cyclophosphamide 30 mg/kg ± anti-thymocyte globulin - no irradiation). Stem cell donors were matched related (n = 8) or alternative donors (n = 14). Stable engraftment after first SCT was achieved in 19 (86%) patients. At a median follow-up of 3·9 years 20 (91%) patients are alive. Our study provides a unique overview of a nation-wide SCT cohort illustrating the major improvements in treatment regimen and patient outcome in recent years. It shows that a non-irradiation and busulfan-free conditioning regimen can be used successfully, also in alternative donor SCT. Furthermore, it underlines the importance of late cancer screening and comprehensive care for this complex disorder.
Asunto(s)
Anemia de Fanconi/epidemiología , Anemia de Fanconi/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Niño , Preescolar , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/mortalidad , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Estimación de Kaplan-Meier , Masculino , Mortalidad , Países Bajos/epidemiología , Oportunidad Relativa , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
CONTEXT: Endocrine problems are common in patients with Fanconi anemia (FA). About 80% of children and adults with FA have at least one endocrine abnormality, including short stature, GH deficiency, abnormal glucose or insulin metabolism, dyslipidemia, hypothyroidism, pubertal delay, hypogonadism, or impaired fertility. The goal of this report is to provide an overview of endocrine abnormalities and guidelines for routine screening and treatment to allow early diagnosis and timely intervention. EVIDENCE ACQUISITION: This work is based on a comprehensive literature review, including relevant articles published between 1971 and 2014, and proceedings of a Consensus Conference held by the Fanconi Anemia Research Fund in 2013. EVIDENCE SYNTHESIS: The panel of experts collected published evidence and discussed its relevance to reflect current information about the endocrine care of children and adults with FA before the Consensus Conference and through subsequent deliberations that led to the consensus. CONCLUSIONS: Individuals with FA should be routinely screened for endocrine abnormalities, including evaluation of growth; glucose, insulin, and lipid metabolism; thyroid function; puberty; gonadal function; and bone mineral metabolism. Inclusion of an endocrinologist as part of the multidisciplinary patient care team is key to providing comprehensive care for patients with FA.
Asunto(s)
Enfermedades del Sistema Endocrino/diagnóstico , Enfermedades del Sistema Endocrino/terapia , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/terapia , Tamizaje Masivo/normas , Guías de Práctica Clínica como Asunto , Adulto , Niño , Enfermedades del Sistema Endocrino/etiología , Anemia de Fanconi/complicaciones , Trastornos del Metabolismo de la Glucosa/diagnóstico , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/terapia , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/terapia , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Desnutrición/diagnóstico , Desnutrición/etiología , Desnutrición/terapia , Tamizaje Masivo/métodos , Delgadez/diagnóstico , Delgadez/etiología , Delgadez/terapiaRESUMEN
Features suggestive of Bartter syndrome (hypokalemia, hypochloremic metabolic alkalosis, and normal blood pressure despite hyperreninemia and hyperaldosteronism) were found in a 5-year-old black child with cystinosis and Fanconi syndrome. Review of his medical records revealed that these abnormalities had probably been present when he first became clinically ill at 2 years of age. Sodium and potassium chloride supplementation lead to improved growth and strength, partial correction of his electrolyte abnormalities, and a decrease in markedly elevated plasma renin activity. Literature review disclosed a similar presentation in four Caucasian children with cystinosis. Biochemical findings compatible with Bartter syndrome can occur together with evidence of generalized proximal renal tubular dysfunction (Fanconi syndrome) in nephropathic cystinosis.