ABSTRACT
In this report we describe different forms of clinical presentation of an autosomal dominant hypophosphatemic rickets (ADHR) in 4 members of the same family as well as the treatment used in these patients and their response to it. Patient No 1: a 60 year old female who consulted for bone pain: Bone densitometry showed osteoporosis. Laboratory assays showed hypophosphatemia with low renal phosphate threshold, high total alkaline phosphatase, normal intact PTH and normal serum calcium. With neutral phosphate and calcitriol, the biochemical parameters normalized and bone densitometry improved significantly in less than a year. Patient No 2 her grand daughter consulted at 1 year and 8 months of age for growth retardation (height at percentile 3) and genu varum. Laboratory assays showed low serum phosphate and high total alkaline phosphatase; thickening and irregular epiphyseal borders of the wrists were observed radiologically. She began treatment with calcitriol and phosphorus with normalization of laboratory parameters and increase in growth (height increasing to percentile 50 after 20 months of therapy). Patient No 3: mother of patient No 2, she had no clinical manifestations and normal densitometry but presented low serum phosphate (1.9 mg/dl) that normalized with neutral phosphate therapy. Patient No 4: he was the youngest son of Patient No 1, who had had hypophosphatemic rickets, by age 5; his serum phosphate normalized without treatment At age 29, he presented normal serum phosphate and bone densitometry. Genomic DNA analysis performed in patient No 3, showed missense mutation with substitution of arginine at position 179 for glutamine. The family was catalogued as having autosomal dominant hypophosphatemic rickets/osteomalacia.
Describimos distintas formas de presentación clínica de un raquitismo hipofosfatémico autosómicodominante en 4 miembros de una misma familia y su respuesta al tratamiento. Paciente N° 1: de sexofemenino de 60 años que consultó por dolores costales y pélvicos, con osteoporosis densitométrica, hipofosfatemia con bajo umbral renal de fósforo, PTH intacta normal y calcemia normal. Tratada con fósforo neutro y calcitriol logró la normalización bioquímica y una notable mejoría de la densitometría en menos de un año. Paciente N° 2: su nieta, consultó al año y ocho meses de edad por presentar talla en percentil 3 y genu varum. En el laboratorio mostró hipofosfatemia y fosfatasa alcalina total muy elevada y en la Rx de mano, ensanchamiento y deflecamiento epifisario compatible con raquitismo. Tratada con fósforo neutro y calcitriol, normalizó los parámetros bioquímicos y logró un ascenso en el percentil de talla de 3 a 50 a los 20 meses de tratamiento. Paciente N° 3: la madre de la paciente N° 2, quien sin ninguna manifestación clínica y con densitometría ósea normal presentó hipofosfatemia que se normalizócon tratamiento con fosfato neutro. Paciente N° 4: el tío de la paciente N° 2, tuvo raquitismo hipofosfatémico de niño,y luego de los 5 años normalizó el fósforo sin tratamiento. Estudiado a los 29 años presentó fósforo normal y densitometría ósea normal. El análisis del ADN genómico de la paciente N° 3 mostró una mutación con sentido erróneo en el gen del factor de crecimiento fifroblástico 23 (sustitución de arginina por una glutamina en posición 179). Por lo tanto se llegó al diagnóstico de raquitismo/osteomalacia hipofosfatémico autosómico dominante.
Subject(s)
Child , Female , Humans , Infant , Male , Middle Aged , Adult , Fibroblast Growth Factors/genetics , Hypophosphatemia, Familial/genetics , Mutation , Rickets/genetics , Alkaline Phosphatase/blood , Phosphates/therapeutic use , Hypophosphatemia, Familial/diagnosis , Hypophosphatemia, Familial/drug therapy , Osteomalacia/complications , Osteomalacia/diagnosis , Osteomalacia/genetics , Pedigree , Rickets/complications , Rickets/diagnosisABSTRACT
El raquitismo hipofosfatémico es una alteración metabólica transmitida genéticamente (ligada al cromosoma X) en donde disminuye la reabsorción de fosfato en el túbulo proximal. Esta enfermedad se manifiesta con defectos en la mineralización de los tejidos esquelético y dentario. El caso clínico presentado en este artículo corresponde a un niño de 8 años de edad con eta alteración en la que se observan deformidades en las extremidades inferiores (piernas arqueadas), disminución de su talla y bucalmente en los tejidos blandos, se aprecia gingivitis generalizada y sondajes periodontales no mayores de 2 mm. En el aspecto dentario existe una relación molar en clase II de Angle, con pérdida prematura de los molares temporales y por consecuencia, erupción prematura de los premolares permanentes. Debido a la asociación con la deficiente formación dentaria y la historia familiar, podríamos suponer una asociación entre raquitismo hipofosfatémico y las periodontitis de inicio precoz
Subject(s)
Humans , Male , Child , Hypophosphatemia, Familial/complications , Hypophosphatemia, Familial/diagnosis , Jaw Diseases/etiology , Tooth Abnormalities/etiology , Musculoskeletal Abnormalities/etiology , Musculoskeletal Abnormalities/genetics , Chile , Limb Deformities, Congenital/etiology , Limb Deformities, Congenital/genetics , Hypophosphatasia/diagnosis , Hypophosphatasia/etiology , Malocclusion, Angle Class II/etiology , Patient Care Team , Tooth Loss/etiologyABSTRACT
O raquitismo hipofosfatêmico dominante ligado ao cromossomo X é a forma mais comum de raquitismo familial, e caracteriza-se por hipo-fosfatemia associada a hiperfosfatúria e metabolismo anormal da vitamina D. Existem outras formas de hiperfosfatúrias hereditárias, sugerindo um complexo processo de homeostase do fosfato. Como não está definida qual a lesão básica do distúrbio, torna-se difícil o esclarecimento da fisiopatologia. Recentemente, através da abordagem de clonagem posicional, foi identificado um forte gene candidato, o PEX, que seria o responsável pelo distúrbio. Diversos tipos de mutações no PEX foram encontradas em cerca de 60 famílias. Os recentes avanços genéticos no estudo dessa doença muito têm contribuído para melhorar o entendimento da sua fisiopatologia e do controle do equilíbrio do fosfato.
Subject(s)
Humans , Adolescent , Adult , Middle Aged , Hypophosphatemia, Familial/physiopathology , Hypophosphatemia, Familial/diagnosis , Hypophosphatemia, Familial/genetics , Molecular Biology , Vitamin D/metabolismABSTRACT
Hypophosphatemic rickets (HR) has generated a lot of interest in recent times. There is need to recognize this disorder and differentiate it from the more common nutritional rickets because the therapy is different. It is also important to emphasize that a detailed clinical examination with pedigree analysis and easily available biochemical tests are adequate to establish the diagnosis in most cases. This report presents three families with hypophosphatemic rickets. Interestingly, many of these patients had a mixed picture of HR and nutritional rickets. Their important features are described with special emphasis on early initiation of treatment with oral phosphate and stringent monitoring of renal functions to prevent development of irreversible renal insufficiency.
Subject(s)
Adolescent , Adult , Child, Preschool , Female , Humans , Hypophosphatemia, Familial/diagnosis , Male , PedigreeABSTRACT
Nutritional rickets is caused by vitamin D deficiency due to lack of exposure to sunlight. Neonatal rickets occurs only in infants born to mothers with very severe osteomalacia. Calcium deficiency alone does not cause mineralisation defects. It only causes osteoporosis and secondary hyperparathyroidism with raised plasma, 1,25 (OH)2D and osteocalcin. Low 25-OHD, increased IPTH, increased alkaline phosphatase in plasma and decreased calcium and increased hydroxyproline in urine are diagnostic of rickets. Low or undetectable plasma levels of 25-OHD, in presence of high plasma 1,25(OH)2D and IPTH are often observed during treatment with vitamin D. Even the marginal intakes of fluoride (> 2.5 mg/day) cause rickets in calcium deficient children. Indian children often need high dose of vitamin D due to severely depleted D stores, high IPTH and severe bone disease (radiologic and histomorphometric) for treatment.
Subject(s)
Calcium, Dietary/administration & dosage , Child , Child, Preschool , Diagnosis, Differential , Female , Fluorides/administration & dosage , Humans , Hypophosphatemia, Familial/diagnosis , Infant , Infant, Newborn , Male , Rickets/drug therapy , Risk Factors , Vitamin D/administration & dosage , Vitamin D Deficiency/diagnosisABSTRACT
Um caso de raquitismo de início tardio, ocorrido em uma menina de 11 anos de idade, é apresentado. Os diagnósticos diferenciais säo discutidos. Na pesquisa etiológica, foi insistentemente procurado algum tumor que pudesse estar produzindo substância com efeito semelhante ao do paratormônio. É sugerido que a manifestaçäo seja secundária a um dos tipos de raquitismo hipofosfatêmico familiar, com apresentaçäo tardia, já que foi encontrada fosfatemia diminuída na mäe da paciente. A evoluçäo terapêutica foi excelente com o uso de calciferol e soluçäo neutra de fosfato.
Subject(s)
Humans , Female , Child , Ergocalciferols/therapeutic use , Hypophosphatemia, Familial/diagnosis , Phosphates/therapeutic use , Rickets/diagnosis , Diagnosis, Differential , Follow-Up Studies , Hypophosphatemia, Familial/drug therapyABSTRACT
Se analizan 14 pacientes con diagnóstico de raquitismo hipofosfatémico familiar controlados en el Servicio de Nutrición del Hospital General del Centro Médico "La Raza" del IMSS. Se describen las manifestaciones clínicas y la edad de inicio y de diágnostico, así como los exámenes de laboratorio y gabinete. Se comparó la respuesta clínica y de laboratorio al tratamiento inicial que recibieron a base de vitamina D2 y fosfatos, con la obtenida posteriormente con tratamiento con calcitriol y fosfatos, sin que se encontrara diferencias estadísticamente significativa. Se analizaron los antecedentes familiares en los pacientes, así como los resultados de laboratorio en 26 familiares, con lo cual se apoyó la etiología hereditaria del padecimiento. Así mismo, se hacen consideraciones sobre la etiopatogenia y el tratamiento del padecimiento
Subject(s)
Infant , Child, Preschool , Child , Humans , Male , Female , Alkaline Phosphatase/blood , Calcitriol/therapeutic use , Ergocalciferols/therapeutic use , Hypophosphatemia, Familial/diagnosis , Hypophosphatemia, Familial/physiopathology , Hypophosphatemia, Familial/therapy , Phosphates/blood , Phosphates/urine , Weight by HeightSubject(s)
Humans , Biopsy , Diagnosis, Differential , Bone Diseases/diagnosis , Bone Resorption/diagnosis , Osteogenesis/physiology , Osteomalacia/diagnosis , Chronic Kidney Disease-Mineral and Bone Disorder/diagnosis , Biopsy/instrumentation , Biopsy/standards , Hypercalcemia/diagnosis , Hypophosphatemia, Familial/diagnosis , Bone Demineralization, Pathologic/diagnosis , Bone Demineralization, Pathologic/physiopathology , Bone Resorption , Bone Resorption/pathologyABSTRACT
Os autores apresentam um caso de raquitismo vitamina D dependente do tipo II e discutem a etiopatogenia, os aspectos clínicos, laboratoriais, radiológicos e terapêuticos. O diagnóstico diferencial com raquitismo carencial e raquitismo vitamina D dependente tipo I é abordado