Enfermedad de Caffey después del primer año de vida: caso clínico / Caffey disease after the first year of life: clinical case

Objetivo: La enfermedad de Caffey o hiperostosis cor- tical infantil es una enfermedad rara que afecta uno o más huesos en los primeros meses de vida y debido a su baja inci- dencia está subdiagnosticada, y por tanto se aplican procedi- mientos invasivos innecesarios en su estudio y tratamiento. Se presenta un caso clínico atípico de enfermedad de Caffey en una paciente mayor de 1 año de edad y su resolución. Caso clínico: El servicio de Cirugía Maxilofacial del Hospital Provincial Pediátrico Eduardo Agramonte Piña de Camagüey, Cuba, atiende a una niña de 1 año y 10 meses que se encontraba hospitalizada por presentar una inflamación alarmante en la región facial y cervical precedida de un cua- dro febril y dificultad para alimentarse. Se indicaron los estu- dios apropiados, cuyos resultados, junto a las características clínicas, permitieron diagnosticar la enfermedad de Caffey. Aunque sea una enfermedad rara, es importante estudiarla para realizar un correcto análisis de cada caso y diferenciarla de otras enfermedades que requieren de conductas terapéuti- cas agresivas (AU)

Aim: Caffey's disease or infantile cortical hyperostosis is a rare disease that affects one or more bones in the first months of life and due to its low incidence, it is underdiag- nosed, and therefore unnecessary invasive procedures are applied in its study and treatment. An atypical clinical case of Caffey's disease in a patient older than 1 year and its reso- lution is presented. Case report: The Maxillofacial Surgery service of the Eduardo Agramonte Piña Provincial Pediatric Hospital in Camagüey, Cuba, takes the case of a 1 year and 10-month-old female patient who was hospitalized for an alarming inflam- mation in the facial and cervical region, preceded by a fever and difficulty to eat. The appropriate studies were indicated, which results, together with the clinical characteristics, al- lowed the diagnosis of Caffey's disease. Although it is a rare entity, it is important to study it to carry out a correct analysis of each case and differentiate it from other diseases that re- quire aggressive therapeutic behaviors (AU)

A novel FGF23 mutation in hyperphosphatemic familial tumoral calcinosis and its deleterious effect on protein O-glycosylation.

Background: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and ectopic calcification, predominantly at periarticular locations. This study was performed to characterize the clinical profile of tumoral calcinosis and to identify gene mutations associated with HFTC and elucidated its pathogenic role. Methods: The three subjects (two male and one female) were aged 30, 25 and 15 years, respectively. The clinical features, histopathological findings, and outcomes of three subjects with HFTC were retrospectively reviewed. The three subjects were analyzed for FGF23, GALNT3 and KL mutations. Function of mutant gene was analyzed by western blotting and wheat germ agglutinin affinity chromatography. Results: All subjects had hyperphosphatemia and elevated calcium-phosphorus product. Calcinosis positions included the left shoulder, left index finger, and right hip. Bone and joint damage were present in two cases and multiple foci influenced body growth in one case. The histopathological features were firm, rubbery masses comprising multiple nodules of calcified material bordered by the proliferation of mononuclear or multinuclear macrophages, osteoclastic-like giant cells, fibroblasts, and chronic inflammatory cells. The novel mutation c.484A>G (p.N162D) in exon 3 of FGF23 was identified in one subject and his family members. Measurement of circulating FGF23 in the subject confirmed low intact FGF23 and increased C-terminal fragment. In vitro experiments showed that the mutant FGF23 proteins had defective O-glycosylation and impaired protein proteolysis protection. Conclusion: We identified a novel FGF23 missense mutation, and confirmed its damaging role in FGF23 protein O-glycosylation. Our findings expand the current spectrum of FGF23 variations that influence phosphorus metabolism.

Use of Teriparatide in Hyperphosphatemic Familial Tumor Calcinosis: Evaluating the Interaction Between FGF23 and PTH on the Phosphaturic Effect.

Hyperphosphatemic familial tumor calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and calcium and phosphorus crystal deposition. It occurs due to the loss of function of FGF23. Herein, we report a case of a 50-year-old woman diagnosed with HFTC (homozygous variant in the GALNT3 gene, c.803_804 C insertion) with a history of ectopic calcifications in the past 30 years. Laboratory tests on admission were as follows: phosphate (P) 7.1 mg/dL (Normal range (NR) 2.5-4.5 mg/dL), FGF23 c-terminal 2050 RU/mL (NR < 150 RU/mL), and intact FGF23 (iFGF23) 18.93 pg/mL (NR 12.0-69.0 pg/mL). Treatment with acetazolamide, sevelamer, and a phosphorus-restricted diet was started, but phosphatemia remained high and calcifications continued to progress. In an attempt to further decrease P, a 36-day cycle of teriparatide (TPTD) 20 mcg twice daily was added, decreasing P from 6.2 to 5.2 mg/dL and increasing the 1.25(OH)2 vitamin D by 34.2%. As urinalysis was not feasible at the end of the 36-day cycle, a second cycle was performed for another 28 days, producing a similar decrease in P (from 6.4 to 5.5 mg/mL) and an evident decrease in the rate of tubular reabsorption of P (from 97.2 to 85.3%), however, accompanied by a worrying increase in calciuria. The use of TPTD 20 mcg twice daily in a patient with genetic resistance to FGF23 (HFTC) was associated with consistent increase in phosphaturia and reduction in phosphatemia, in addition to an increase in calcitriol. The resulting hypercalciuria precludes the therapeutic use of TPTD in HFTC and suggests an important role of FGF23, not only in phosphate homeostasis but also in avoiding any excess of calcitriol.

A probable case of infantile cortical hyperostosis in 2nd-4th centuries AD Romania.

OBJECTIVE: This study aims to discuss the differential diagnosis for the pathological alterations displayed on an infant skeleton from Romania. MATERIALS: One infant skeleton retrieved form the bathhouse of an abandoned Roman fort and dated between the 2nd and the 4th centuries AD. METHODS: All available skeletal elements were analyzed macroscopically. In addition, the isotopic signatures (δ13C and δ15N) and the control region of the human mitochondrial genome for this archaeological sample were analyzed. RESULTS: Based on dental development and long bone length, the skeleton was aged between birth and 2 months of age. Pathological lesions were noted on the mandible and diaphyses of long bones, but spared the metaphyses. CONCLUSIONS: The perinatal age of the individual, along with lesion morphology and location, suggests a diagnosis of infantile cortical hyperostosis. LIMITATIONS: The analysis would benefit from further stable isotope and mitochondrial genome analyses, which was limited due to the absence of comparative human and faunal remains from the site. SUGGESTIONS FOR FURTHER RESEARCH: Further multidisciplinary research on human archaeological remains from Romania would provide a clearer image of past disease and life histories in this geographic area.

[Osteopetrosis (Albers-Schoenberg disease). III. Current nosographic aspects and relations to other condensing osteopathies]. / L'osteopetrosi (malattia di Albers-Schönberg) Nota III. - Aspetti nosografici attuali e rapporti con altre osteopatie condensanti

A malignant paediatric variety and an adult variety of Albers-Schönberg disease are normally distinguished. On the basis of recent findings and personal observation it would appear advisable to accept two different courses of Albers-Schönberg disease in adults: one resembling the malignant infant form and the other with slow, practically asymptomatic (apart, obviously, from the skeletal lesions) course allowing for prolonged survival. This classification is of considerable practical importance for prognosis and therapeutic purposes. Other hereditary-familial and constitutional condensing osteopathy pictures exist that present radiological stigmata similar to those seen in Albers-Schönberg disease. The interest of the relations between A-S disease and certain of these condensing osteopathic conditions is obvious.