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Clinical characteristics and treatment outcomes in Camurati-Engelmann disease: A case series.

ABSTRACT: Camurati-Engelmann disease is an extremely rare disease characterized by hyperostosis of multiple long bones. This condition is caused by heterozygous mutations in the TGFB1 gene.We describe the clinical and genetic characteristics of 4 Korean patients with this rare disease diagnosed at Asan Medical Center in Korea between June 2012 and May 2016, to increase awareness about this condition among general physicians and orthopedists. The presenting features, biochemical findings, radiographic and nuclear imaging findings, molecular analysis, and treatment outcomes of 4 patients were reviewed retrospectively.Two patients had sporadic disease, whereas the other 2 were familial cases. The average age at symptom onset was 8.8?±?5.5 (4-14) years. Symptoms included waddling gait or leg pain. Bone pain and easy fatigability were documented in all patients. Skeletal deformities such as osteoporosis, genu valgum, and severe scoliosis were observed. Visual and otologic manifestations presenting as exophthalmos, retinal detachment, and vestibulopathy were found in 3 patients. Skeletal survey showed diaphyseal expansion with diffuse cortical thickening of long bones in all patients. Bone scintigraphy images showed increased uptake of radioactive material in the calvarium and diaphysis of long bones. The mean erythrocyte sedimentation rate was 46.5?±?22.2 (20-72)?mm/h. Sequence analysis of TGFB1 revealed the previously reported mutations p.Arg218His, p.Arg218Cys, and p.Glu169Lys. Corticosteroid was effective in relieving pain, and losartan was used as maintenance therapy.Our experience suggests that this rare condition can be suspected in patients with characteristic symptoms and skeletal findings. Considering the presence of effective medical treatment, efforts are needed to identify more cases.

SUBMITTER: Kim YM

PROVIDER: S-EPMC5902284 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Clinical characteristics and treatment outcomes in Camurati-Engelmann disease: A case series.

Kim Yoon-Myung YM Kang Eungu E Choi Jin-Ho JH Kim Gu-Hwan GH Yoo Han-Wook HW Lee Beom Hee BH

Medicine 20180401 14

<h4>Background</h4>Camurati-Engelmann disease is an extremely rare disease characterized by hyperostosis of multiple long bones. This condition is caused by heterozygous mutations in the TGFB1 gene.<h4>Methods</h4>We describe the clinical and genetic characteristics of 4 Korean patients with this rare disease diagnosed at Asan Medical Center in Korea between June 2012 and May 2016, to increase awareness about this condition among general physicians and orthopedists. The presenting features, bioc ...[more]

PMID: 29620655

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Project description:BackgroundCamurati-Engelmann disease (CED) is a sclerosing bone dysplasia caused by transforming growth factor β1 (TGFB1) gene variants.ObjectiveWe aim to summarize the clinical characteristics and the efficacy of glucocorticoids in 14 individuals with CED, and explore the correlation between the phenotype and the SNP of rs1800470 (c.29C>T).MethodsClinical, biochemical, radiological, and therapeutic data were collected from 14 patients. DNA was extracted for TGFB1 variants detection by Sanger sequencing.ResultsThe median onset and record age were 3.0 and 16.1 years, respectively. All patients manifested bone pain and decreased subcutaneous fat tissue. Inflammatory markers increased in over 60% of patients, and the median erythrocyte sedimentation rate (ESR) was 1.40 (0.50~3.67) of the upper limit of normal (ULN), and the median high sensitivity C reactive protein (hsCRP) was 1.71 (0.48~12.56) of ULN. There was a positive correlation between ESR and hsCRP (rs=0.806, p=0.003). Both ESR and hsCRP were negatively correlated with the levels of hemoglobin (HGB), calcium, and creatinine, but positively correlated with the level of alkaline phosphatase. Four known variants of TGFB1 were identified, including p.Tyr171Cys, p.Arg218Cys, p.Arg218His, and p.Cys225Arg. Moreover, 35.7% and 28.6% of them carried the heterozygous and homozygous SNP of c.29C>T, called C/T and T/T groups, respectively, but 35.7% of them were without c.29C>T (C/C group). The onset age, anthropometric data, percentages of different clinical manifestations, and biochemical parameters were comparable among the three groups. But there were increasing trends in levels of HGB and calcium and decreasing trends in ESR and hsCRP among C/C, C/T, and T/T groups in turn. Glucocorticoid improves the two inflammatory markers among CED patients.ConclusionThe phenotype of CED is highly heterogeneous. There is no clear genotype-phenotype correlation, but it seems to have better trends of biochemical parameters in patients with CED carrying the T allele of rs1800470.

Project description:BackgroundCamurati-Engelmann disease (CED) is a rare genetic skeletal disorder characterized by limb pain, muscle emaciation and weakness, and cortical thickening of the diaphysis of long bones. It is caused by mutations in the transforming growth factor beta 1 (TGFB1) (type I) or other unknown gene(s) (type II). We present 8 consecutive patients with type I CED.MethodsWe retrospectively reviewed medical records and radiographs of type I CED patients with special reference to the mode of presentation, process of diagnostic work-up, and disease course. They were 4 sporadic patients, and two pairs of mother and son.ResultsWe categorized the mode of presentation into three groups. Group I had 4 patients who mainly presented with motor disturbances in young age. They drew medical attention for waddling gait, awkward ambulation or running, difficulty in going upstairs, or a positive Gower's sign at age 4 to 6 years. Subsequent development of limb pain and radiographic abnormality led to the diagnosis of CED at age 6 to 29 years. Group II had 3 patients who mainly presented with limb pain at age 15, 20, and 54 years, respectively. Radiographic evaluation and molecular genetic test led to the diagnosis of CED. The remaining 1 patient (group III) was asymptomatic until age 9 years when bony lesions at the tibiae were found incidentally. For the last 10 years, he intermittently complained of leg pain in the morning or after sports activities, which did not interfere with daily life. All the patients in group I showed a body mass index in the underweight range (< 18.4 kg/m2). At the latest follow-up, 4 patients in groups I and II required medication for the limb pain.ConclusionsCED presents with a wide range of severity. Awareness of this rare disease entity may be the key to timely correct diagnosis. This disease entity should be considered in the differential diagnosis of limb pain or motor disturbance in children to avoid unnecessary diagnostic work-up.

Project description:BackgroundCamurati-Engelmann disease (CED) is a rare bone dysplasia characterized by diffuse diaphyseal osteosclerosis. Skull base involvement in CED can result in hypopituitarism but is seldom reported. Our objective was to report a patient with acquired hypopituitarism due to CED and assess the management challenges.Case reportA 20-year-old boy presented with lower limb pain. He had walking difficulty in childhood, which was diagnosed as CED and managed with prednisolone. He later discontinued treatment and was lost to follow-up. Current re-evaluation showed short stature (-3.6 standard deviation), low weight (-4.3 standard deviation), and delayed puberty with delayed bone age (13 years). He was found to have secondary hypogonadism (luteinizing hormone level, 0.1 mIU/mL [1.7-8.6 mIU/mL]; follicle-stimulating hormone level, 1.0 mIU/mL [1.5-12.4 mIU/mL]; and testosterone level, 0.087 nmol/L [9-27 nmol/L]), growth hormone deficiency (low insulin-like growth factor I level, 120 ng/mL [226-903 ng/mL] and peak growth hormone level of 7 ng/mL on insulin-induced hypoglycemia), and secondary hypocortisolism (cortisol level, 105 nmol/L [170-550 nmol/L] and adrenocorticotropic hormone level, 6 pg/mL [5-65 pg/mL]). Serum prolactin level was normal (8.3 ng/mL [5-20 ng/mL]), and he was euthyroid on levothyroxine replacement. Magnetic resonance imaging revealed a partially empty sella. Sanger sequencing revealed a missense mutation (p.R218C/c.652C>T) in exon 4 of the TGFβ1 gene. The patient was treated with zoledronate, losartan, and oral prednisolone and continued on levothyroxine and testosterone replacement, which resulted in symptomatic improvement.DiscussionThe index case manifested severe CED requiring multimodality therapy. Later, he developed combined pituitary hormone deficiencies, which were managed with thyroid and gonadal hormone replacement with the continuation of glucocorticoids. The partial efficacy of bisphosphonates in CED has been reported in the literature.ConclusionSkull base involvement in CED can lead to structural and functional hypopituitarism as a result of intracranial hypertension.

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Clinical characteristics and treatment outcomes in Camurati-Engelmann disease: A case series.

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Clinical characteristics and treatment outcomes in Camurati-Engelmann disease: A case series.

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