ABSTRACT
La espondiloencondrodisplasia con desregulación inmune relacionada a ACP5 (SPENCDI #607944, por la sigla de spondyloenchondrodysplasia with immune dysregulation y el número que le corresponde en OMIM, Online Mendelian Inheritance in Man) es una displasia inmuno-ósea poco frecuente con manifestaciones heterogéneas y gravedad variable. Presenta lesiones espondilometafisarias, disfunción inmune y compromiso neurológico. Se reportan aspectos clínicos, radiológicos y genéticos de cuatro niñas con SPENCDI en un hospital pediátrico. Todas presentaron manifestaciones esqueléticas y tres de ellas enfermedad inmunológica grave. Se encontró en tres pacientes la variante probablemente patogénica c.791T>A; p.Met264Lys en homocigosis, y en una paciente las variantes c.791T>A; p.Met264Lys y c.632T>C; p.lle211Thr (variante de significado incierto con predicción patogénica según algoritmos bioinformáticos) en heterocigosis compuesta en ACP5. La presencia de la variante repetida c.791T>A sugiere la posibilidad de un ancestro en común en nuestra población. El reconocimiento y diagnóstico de esta entidad es importante para lograr un oportuno abordaje, que deberá ser multidisciplinario, orientado hacia la prevención de posibles complicaciones.
Spondyloenchondrodysplasia with immune dysregulation related to ACP5 (SPENCDI, OMIM number 607944) is an uncommon immune-skeletal dysplasia with heterogeneous manifestations and variable severity. It is characterized by spondylar and metaphyseal lesions, immune dysfunction, and neurological involvement. Here we report the clinical, radiological and genetic aspects of 4 girls with SPENCDI treated at a children's hospital. They all had skeletal manifestations and 3 developed severe immune disease. In 3 patients, the likely pathogenic variant c.791T>A; p.Met264Lys (homozygous mutation) was observed, while 1 patient had variants c.791T>A; p.Met264Lys and c.632T>C; p.lle211Thr (variant of uncertain significance with pathogenic prediction based on bioinformatics algorithms) caused by a compound heterozygous mutation in ACP5. The repeated presence of variant c.791T>A suggests the possibility of a common ancestor in our population. The recognition and diagnosis of this disorder is important to achieve a timely approach, which should be multidisciplinary and aimed at preventing possible complications.
Subject(s)
Humans , Female , Child, Preschool , Child , Autoimmune Diseases , Immunologic Deficiency Syndromes/complications , Tartrate-Resistant Acid Phosphatase/geneticsABSTRACT
Objective:To summarize the clinical features and gene phenotype of children with spondyloenchondrodysplasia with immune dysregulation (SPENCDI) caused by ACP5 gene mutation. Methods:The medical data and genetic phenotype of a child diagnosed with SPENCDI in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University in February 23, 2017 were analyzed retrospectively.Besides, " spondyloenchondrodysplasia" were taken as the search terms to perform the retrieval in CNKI, Wanfang Data, and PubMed, in an attempt to conduct the literature review.χ 2 test was used to compare the factors among children with different mutations. Results:The 4.5-year-old girl was admitted to hospital for complaint of " fever and chilblain-like rash" when she was 2 years old.She was diagnosed with systemic lupus erythematosus (SLE) concomitant with lupus nephritis.Methylprednisolone combined with cyclophosphamide, mycophenolate mofetil was used for the treatment.However, she experienced multiple infections, thrombocytopenia, limp, and growth retardation during the treatment.Genetic detection identified ACP5 gene compound hybrid mutation: c.779C>A and c. 770T>C.She was diagnosed with SPENCDI, and was subjected to follow-up.A total of 78 SPENCDI patients were retrieved from the databases, with various clinical manifestations of SPENCDI, commonly with skeletal involvement and immune phenotypes; 73.08% of the cases were positive for antinuclear antibodies, 57.69% of cases were positive for anti-double stranded-DNA antibodies and 34.62% of cases had neurological symptoms.In 58 cases, ACP5 gene mutations were detected, including 44 homozygous mutations and 14 compound heterozygous mutations.Patients with ACP5 gene homozygous mutation had a higher probability of consanguineous marriage in parents [56.82% (25/44 cases) vs.14.29% (2/14 cases)]; patients with ACP5 gene heterozygous mutation were more likely to develop SLE [64.29% (9/14 cases) vs.34.09% (15/44 cases)]( χ2=7.722, 3.992; all P<0.05). Conclusions:The majority of the ACP5 gene mutations are homozygous mutations in patients with SPENCDI, and heterozygous mutations are rare.The clinical manifestations of SPENCDI are various and complex, it is prone to develop autoimmune diseases, and there was no clear correlation between clinical features and gene phenotype in SPENCDI patients.