Wilson disease associated with immune thrombocytopenia: A case report and review of the literature

BACKGROUND Wilson disease (WD) is a genetic disorder of hepatic copper excretion,leading to copper accumulation in various tissues.The manifestations are quite variable,and hemolytic anemia is the most common hematological presentation.WD associated with thrombocytopenia is very rare.CASE SUMMARY We report the case of an 11-year-old Chinese girl with WD that was associated with immune thrombocytopenia (ITP).Thrombocytopenia was the initial chief complaint for her to visit a hematologist,and ITP was diagnosed based on the results of a bone marrow biopsy and positive antiplatelet autoantibodies.About two weeks before the thrombocytopenia was found,the patient developed drooling.Tremors developed in her right hand about one week after being diagnosed with ITP,after which she was admitted to our hospital.Further evaluations were performed.Ceruloplasmin was decreased,with an increased level of copper in her 24-h urine excretion.Kayser Fleischer's ring (K-F ring) was positive.The ultrasound showed liver cirrhosis,and brain magnetic resonance imaging showed that the lenticular nucleus,caudate nucleus,and brainstem presented a low signal intensity in T1-weighted images and high signal intensity in T2-weighted images.WD was diagnosed and a genetic analysis was performed.A compound heterozygous mutation in ATP7B was detected;c.2333G>T (p.Arg778Leu) in exon 8 and c.3809A>G (p.Asn1270Ser) in exon 18.The former was inherited from her father and the latter from her mother.However,her parents showed normal liver function and negative K-F rings.Such a compound mutation in a case of WD associated with ITP in children has not been published previously.CONCLUSION WD can associate with thrombocytopenia but the mechanism is still unclear.We recommend that antiplatelet autoantibodies should be tested in WD patients with thrombocytopenia in future to verify the association.

SATB2-associated syndrome caused by a novel SATB2 mutation in a Chinese boy:A case report and literature review

BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report a case of a 13-year-old Chinese boy with lifelong global developmental delay,speech and language delay,and intellectual disabilities.He had short stature and irregular dentition,but no other abnormal clinical findings.A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2,c.687C>A(p.Y229X)(NCBI reference sequence:NM_001172509.2),and neither of his parents had the mutation.This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics.SAS was diagnosed,and special education performed.Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease.The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures:(1)SATB2 haploinsufficiency;(2)the interference of truncated SATB2 protein to wild-type SATB2;and(3)different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.CONCLUSION Global developmental delays are usually the initial presentations,and the diagnosis was challenging before other presentations occurred.Regular follow-up and genetic analysis can help to diagnose SAS early.Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.