A 4-month-old patient was admitted to our hospital together with his twin brother due to a persistent thrombocytopenia complicated with muosal bleeding and skin petechiae. Both twins presented with thrombocytopenia on 1st day of life with normal findings on the initial physical examination.

At the age of 10 months, our patient developed a severe neurological deterioration, characterized by pronounced hypotonia, high-pitch cry, rapid visual and hearing decline and decreased level of consciousness. MRI of the brain revealed confluent symetrical signal changes of demyelinization and dysmyelination in the subcortical and deep white mater of both hemispheres. These findings were suggested the possibility of acute disseminated encephalomyelitis (ADEM) and further investigation was performed. Blood analysis proved CMV infection, with confirmed seroconversion at later time. During the following few months, his neurological status gradually improved, with regaining of the head and posture control. However, the right sided hemiparesis continued to persist.

Analysis of serum immunoglobulins revealed increase of IgE. Cellular imunodefficiency was found since our patient had decreased lymphocyte proliferation on phytohaemaglutinine (PHA) while proliferative response of cell cultures stimulated with concavaline A (conA) remained negative. Further investigation showed Coombs positive tests in several episodes of hemolytic anemia, with positive antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA). He also developed a chronic generalised molluscum contagiosum infection starting from the age of 18 months.

Due to a cellular immuno-defficiency, increase of the IgE antibodies, opportunistic infections as well as male gender and autoimmune disease manifestations, we suspected WAS. Genetic analysis for the detection of a mutation of WAS gene was performed in the patient at the age of 2 years, and subsequently in the patient’s mother, by polymerase chain reaction-single strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing of the PCR products. PCR-SSCP analysis in the exon 2 of the WAS gene disclosed aberrantly migrating bands in the patient and his mother. In the direct sequencing analysis of the PCR products for SSCP, a nucleotide substitution 190 T>C in the exon 2 was observed in the patient. Direct sequencing performed in the patient’s mother confirmed that she is a heterozygous carrier of the same mutation; thus, X-linked recessive inheritance was shown. Genetic status of mother’s parents and relatives is unknown.

Our patient was referred for hematopoetic cell transplantation.

Wiskott-Aldrich syndrome is an X-linked recessive condition that exhibits a wide spectrum of clinical severity [6]. Patients may develop mild thrombo-cytopenia or suffer more severe disorders from the spectrum. Autoimmune disorders are frequent, being present in 40% of large cohort of families [7]. In addition, malignant tumors can occur during childhood, but are more frequent in adolescents and young adults with the classic form of disorder [8]. Thus, the clinical diagnosis can be difficult and is usually supported by the detection of WAS gene mutations [9]. Our patient with mutation of WAS gene did not exhibit characteristic microthrombo-cytopenia, but increased platelet volume. Presence of macrothrombocytopenia in our patient could be due to the presence of autoimmune disorder. Causes of macrothrombocytopenia could also be immune trombocytopenic purpura (ITP) usually due to infection, drugs, vaccination and other causes. Rare hereditary causes of macrotrombocytopenia such as Bernard–Soulier syndrome, DiGeorge/Velocardiofacial syndrome or Platelet-type von Willebrand disease were ruled out based on clinical and laboratory findings.

In addition, he did not develop eczema or malignancies. Such clinical course was pointing out other possible diagnoses, such as congenital CMV infection resulting in delayed diagnosis. We stress the need for multidisciplinary assessment of patients with congenital or early infantile thrombocytopenia, including testing for mutations of the WAS gene in all unexplained cases even in the absence of characteristic microthrombocytopenia.

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