Prolonged thrombocytopenia in a child with severe neonatal alloimmune reaction and Noonan syndrome.

Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.

Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies.

The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.

["Benign" monoclonal gammopathy and chronic lymphatic leukemia in a patient with Noonan syndrome]. / "Benigne" monoklonale Gammopathie und chronisch lymphatische Leukämie bei einem Patienten mit Noonan-Syndrom.

HISTORY: At the age of 32 a "benign" monoclonal gammopathy of lightchain kappa with Bence Jones protein is diagnosed in a man born 1934. In addition a Noonan-syndrome is found. COURSE: Twenty-four years later he gradually develops a chronic lymphatic leukaemia (B-CLL) which up to now does not need treatment (October 1996). The neoplastic B-cells exprime monoclonal lightchain lambda on the cellmembrane and in the cytoplasma undetectable by immunefixation in the serum. Irrespective of that the known monoclonal gammopathy exprimes IgG-kappa without an increase in the number of plasmacells in the bonemarrow. CONCLUSION: There are hints that the congenital Noonan-syndrome can be associated with B-cell disorders.

Islet cell cytoplasmic antibodies (ICA) in diabetes and disorders of glucose tolerance.

Islet cell cytoplasmic antibodies were determined in 85 individuals 60 to 74 years old with fasting hyperglycaemia, in 65 patients with cystic fibrosis, in 113 patients with pancreatitis, in 21 patients with Turner's phenotype, and in 135 first-degree relatives of patients with Type 1 (insulin-dependent) diabetes. Islet cell antibodies were absent in all 60 to 74-year-old subjects with fasting hyperglycaemia detected by screening, and who did not require insulin treatment within 3 years. Islet cell antibodies were also absent in all patients with pancreatitis, cystic fibrosis, or Turner's phenotype. Islet cell antibodies were detected in 2 out of 135 (1.5%) first-degree relatives of new Type 1 diabetic patients, and in 1 out of 371 (0.3%) non-diabetic control subjects. During 12 years of follow-up 1 of the 2 first-degree relatives with islet cell antibodies and the only positive control developed Type 1 diabetes. It is suggested that islet cell antibodies are primarily associated with Type 1 diabetes and not with other disorders of glucose tolerance.

H-Y antigen in 46,XY gonadal dysgenesis.

Presence of H-Y antigen has been correlated with testicular differentiation, and absence of H-Y with failure of testicular differentiation, in a variety of mammalian species. To determine more precisely the relationship between expression of H-Y antigen and development of the testis, we studied the cells of phenotypic females with the 46,XY male karyotype. Blood leukocytes were typed H-Y+ in five XY females with gonadal dysgenesis, although in other studies blood leukocytes from XY females with gonadal dysgenesis were typed H-Y-. Thus mere presence of H-Y antigen is not sufficient to guarantee normal differentiation of the testis. In the present paper we review evidence for an additional factor in gonadal organogenesis, the H-Y antigen receptor. We infer that testicular development requires engagement of H-Y and its receptor. It follows that XY gonadal dysgenesis is the consequence of functional absence of the H-Y testis inducer as in the following conditions: failure of synthesis of H-Y or failure of specific binding of H-Y.

[Classical interstitial pneumonitis and mixed cryoglobulinemia in a male with Turner phenotype. Report of a case and review of the literature]. / Neumonitis intersticial clásica y crioglobulinemia mixta en un varón con fenotipo Turner. Reporte de 1 caso y revisión de la literatura.

We report a male patient, chromosomal complement 44 XY with Turner's phenotype, who has multiple skeletal, genitourinary and mild cardiac abnormalities, without hypogonadism. This patient developed a diffuse infiltrative pulmonary disease which result in pulmonary fibrosis, respiratory insufficiency and cardiac failure. He has also mixed cryoglobulinemia (Type III) with antigammaglobulin antibodies. The relationship among these problems and his phenotype is discussed. Apparently there is only a coincidental association.