RESUMO
Deficiency of the IL-1 receptor antagonist (DIRA) is a recently described rare autoinflammatory disease, caused by loss of function mutations in IL1RN leading to the unopposed activation of the IL-1 pathway. We describe a novel nonsense mutation in the IL1RN gene, associated with early intrauterine onset, death and multiorgan involvement in a prematurely born baby. The protein prediction model indicated that the novel Q119X mutation would result in a nonfunctional protein by impairing the ability of the IL-1Ra to bind and antagonize signaling through the IL-1R. Since the disorder may mimic severe bacterial infections and the treatment with anakinra is life saving, we intend to raise awareness of the syndrome and the possibility of a founder mutation that may lead to the diagnosis of additional cases in Turkey. The clinical suspicion of DIRA is critical to avoid improper management of the patients with antibiotics alone and death from multiorgan failure.
Assuntos
Síndromes de Imunodeficiência/genética , Proteína Antagonista do Receptor de Interleucina 1/deficiência , Proteína Antagonista do Receptor de Interleucina 1/genética , Mutação/imunologia , Consanguinidade , Evolução Fatal , Feminino , Morte Fetal , Humanos , Síndromes de Imunodeficiência/imunologia , Recém-Nascido , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Interleucina-1alfa/imunologia , Interleucina-1alfa/metabolismo , Masculino , Modelos Moleculares , Receptores de Interleucina-1/imunologia , Receptores de Interleucina-1/metabolismo , Irmãos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , TurquiaRESUMO
Griscelli syndrome (GS) is a rare autosomal recessive disorder characterized by partial albinism. Three different types are caused by defects in three different genes. Patients with GS type 1 have primary central nervous system dysfunction, type 2 patients commonly develop hemophagocytic lymphohistiocytosis, and type 3 patients have only partial albinism. While hematopoietic stem cell transplantation is life saving in type 2, no specific therapy is required for types 1 and 3. Patients with GS types 1 and 3 are very rare. To date, only 2 patients with type 3 and about 20 GS type 1 patients, including the patients described as Elejalde syndrome, have been reported. The neurological deficits in Elejalde syndrome were reported as severe neurodevelopmental delay, seizures, hypotonia, and ophthalmological problems including nystagmus, diplopia, and retinal problems. However, none of these patients' clinical progresses were reported. We described here our two new type 1 and two type 3 patients along with the progresses of our previously diagnosed patients with GS types 1 and 3. Our previous patient with GS type I is alive at age 21 without any other problems except severe mental and motor retardation, patients with type 3 are healthy at ages 21 and 24 years having only pigmentary dilution; silvery gray hair, eye brows, and eyelashes. Since prognosis, treatment options, and genetic counseling markedly differ among different types, molecular characterization has utmost importance in GS.
Assuntos
Perda Auditiva Neurossensorial/genética , Piebaldismo/genética , Transtornos da Pigmentação/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab27 de Ligação ao GTPRESUMO
SCID affects T and B cell differentiation and functions, presenting with severe opportunistic infections in the early postnatal period. It is fatal unless stem cell transplantation is performed. RS SCID forms are caused by defects in the NHEJ pathway, the enzymatic process required for the repair of DNA double-strand breaks. Cernunnos-XLF defect is one of the defects in this pathway. Here, we present two patients with Cernunnos-XLF defect, both having microcephaly, prominent growth retardation, and T-B-NK+SCID, one of whom had AHA. These patients received hematopoietic stem cells from HLA identical related donor without conditioning regimen and recovered without any complication. Now, both of the patients are well and alive seven and one yr after transplantation, respectively. A remarkable observation was the severe diarrhea that occurred in both patients soon after transplantation.
Assuntos
Transplante de Medula Óssea , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/cirurgia , Enzimas Reparadoras do DNA/deficiência , Proteínas de Ligação a DNA/deficiência , Feminino , Marcadores Genéticos , Humanos , Lactente , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/metabolismoRESUMO
Partial or total CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain are among the autosomally inherited SCID presenting with T-B+NK+ phenotype with lymphopenia. The clinical findings are generally severe in all except for CD3 gamma deficiency. Here we present a 10-month-old CD3 gamma deficient boy with IBD. The patient had suffered from intractable diarrhea, recurrent pulmonary infections and oral moniliasis since two months of age. Following the first allogeneic HSCT from his HLA-identical (6/6) sister after a reduced intensity regimen, a second transplantation was performed five months later. On day +19 after second transplantation, the CD3 TCR alpha/beta chain expression increased to 66% with development of full donor chimerism (98.6%). A significant improvement in diarrhea, perianal lesions, and rectal fistula was observed suggesting an improvement in inflammatory bowel disease. The patient died at home on day +50 with a sudden respiratory failure secondary to an undetermined infection. The case was interesting being the first reported case with SCID and inflammatory bowel disease who responded very well to HSCT by full recovery of intractable diarrhea, failure to thrive, laboratory findings, and improvement of fistula formation.
