Case Report: Expanding Clinical, Immunological and Genetic Findings in Sideroblastic Anemia With Immunodeficiency, Fevers and Development Delay (SIFD) Syndrome

Abstract

Since the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. B-cell deficiency is a hallmark of SIFD syndrome, and multiple others immunological defects have been reported, but not high levels of double negative T cells. Here we report a Brazilian patient with a novel phenotype of SFID syndrome, carrying multiple immune defects and harboring a novel mutation on TRNT1 gene.

Clinical and Therapeutic Aspects of Sideroblastic Anaemia with B-Cell Immunodeficiency, Periodic Fever and Developmental Delay (SIFD) Syndrome: a Systematic Review

“…Since he started Etanercept good control of fever episodes 54 [ 24 ] Homozygous mutation c.914A > T, p.Asp305Val Exon 7 Missense 6 m Immunoglobulin replacement Alive at 14 years olds. Stopped Immunoglobulin replacement at 12 years old 55 [ 25 ] Compound Heterozygous c.495_498del, p.F167Tfs * 9 Exon 5 Frameshift c.1246A > G, p.K416E Exon 8 Missense 6 m RBC transfusions Immunoglobulin replacement Etanerceot Alive at 4 years with resolution of the main manifestations 56 [ 27 ] Compound heterozygous: c.498_501delATTT.Phe167fs,Exon5 Frameshift c.947C > T p.Ala316Val; Exon 7 Missense 2 m Immunoglobulin replacement Alive at 7 years old 57 [ 28 ] Compound heterozygous: c.407 C > G, p.Ala136Lys Exon 4 Missense c.361 G > A; p.Glu121Lys Exon 4 Missense 1 m Immunoglobulin replacement Corticosteroids Etanercept Alive 58 [ 29 ] Heterozygous NA Immunoglobulin replacement Anakinra Colchicine Anakinra failure Partial response to Colchicine …”

“…Immunologic abnormalities were documented in 48/58 (82.75%) patients, all showing an impairment in number of B-cell or circulating Immunoglobulin levels [ 1 – 5 , 7 – 25 , 27 , 28 ]. Extensive investigation of B-cell subsets highlighted an early defect in B-cell maturation with a block in the pre-B-II stage [ 1 , 20 ].…”

“…Moreover, Wiseman et al evaluated a progressive decline in T and NK cells seen in several cases of their cohort [ 1 ]. High expression of double-negative T cells in the peripheral blood has been reported in 2 patients by Giannaleou et al [ 28 ]. Furthermore Lougaris et al demonstrated in their patient a severe decrease in T cell receptor excision circles (TRECs) and Kappa-deleting recombination excision circles (KRECs) [ 16 ].…”

“…Neurological manifestations are reported in 48/58 (82.75%) patients with a widely variable phenotypic spectrum [ 1 – 5 , 7 – 12 , 14 – 18 , 21 – 23 , 26 , 28 ] (Table 1 ). The most frequent manifestations are developmental delay or progressive regression in 41 patients, cerebellar symptoms in 15/45 and partial or complex seizures in 15/45 [ 1 – 5 , 7 – 12 , 14 – 18 , 21 , 22 , 26 ].…”

“…Skin abnormalities were reported in 29/58 SIFD population (49%) mainly brittle hair or ichthyotic skin, panniculitis, erythema nodosum, morfea and aspecific rash [ 1 – 5 , 7 , 9 , 11 – 14 , 17 – 19 , 21 – 25 , 27 – 29 ]. A biopsy of erythematous nodule lesions showed a lobular and septal neutrophilic panniculitis [ 13 , 18 , 25 , 28 ]. Jfri’s adult patient (40 years old) showed lichen sclerosus and atrophicus and morphea [ 19 ].…”