SIFD as a novel cause of severe fetal hydrops and neonatal anaemia with iron loading and marked extramedullary haemopoiesis

Abstract

<jats:p>SIFD describes a heritable, syndromic condition characterised principally by sideroblastic anaemia (SA) with immunodeficiency, fevers and developmental delay, arising in mutations within the TRNT1 gene. Other clinical manifestations of SIFD include cardiomyopathy, seizures, sensorineural hearing loss, renal dysfunction, metabolic abnormalities, hepatosplenomegaly and retinitis pigmentosa.</jats:p><jats:p>Presentation of SIFD is variable but typically in early childhood with SA or with fever. In this report, we extend the described SIFD phenotype. We describe a kindred in which the index case presented with fetal hydrops, and early neonatal death, and the second child had severe anaemia at delivery. Both cases had prominent extramedullary erythropoiesis and numerous circulating nucleated red blood cells.</jats:p>

Diseases Associated with Defects in tRNA CCA Addition

“…Given the increased availability of routine TREC measurement, the authors further propose to use this test as an early screening test for these clinically heterogeneous diseases. Barton et al described an unusual case of severe chronic antenatal anemia accompanied by extramedullary hematopoiesis, a high number of circulating nucleated red blood cells, and fetal hydrops resulting in an early neonatal death [41]. Bi-allelic mutations in TRNT1 (c.608+1G>T and c.668T>C) were confirmed in the affected individual suggesting that TRNT1 deficiency is the underlying cause of the disease.…”

Congenital sideroblastic anemia associated with B cell immunodeficiency, periodic fevers, and developmental delay: A case report and review of mucocutaneous features

“…1 Genotyping of individuals with SIFD revealed its association with an autosomal recessive mutation in the template-independent RNA polymerase tRNA nucleotidyl transferase 1 (TRNT1), which is required for the maturation of cytosolic and mitochondrial transfer RNAs (tRNAs). 2,3 So far, mucocutaneous involvement was described in two cases presenting in one as brittle hair and in other as chronic ichthyosis, punctuated with eruptions of erythema and/or hypopigmentation. Skin biopsy of ichthyotic skin revealed a perivascular lymphohistiocytic infiltrate within the papillary dermis but lacked specific diagnostic features; electron microscopy showed small foci of fibrillar amyloid-like material.…”

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

“…Muscle, liver and kidney biopsy: increased of enlarged mitochondria 14 [ 26 ] M Compound heterozygous: c.383A > G p.D128G Exon 4 Missense c.518A > T p.Y173F Exon 5 Missense 3.5 Y - - - - - - 3.5y ataxia, dysarthria, gross motor regression, hypotonia, ptosis, horizontal ophthalmoplegia. At 5 y and 8 m hypotonia, ptosis and horizontal ophthalmoplegia, speech slow and dysarthric Neuroimaging:abnormal signals in brainstem and dentate nucleus 15 [ 6 ] M Compound heterozygous c.126_128delAGA Exon 2 Deletion c.1246delA [ 6 ] Exon 8 Deletion 1y + - microcytosis with anisocytosis, normal value of hb, poikiocytosis with eliptocytes No Retinitis pigmentosa, diffuse outer retinal atrophy with foveal preservation Arthritis, JIA (first year of life) 16¥ [ 6 ] M Compound heterozygous: C.609-26 T > C Intron 5 Splicing c.1246A ins[ 8 ], p.S418fs Exon 8 Frameshift 21y - - Microcytosis and anysocytosis No Retinitis pigmentosa, mild pallor of optic nerve, macular oedema - 17¥ [ 6 ] M Compound heterozygous: C.609-26 T > C Intron 5 Splicing c.1246A ins[ ...…”