ABSTRACT
BACKGROUND: Immune thrombocytopenia (ITP) and Evans syndrome (ES) are manifestations of immune dysregulation. Genetic variants in immune-related genes have been identified in patients with ITP and especially ES. We aimed to explore familial autoimmunity in patients with ITP and ES to understand possible contributions to chronicity. PROCEDURE: We assessed family history in two ways: via patient report for ITP and ES and by population-based analysis using the Utah Population Database (UPDB) for ITP. A total of 266 patients with ITP and 21 patients with ES were identified via chart review, and 252 of the 266 patients with ITP were also identified in the UPDB. RESULTS: Chart review showed familial autoimmunity in 29/182 (15.9%) and 25/84 (29.8%) of patients with newly diagnosed+persistent (nd+p) ITP and chronic ITP (cITP), respectively, (p = .009). The UPDB analysis revealed that autoimmunity in relatives of patients with nd+pITP was higher than in relatives of controls (odds ratio [OR]: 1.69 [1.19-2.41], p = .004), but was not significantly increased in relatives of patients with cITP (OR 1.10 [0.63-1.92], p = .734). Incomplete family history in medical records likely contributed to the observed discrepancy. CONCLUSIONS: The findings suggest that familial autoimmunity may have a stronger association with the development of ITP rather than its duration. Twelve (57.1%) patients with ES reported autoimmunity in their relatives. UPDB analysis was omitted due to the small number of patients with ES. The use of population databases offers a unique opportunity to assess familial health and may provide clues about contributors to immune dysregulation features within families.
ABSTRACT
A transfusion-requiring "late anemia" can complicate the management of neonates convalescing from hemolytic disease of the fetus and newborn (HDFN). This anemia can occur in any neonate after HDFN but is particularly prominent in those who received intrauterine transfusions and/or double-volume exchange transfusions. Various reports describe this condition as occurring based on ongoing hemolysis, either due to passive transfer of alloantibody through breast milk or persistence of antibody not removed by exchange transfusion. However, other reports describe this condition as the result of inadequate erythrocyte production. Both hypotheses might have merit, because perhaps; (1) some cases are primarily due to continued hemolysis, (2) others are primarily hypoproductive, and (3) yet others result from a mixture of these two mechanisms. We propose prospective collaborative studies that will resolve this issue by serially quantifying end-tidal carbon monoxide. Doing this will better inform the assessment and treatment of neonates recovering from HDFN.
Subject(s)
Erythroblastosis, Fetal , Humans , Infant, Newborn , Erythroblastosis, Fetal/therapy , Female , Blood Transfusion, Intrauterine , Pregnancy , Hemolysis , Anemia, Neonatal/therapy , Exchange Transfusion, Whole Blood , Erythrocytes , ErythropoiesisABSTRACT
Severe congenital neutropenia (SCN) is a rare disorder, often due to pathogenic variants in genes such as ELANE, HAX1, and SBDS. SRP54 pathogenic variants are associated with SCN and Shwachman-Diamond-like syndrome. Thirty-eight patients with SRP54-related SCN are reported in the literature. We present an infant with SCN, without classic Shwachman-Diamond syndrome features, who presented with recurrent bacterial infections and an SRP54 (c.349_351del) pathogenic variant. Despite ongoing granulocyte colony-stimulating factor therapy, this patient has no evidence of malignant transformation. Here we establish a framework for the future development of universal guidelines to care for this patient population.
Subject(s)
Neutropenia , Infant , Humans , Virulence , Mutation , Neutropenia/genetics , Neutropenia/pathology , Congenital Bone Marrow Failure Syndromes/genetics , Shwachman-Diamond Syndrome , Signal Recognition Particle/genetics , Adaptor Proteins, Signal Transducing/geneticsABSTRACT
Hereditary fructose intolerance is a rare autosomal recessive metabolic disorder characterized by liver failure, renal tubulopathy, growth retardation, and occasionally death upon exposure to fructose. We present a 2-month-old male infant diagnosed with pyloric stenosis who developed disseminated intravascular coagulopathy following pyloromyotomy. Unexplained persistent coagulopathy, acute liver failure, and metabolic dysfunction led to whole-exome sequencing, which revealed compound heterozygous variants in ALDOB (p.Arg60Ter and p.Ala150Pro), diagnostic of hereditary fructose intolerance. Shortly after initiating a fructose-free diet, our patient had resolution of his coagulopathy, hepatic, and metabolic dysfunction.
Subject(s)
Fructose Intolerance , Pyloromyotomy , Diet , Fructose Intolerance/diagnosis , Humans , Infant , Liver , MaleSubject(s)
Anemia , Thrombocytopenia , Adolescent , Anemia/diagnosis , Anemia/etiology , Female , Humans , Thrombocytopenia/complications , Thrombocytopenia/diagnosisSubject(s)
Atypical Hemolytic Uremic Syndrome , Thrombotic Microangiopathies , Adolescent , Female , HumansABSTRACT
In North America, jaundiced neonates are not usually tested for G6PD deficiency if the family is of European ancestry. However, we describe such a family where ≥35 males have had severe (Class I) G6PD deficiency. Many of the jaundiced neonates did not have this diagnosis considered, at least three of whom developed bilirubin neurotoxicity. Over seven generations 35 affected males were identified. Three developed signs of kernicterus spectrum disorder; three had exchange transfusions for hyperbilirubinemia; and nine received one or more blood transfusions during childhood.
Subject(s)
Glucosephosphate Dehydrogenase Deficiency/genetics , Glucosephosphate Dehydrogenase/genetics , Polymorphism, Single Nucleotide , Female , Humans , Hyperbilirubinemia/genetics , Infant, Newborn , Kernicterus/genetics , Male , North America , Pedigree , White People/geneticsABSTRACT
We report a novel glucose-6-phosphate dehydrogenase (G6PD) variant (c.1375C>G) discovered in a 3-day-old Hispanic male child from Salt Lake City, UT, USA. This newborn presented with severe hyperbilirubinemia (29.8 mg/dL or 510 µmol/L) and marked hemolysis evidenced by elevated end-tidal carbon monoxide concentration (5.9 ppm, normal <1.7 ppm). Despite a very low prevalence of G6PD deficiency in Hispanic populations, we pursued testing for this condition and found he had low erythrocyte G6PD enzyme activity (2.8 U/g Hb, normal 9.9-16.6 U/g Hb) and a novel G6PD variant. His mother was heterozygous for this same variant, and she had a moderate decrease in G6PD enzyme activity (7.1 U/g Hb). On the basis of these findings, we propose this variant as a novel pathogenic mutation.
Subject(s)
Glucosephosphate Dehydrogenase Deficiency , Glucosephosphate Dehydrogenase , Hyperbilirubinemia , Female , Glucosephosphate Dehydrogenase/genetics , Glucosephosphate Dehydrogenase Deficiency/genetics , Heterozygote , Hispanic or Latino/genetics , Humans , Hyperbilirubinemia/genetics , Infant, Newborn , MaleABSTRACT
Dizygotic twin males, born at 34 weeks gestation, had prolonged jaundice, microcytic, hypochromic anemia, FABarts hemoglobin, elevated end-tidal CO, and blood films consistent with hereditary pyropoikilocytosis. DNA sequencing revealed both had a heterozygous alpha spectrin (SPTA1) mutation (c.460_462dup) inherited from their asymptomatic mother, plus a 3-base pair duplication in alpha globin (HBA2) (c.364_366dupGTG) inherited from their asymptomatic father.
Subject(s)
Anemia, Hemolytic/complications , Anemia, Hypochromic/complications , Elliptocytosis, Hereditary/complications , Jaundice/complications , Anemia, Hemolytic/blood , Anemia, Hemolytic/genetics , Anemia, Hypochromic/blood , Anemia, Hypochromic/genetics , Elliptocytosis, Hereditary/blood , Elliptocytosis, Hereditary/genetics , Humans , Infant, Newborn , Jaundice/blood , Jaundice/genetics , Male , Point Mutation , Spectrin/genetics , Twins, Dizygotic/geneticsABSTRACT
Infantile pyknocytosis is a rare, self-limited, hemolytic condition of unknown pathogenesis. It is diagnosed when a neonate with Coombs-negative hemolytic anemia has abundant pyknocytes and a characteristic clinical course after other hemolytic disorders has been excluded. Previous reports suggest that transfusions might be avoidable in this condition by administering recombinant erythropoietin. We cared for a patient with this disorder where we employed novel diagnostics and therapeutics. Despite these, and a good outcome free of transfusions, we continue to consider the condition to be idiopathic.
ABSTRACT
The congenital dyserythropoietic anemias are a heterogeneous group of disorders characterized by anemia and ineffective erythropoiesis. Congenital dyserythropoietic anemia type I (CDA1) can present in utero with hydrops fetalis, but more often it presents in childhood or adulthood with moderate macrocytic anemia, jaundice, and progressive iron-overload. CDA1 is inherited in an autosomal recessive manner, with biallelic pathogenic variants in CDAN1 or C15orf41. This case report documents a severe fetal presentation of CDA1 where we identified two novel compound heterozygous mutations in CDAN1 and describes the associated pathologic findings and levels of iron-regulatory proteins hepcidin, erythroferrone, and GDF15.