Exome sequencing detected an extremely rare case of foetal onset familial haemophagocytic lymphohistiocytosis type 5 presenting with hydrops foetalis

Thadchanamoorthy, Vijayakumary; Jayatunga, M T R; Dayasiri, Kavinda; Jasinge, Eresha; Jinnah, M L M; Pereira, Catarina; Skrahina, Volha; Thirukumar, M.

doi:10.1186/s12920-021-00897-z

Cited by 3 publications

(4 citation statements)

References 15 publications

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“…Studies were excluded if they did not discuss nHLH ( n = 280); aggregated nHLH patient data with all ages ( n = 83); provided insufficient detail and/or data describing a case of nHLH ( n = 28); and for other reasons ( n = 8). Two‐hundred‐five cases of nHLH from 142 articles were included in our analysis 12–152 …”

Section: Resultsmentioning

confidence: 99%

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

Kranz,

Hahn,

Thompson

et al. 2024

Pediatric Blood & Cancer

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BackgroundNeonatal hemophagocytic lymphohistiocytosis (nHLH), defined as HLH that presents in the first month of life, is clinically devastating. There have been few large descriptive studies of nHLH.ObjectivesThe objective of this study was to perform a meta‐analysis of published cases of nHLH.MethodsA comprehensive literature database search was performed. Cases of HLH were eligible for inclusion if clinical analysis was performed at age ≤30 days. Up to 70 variables were extracted from each case.ResultsA total of 544 studies were assessed for eligibility, and 205 cases of nHLH from 142 articles were included. The median age of symptom onset was day of life 3 (interquartile range [IQR]: 0–11, n = 141). Median age at diagnosis was day of life 15 (IQR: 6–27, n = 87). Causes of HLH included familial HLH (48%, n = 99/205), infection (26%, n = 53/205), unknown (17%, n = 35/205), macrophage activation syndrome/rheumatologic (2.9%, n = 4/205), primary immune deficiency (2.0%, n = 5/205), inborn errors of metabolism (2.4%, n = 5/205), and malignancy (2.0%, n = 4/205). Fever was absent in 19% (n = 28/147) of all neonates and 39% (n = 15/38) of preterm neonates. Bicytopenia was absent in 26% (n = 47/183) of patients. Central nervous system (CNS) manifestations were reported in 63% of cases (n = 64/102). Liver injury (68%, n = 91/134) and/or liver failure (24%, n = 32/134) were common. Flow cytometry was performed in 22% (n = 45/205) of cases. Many patients (63%, n = 121/193) died within the period of reporting. Discernable values for HLH diagnostic criteria were reported between 30% and 83% of the time.ConclusionsEvaluation of nHLH requires rapid testing for a wide range of differential diagnoses. HLH diagnostic criteria such as fever and bicytopenia may not occur as frequently in the neonatal population as in older pediatric populations. Neurologic and hepatic manifestations frequently occur in the neonatal population. Current reports of nHLH suggest a high mortality rate. Future publications containing data on nHLH should improve reporting quality by reporting all clinically relevant data.

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Section: Resultsmentioning

confidence: 99%

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

Kranz,

Hahn,

Thompson

et al. 2024

Pediatric Blood & Cancer

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“…168 Genetically confirmed cases with fatal outcomes have been implicated in PRF1 (familial HLH2) 169,170 and STXBP2 (familial HLH5). 171 In a 5-year-old with X-linked lymphoproliferative disease (XIAP) with dysregulated inflammasome activity, ALF and bone marrow failure was successfully treated by liver and bone marrow transplantation. 172 In a study looking at 30 children <24 months of age with ALF of indeterminate aetiology, 9 (30%) were found to have biallelic and 10 (33.3%) monoallelic variants in familial HLH genes including PFR1, UNC13D, RAB27A and LRBA although the pathogenicity of some of the reported variants were uncertain.…”

Section: Disorders Of Immune Regulationmentioning

confidence: 99%

“…Presentation is usually within 2 years of birth, including the neonatal period where infants are born in poor condition with hydrops fetalis 168 . Genetically confirmed cases with fatal outcomes have been implicated in PRF1 (familial HLH2) 169,170 and STXBP2 (familial HLH5) 171 . In a 5‐year‐old with X‐linked lymphoproliferative disease ( XIAP ) with dysregulated inflammasome activity, ALF and bone marrow failure was successfully treated by liver and bone marrow transplantation 172 .…”

Section: Disorders Of Immune Regulationmentioning

confidence: 99%

Genetic aetiologies of acute liver failure

Hegarty,

Thompson

2024

J of Inher Metab Disea

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Acute liver failure (ALF) is a rare, rapidly evolving, clinical syndrome with devastating consequences where definitive treatment is by emergency liver transplantation. Establishing a diagnosis can be challenging and, historically, the cause of ALF was unidentified in up to half of children. However, recent technological and clinical advances in genomic medicine have led to an increasing proportion being diagnosed with monogenic aetiologies of ALF. The conditions encountered include a diverse group of inherited metabolic disorders each with prognostic and treatment implications. Often these disorders are clinically indistinguishable and may even mimic disorders of immune regulation or red cell disorders. Rapid genomic sequencing for children with ALF is, therefore, a key component in the diagnostic work up today. This review focuses on the monogenic aetiologies of ALF.

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“…Despite the significant number of descriptions of intrauterine-or perinatal-onset of FHL, it is not possible to estimate the frequency of these cases (15). Fetal-onset FHL is considered the most severe form of the disease and carries a high mortality, close to 95% (48,49).…”

Section: Familial Hemophagocytic Lymphohistiocytosismentioning

confidence: 99%

Inborn Errors of Immunity With Fetal or Perinatal Clinical Manifestations

et al. 2022

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In this article we revised the literature on Inborn Errors of Immunity (IEI) keeping our focus on those diseases presenting with intrauterine or perinatal clinical manifestations. We opted to describe our findings according to the IEI categories established by the International Union of Immunological Societies, predominantly addressing the immunological features of each condition or group of diseases. The main finding is that such precocious manifestations are largely concentrated in the group of primary immune regulatory disorders (PIRDs) and not in the group of classical immunodeficiencies. The IEI categories with higher number of immunological manifestations in utero or in perinatal period are: (i) diseases of immune dysregulation (HLH, IPEX and other Tregopathies, autosomal recessive ALPS with complete lack of FAS protein expression) and (ii) autoinflammatory diseases (NOMID/CINCA, DIRA and some interferonopathies, such as Aicardi-Goutières syndrome, AGS, and USP18 deficiency). Regarding the other IEI categories, some patients with Omenn syndrome (an atypical form of SCID), and a few X-linked CGD patients present with clinical manifestations at birth associated to immune dysregulation. The most frequent clinical features were hydrops fetalis, intrauterine growth retardation leading to fetal loss, stillbirths, and prematurity, as in HLH and IPEX. Additionally, pseudo-TORCH syndrome was observed in AGS and in USP18 deficiency. The main goal of our review was to contribute to increasing the medical awareness of IEI with intrauterine and perinatal onset, which has obvious implications for diagnosis, treatment, and genetic counseling.

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Exome sequencing detected an extremely rare case of foetal onset familial haemophagocytic lymphohistiocytosis type 5 presenting with hydrops foetalis

Cited by 3 publications

References 15 publications

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

Genetic aetiologies of acute liver failure

Inborn Errors of Immunity With Fetal or Perinatal Clinical Manifestations

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