Ichthyosis prematurity syndrome in two Omani siblings, caused by homozygous c.1A &gt; G mutation in the <i>FATP4</i> gene

Mandhari, Hilal Al; Al-Musalhi, Buthaina; Mahroqi, Nouh Al; Hilmarsen, Hilde Tveitan; Braathen, Geir J.; Khnykin, Denis

doi:10.1111/ijd.15367

Cited by 6 publications

(3 citation statements)

References 18 publications

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“…IPS is a rare disease commonly seen in Sweden and Norway, and some cases are reported in other European countries, Africa, and Asia. On our review of case reports, eosinophilia was reported to be transient in four baby boys ( 70 – 73 ) and a baby girl ( 74 ) with IPS and FATP4 mutations. However, persistent eosinophilia was reported in two female patients with IPS at the age of 14 ( 75 ) and 27 ( 76 ).…”

Section: Discussionmentioning

confidence: 93%

Myeloid-specific fatty acid transport protein 4 deficiency induces a sex-dimorphic susceptibility for nonalcoholic steatohepatitis in mice fed a high-fat, high-cholesterol diet

Göcebe

Jansakun

Zhang

et al. 2023

American Journal of Physiology-Gastrointestinal and Liver Physi

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Newborns with FATP4 mutations exhibit ichthyosis prematurity syndrome (IPS), and adult patients show skin hyperkeratosis, allergies, and eosinophilia. We have previously shown that the polarization of macrophages is altered by FATP4 deficiency, however, the role of myeloid FATP4 in the pathogenesis of non-alcoholic steatohepatitis (NASH) is not known. We herein phenotyped myeloid-specific Fatp4-deficient (Fatp4M-/-) mice under chow and high-fat/high-cholesterol (HFHC) diet. Bone-marrow-derived macrophages (BMDMs) from Fatp4M-/- mice showed significant reduction in cellular sphingolipids in males and females, and additionally cellular phospholipids in females. BMDMs and Kupffer cells from Fatp4M-/- mice exhibited increased LPS-dependent activation of pro-inflammatory cytokines and transcription factors PPARγ, CEBPα, and p-FoxO1. Correspondingly, these mutants under chow diet displayed thrombocytopenia, splenomegaly, and elevated liver enzymes. After HFHC feeding, Fatp4M-/- mice showed increased MCP-1 expression in liver and subcutaneous fat. Plasma MCP-1, IL4, and IL13 levels were elevated in male mutants, and those of IL5 and IL6 were additionally elevated in female mutants. After HFHC feeding, male mutants showed an increase in hepatic steatosis and inflammation, while female mutants showed a greater severity in hepatic fibrosis associated with immune cell infiltration. Thus, myeloid-FATP4 deficiency led to steatotic and inflammatory NASH in males and females, respectively. Our work offers some implications for patients with FATP4 mutations, and also highlights considerations in the design of sex-targeted therapies for NASH treatment.

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Section: Discussionmentioning

confidence: 93%

Myeloid-specific fatty acid transport protein 4 deficiency induces a sex-dimorphic susceptibility for nonalcoholic steatohepatitis in mice fed a high-fat, high-cholesterol diet

Göcebe

Jansakun

Zhang

et al. 2023

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Mandhari et al 8 discussed two cases of IPS in Omani siblings, born at 35 and 33 weeks, both with mild respiratory symptoms that resolved with 2 days of non-invasive ventilation. They postulated that the severity of previously described respiratory distress may have been primarily related to the prematurity of reported cases as most reported cases were born at less than 34 weeks’ gestational age 10.…”

Section: Discussionmentioning

confidence: 99%

“…Prenatal ultrasound findings may raise suspicions of the disorder; however, these findings typically do not arise prior to 28 weeks. Originally described in Scandinavian countries, affected probands have now been identified throughout Europe,3–5 India,6 Japan,7 the Middle East and Africa 1 8. Due to its relatively indolent course during adulthood, it is likely that the prevalence of IPS is under-reported.…”

Section: Introductionmentioning

confidence: 99%

Experience of low-dose dexamethasone use in the respiratory management of ichthyosis prematurity syndrome

et al. 2021

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Ichthyosis prematurity syndrome (IPS) is a rare disorder of autosomal recessive inheritance. The cardinal features include prematurity, vernix like hyperkeratosis, eosinophilia and neonatal asphyxiation. This case report discusses the presentation and management of IPS. We aim to characterise the common features, the spectrum of disease within a single family and discuss a potential role for low-dose dexamethasone in the management of ventilator-dependent patients with IPS.

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Disorders of fatty acid homeostasis

Vaz,

Ferdinandusse,

Salomons

et al. 2024

J of Inher Metab Disea

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Humans derive fatty acids (FA) from exogenous dietary sources and/or endogenous synthesis from acetyl‐CoA, although some FA are solely derived from exogenous sources (“essential FA”). Once inside cells, FA may undergo a wide variety of different modifications, which include their activation to their corresponding CoA ester, the introduction of double bonds, the 2‐ and ω‐hydroxylation and chain elongation, thereby generating a cellular FA pool which can be used for the synthesis of more complex lipids. The biological properties of complex lipids are very much determined by their molecular composition in terms of the FA incorporated into these lipid species. This immediately explains the existence of a range of genetic diseases in man, often with severe clinical consequences caused by variants in one of the many genes coding for enzymes responsible for these FA modifications. It is the purpose of this review to describe the current state of knowledge about FA homeostasis and the genetic diseases involved. This includes the disorders of FA activation, desaturation, 2‐ and ω‐hydroxylation, and chain elongation, but also the disorders of FA breakdown, including disorders of peroxisomal and mitochondrial α‐ and β‐oxidation.

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Ichthyosis prematurity syndrome in two Omani siblings, caused by homozygous c.1A > G mutation in the FATP4 gene

Cited by 6 publications

References 18 publications

Myeloid-specific fatty acid transport protein 4 deficiency induces a sex-dimorphic susceptibility for nonalcoholic steatohepatitis in mice fed a high-fat, high-cholesterol diet

Myeloid-specific fatty acid transport protein 4 deficiency induces a sex-dimorphic susceptibility for nonalcoholic steatohepatitis in mice fed a high-fat, high-cholesterol diet

Experience of low-dose dexamethasone use in the respiratory management of ichthyosis prematurity syndrome

Disorders of fatty acid homeostasis

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