NovelPGM3compound heterozygous variants with IgE‐related dermatitis, lymphopenia, without syndromic features

Abstract

Background: Phosphoglucomutase-3 (PGM3) deficiency is a congenital disorder of glycosylation (CDG) with hyperimmunoglobulin IgE, atopy, and a variable immunological phenotype; most reported patients display dysmorphic features. The aim of the study was to characterize the genotype and phenotype of individuals with newly identified compound heterozygous variants in the phosphate-binding domain of PGM3 in order to better understand phenotypic differences between these patients and published cases. Methods: We analyzed PGM3 protein expression, PGM3 enzymatic activity, the presence of other gene variants within the N-glycosylation pathway, and the clinical and immunological manifestations of two affected siblings. Results: Patients belonged to a non-consanguineous family, presenting with atopic dermatitis, elevated levels of IgE, and CD4 + lymphopenia (a more severe phenotype was observed in Patient 2), but lacked dysmorphic features or neurocognitive | 567 GARCÍA-GARCÍA et Al.

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

“…Hypomorphic phosphoglucomutase 3 ( PGM3) mutations with autosomal recessive transmission cause abnormal protein glycosylation and differences in the cellular metabolism. The clinical presentation is characterized by high serum IgE, atopy, neurological impairment, immunodeficiency and autoimmunity ( 95 ). In fact, it was demonstrated that altered glycosylation due to PGM deficiency may also affect a subset of lymphocytes ( 96 , 97 ).…”

When to Worry It’s More than Atopic Dermatitis

“…Manifestations include elevated IgE, myoclonus, neurocognitive impairment, recurrent viral and pulmonary infections and an eczematous rash. 29 The cutaneous involvement may manifest similarly to those with atopy, including development of allergies and asthma. 30,31 IMMUNE DYSREGULATION POLYENDOCRINOPATHY ENTEROPATHY X-LINKED (IPEX)…”

“Inborn errors of immunity: An expanding horizon through a multitude of biological pathways”

“…The validity of the disease categories derived from this exercise relies heavily on the continuous confirmation and updating of such phenotypic features. In this context, the virtual issue on “Inborn Errors of Immunity” aims at providing the readers of PAI a collection of topical reviews on some of the major immunological pathways that can be affected by pathological genetic variants causing IEIs and a selection of original articles highlighting clinical observations from cohort studies of well‐known conditions, as well as original discoveries that extend the genetic and clinical features of less commonly observed IEIs 1–17 …”

“…In this context, the virtual issue on "Inborn Errors of Immunity" aims at providing the readers of PAI a collection of topical reviews on some of the major immunological pathways that can be affected by pathological genetic variants causing IEIs and a selection of original articles highlighting clinical observations from cohort studies of well-known conditions, as well as original discoveries that extend the genetic and clinical features of less commonly observed IEIs. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] In their review of IEIs caused by defects in the DNA damage response pathways, Fournier and Colleagues 3 Additional reviews of the areas of IEIs characterized by defects of actin cytoskeletal dynamics, the JAK-STAT pathways, and type I interferon disorders have been commissioned and will be available in the near future. These works will complement the current collection and provide the readers of PAI with additional timely updates and perspectives on the scientific and clinical aspects of some of the major disease subgroups in the field of IEIs.…”