Ichthyosis lamellosa and congenital (with preserved transglutaminase activity) Q80.2

The family of autosomal recessive lamellar ichthyoses and congenital ichthyosiform erythroderma are rare, autosomal recessive inherited, usually severe (often collodion babies at birth) cornification anomalies that are etiopathogenetically caused by mutations in various genes (see classification below). About 60% of autosmal recessive congenital erythroderma affect this group. The ARCI group of ichthyoses refers to diseases that were previously referred to as ichthyosis congenita.

The family of autosomal recessive lamellarichthyoses (LI)/congenital ichthyosiform erythroderma (CIE) with preserved transglutaminase activity includes the following variations (the percentages given refer to the total group of autosomal recessive congenital ichthyoses - ACRI)

• LI/ CIE (ARCI 2) OMIM: 242100(ALOX12B) (7%)
• LI/ CIE (ARCI 3) OMIM: 242100(ALOXE3) (7%)
• LI/ CIE (ARCI 4A) OMIM: 60127(ABCA12)
• LI/ CIE (ARCI 5) OMIM: 604777(CYP4F22) (8%)
• LI/ CIE (ARCI 6) OMIM: 612281(NIPAL4) (16%)
• LI/ CIE (ARCI 8) OMIM: 613943(LIPN)
• LI/ CIE (ARCI9) OMIM: 615023(CERS3)
• LI/ CIE (ARCI 10) OMIM: 615024(PNPLA1)
• LI/ CIE (ARCI 11) OMIM: 6024(ST14)
• LI/ CIE (ARCI 12) OMIM: 617320(CASP14)

In the USA, the prevalence of ARCI is estimated at 1:200,000-300,000.

ARCI is associated with mutations in several genes, including ABCA12, ALOX12B, ALOXE3, CYP4F22, NIPAL4, TGM1, CERS3, PNPLA1, CASP14, SDR9C7 and SULT2B1 (Esperón-Moldes U et al. (2020). Most of these identified genes are involved in the synthesis of enzymes and transporters involved in the assembly, transport and/or composition of components of the stratum corneum (Kelly EJ et al. 2011).

A TGM1 gene mutation is the most common cause of ARCI and is closely associated with a collodion membrane at birth. Only 8% of ARCI cases are associated with a CYP4F22 mutation, making this mutant extremely rare.

ARCI can present at birth with a shiny, taut membrane consisting of a thickened stratum corneum called a collodion membrane (Traupe H et al. 2014). Although this is a common clinical manifestation of ARCI, patients with a CYP4F22 mutation usually present with erythroderma instead of a collodion membrane (Traupe H et al. 2014). When present, the collodion membrane dries out, ruptures and detaches over several weeks, revealing the underlying ARCI phenotype.

From birth

Already at birth picture of a very pronounced erythroderma, in the course of the first years of life eutliche regression; it remains in adolescence and adulthood a variably pronounced, but occasionally only discrete, generalized, fine gray-white scaling with pronounced palmo-Plantarkeratosen. All patients show heat intolerance due to reduced sweating. Particular attention should be paid to this in affected infants (collapse states possible).

Biochemical detection of transglutaminase deficiency in skin frozen sections. Detection of mutations in the various genes.

See below Ichthyoses.

The disorders are lifelong, but may show marked improvement in adulthood.

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