Fatal Neonatal DOLK-CDG as a Rare Form of Syndromic Ichthyosis

Neonatal collodion baby or ichthyosis can pose a diagnostic challenge, and in many cases, only additional organ involvement or the course of the disease will help differentiate between non-syndromic and syndromic forms. Skin abnormalities are described in about 20% of the congenital disorders of glycosylation (CDG). Among those, some rare CDG forms constitute a special group among the syndromic ichthyoses and can initially misdirect the diagnosis towards non-syndromic genodermatosis. DOLK-CDG is such a rare subtype, resulting from a defect in dolichol kinase, in which the congenital skin phenotype (often ichthyosis) is later associated with variable extracutaneous features such as dilatative cardiomyopathy, epilepsy, microcephaly, visual impairment, and hypoglycemia and may lead to a fatal course. We report two neonatal cases of lethal ichthyosis from the same family, with distal digital constrictions and a progressive course leading to multi-organ failure and death. Postmortem trio whole-exome sequencing revealed the compound heterozygous variants NM_014908.3: c.1342G>A, p.(Gly448Arg) and NM_014908.3: c.1558A>G, p.(Thr520Ala) in the DOLK gene in the first affected child, which were confirmed in the affected sibling. Reduced staining with anti-α-Dystroglycan antibody was observed in frozen heart tissue of the second child as an expression of reduced O-mannosylation due to the dolichol kinase deficiency. In addition to the detailed dermatopathological changes, both cases presented hepatic and extrahepatic hemosiderosis on histological examination. Our patients represent an early and fatal form of DOLK-CDG with a striking presentation at birth resembling severe collodion baby. Both cases emphasize the phenotypic variability of glycosylation disorders and the importance to broaden the differential diagnosis of ichthyosis and to actively search for organ involvement in neonates with ichthyosis.

A RARE CASE OF HARLEQUIN ICHTHYOSIS SUCCESSFULLY TREATED WITH ACITRETIN: A CASE REPORT AND LITERATURE REVIEW

Harlequin Ichthyosis is the most serious congenital keratinization disorder. When the children are born, they are enveloped in thick horn armor. They are thick yellow horn plates that tear deeply when they dry out. In the most severe form, the children often die in the first few weeks of life. But there are also many milder courses, whereby there are obviously flowing transitions from collodion baby to harlequin ichthyosis. The skin condition later corresponds to that of a child with severe congenital ichthyosis (ARCI). Similar to the collodion baby, cases of harlequin ichthyosis should initially be cared for in the intensive care unit for newborns and require interdisciplinary therapy. Harlequin ichthyosis is caused by very special mutations in the ABCA12 gene. These mutations also have an impact on survival. If homozygous mutations are present, the prospects are worse than if the parents have heterozygous mutations. Homozygous mutations are often present when the parents are consanguineous.

Do Not Miss the (Genetic) Diagnosis of Gaucher Syndrome: A Narrative Review on Diagnostic Clues and Management in Severe Prenatal and Perinatal-Lethal Sporadic Cases

With a growing number of proved therapies and clinical trials for many lysosomal storage disorders (LSDs), a lot of hope for many patients and families exists. However, there are sometimes cases with poor prognosis, fatal outcomes when our efforts must be directed towards a prompt and correct genetic diagnosis, which offers the only possibility of providing the family with appropriate prevention and treatment. To address this issue, in this article, we present the clinical and genetic hallmarks of the lethal form of Gaucher disease (PLGD) and discuss the potential management. We hope that this will draw attention to its specific manifestations (such as collodion-baby phenotype, ichthyosis, arthrogryposis), which differ from best-known GD complications and ensure appropriate diagnostic assessment to provide families at risk with reliable counselling and treatment to avoid the medical complication of GD.

Report of a Novel ALOX12B Mutation in Self-Improving Collodion Ichthyosis with an Overview of the Genetic Background of the Collodion Baby Phenotype

Collodion baby is a congenital, transient phenotype encountered in approximately 70–90% of autosomal recessive congenital ichthyosis and is an important entity of neonatal erythroderma. The clinical outcome after this severe condition is variable. Genetic mutations of components of the epidermal lipoxygenase pathway have been implicated in the majority of self-improving collodion ichthyosis (SICI). In SICI, the shedding of the collodion membrane reveals clear skin or only mild residual manifestation of ichthyosis. Here we report the case of a girl born with a severe form of collodion baby phenotype, whose skin almost completely cleared within the first month of life. At the age of 3 years, only mild symptoms of a keratinization disorder remained. However, the severity of erythema and scaling showed mild fluctuations over time. To objectively evaluate the skin changes of the patient, we assessed the ichthyosis severity index. Upon sequencing of the ALOX12B gene, we identified a previously unreported heterozygous nonsense mutation, c.1607G>A (p.Trp536Ter) with the recurrent, heterozygous mutation c.1562A>G (p.Tyr521Cys). Thereby, our findings expand the genotypic spectrum of SICI. In addition, we summarize the spectrum of further genetic diseases that can present at birth as collodion baby, in particular the SICI.

Collodion Baby in a Sudanese patient

The aim of my clinical image is to recall this rare dermatological condition and to highlight instructions to follow in treatment and proper management of the complications that can arise.

Ichthyosis: case report in a Colombian man with genetic alterations in ABCA12 and HRNR genes

Background Ichthyosis is a heterogeneous group of diseases caused by genetic disorders related to skin formation. They are characterized by generalized dry skin, scaling, hyperkeratosis and frequently associated with erythroderma. Among its different types, harlequin ichthyosis (HI) stands out due to its severity. HI is caused by mutations in the ABCA12 gene, which encodes essential proteins in epidermal lipid transport, and it helps maintain the homeostasis of the stratum corneum of the epidermis. However, due to the wide spectrum of genetic alterations that can cause ichthyosis, holistic medical care, and genetic studies are required to improve the diagnosis and outcomes of these diseases. Case presentation Here, we presented the case of a 19 years old male patient who was a premature infant and exhibited clinical features consistent with HI, including bright yellow hyperkeratotic plates with erythematous fissures that covered his entire body like a collodion baby. Currently, he exhibited erythroderma, photosensitivity, ectropion, auricular pavilion alterations, and musculoskeletal disorders, such as equinovarus feet, fingers, hands, and hypoplastic feet with contractures in flexion and marked difficulty in fine motor skills. In addition, he presented dyschromatopsia, Achilles reflex hyporeflexia, slight speech, dental alteration and deficient cognitive performance. After the genetic sequencing, variants were found in ABCA12 and HRNR which are related to several skin diseases, including ichthyosis. Conclusions Although in clinical practice, ichthyosis is a common entity, a severe type of ichthyosis is presented, highlighting the importance of appropriate genetic diagnosis, given the broad spectrum of genetic alterations with similar phenotypic and clinical characteristics. These pathologies must be known to guarantee initial support measures to prevent complications and offer multidisciplinary management to those patients.