JAK Inhibition in a Patient with X-Linked Reticulate Pigmentary Disorder
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LETTER TO EDITOR
JAK Inhibition in a Patient with X-Linked Reticulate Pigmentary Disorder Corinne Légeret 1 & Benedikt J. Meyer 2 & Annette Rovina 2 & Nikolaus Deigendesch 3 & Christoph T. Berger 4 & Thomas Daikeler 5 & Ingmar Heijnen 6 & Ezra Burstein 7 & Henrik Köhler 1 & Mike Recher 2 Received: 4 June 2020 / Accepted: 14 September 2020 # The Author(s) 2020
To the editor, X-linked reticulate pigmentary disorder (XLPDR) is a very rare inherited disease with prominent skin hyperpigmentation and multiorgan involvement dominated by autoinflammatory manifestations in the eyes, the urinary tract, and recurrent infections, particularly in the respiratory tract. In 2016, the causative genetic mutation for XLPDR was located to the POLA1 gene, which encodes the catalytic subunit of DNA polymerase A1 [1]. An intronic POLA1 mutation (c.1375354A>G), causing altered POLA1 gene splicing, leads to reduced transcript and protein levels. It has been demonstrated that POLA1 deficiency is directly linked to the activation of type I interferons (IFNs) and upregulation of interferonstimulated genes (ISG), classifying XLPDR as an interferonopathy [1]. In affected males, the disease typically manifests in the first months of life with failure to thrive, recurrent pneumonias, persistent diarrhea in infancy, and pathognomonic diffuse hyperpigmentation and characteristic facies [2]. The patient described here was born in 2008 into a Caucasian, non-consanguineous family via spontaneous vaginal delivery at term. The index patient has two older, healthy
brothers and healthy parents. His mother lacked pigmentary changes along Blaschko’s lines. At the age of four weeks, he was admitted to the hospital due to low weight for age (Fig. S1). During the admission, he developed mild bloody diarrhea. All laboratory tests performed at that time (blood count, electrolytes, liver parameters, clotting time, thyroid function, viral serologies, screening for inborn metabolic disorders, stool screenings for malabsorption, and infections) were within reference ranges. The hypothesis of a cow’s milk protein allergy was made, the formula was swapped to an amino acid based one, the symptoms resolved, and the patient started to gain weight. Since the age of six months, his weight follows percentiles 3–15 (Supplementary Fig. 1). On clinical examination during the hospitalization, a mild muscular hypotonia was noticed and further tests (MRI of the head, abdominal ultrasound, EEG, and referral to the ophthalmologist) were arranged—all with normal results. Neuropediatric follow-up was arranged due to the mild muscular hypotonia but was stopped at the age of 2 years because a normal development was objectified. Over the next years, the patient suffered from recurrent otitis media, sinusitis, and several pneumonias. Despite the performance of an adenoidectomy,
Corinne Légeret and Benedikt J. Meyer contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00867-7) contains supplementary
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