Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (MKD/HIDS) are disorders of cholesterol biosynthesis caused by variants in the MVK gene and characterized by increased urinary excretion of mevalonic acid. So far, 30 MVA patients have been reported, suffering from recurrent febrile crises and neurologic impairment. Here, we present an in‐depth analysis of the phenotypic spectrum of MVA and provide an in‐silico pathogenicity model analysis of MVK missense variants. The phenotypic spectrum of 11 MVA patients (age range 0‐51 years) registered in the Unified European Registry for Inherited Metabolic Disorders database was systematically analyzed using terms of the Human Phenotype Ontology. Biochemical, radiological as well as genetic characteristics were investigated. Six of eleven patients have reached adulthood and four have reached adolescence. One of the adolescent patients died at the age of 16 years and one patient died shortly after birth. Symptoms started within the first year of life, including episodic fever, developmental delay, ataxia, and ocular involvement. We also describe a case with absence of symptoms despite massive excretion of mevalonic acid. Pathogenic variants causing MVA cluster within highly conserved regions, which are involved in mevalonate and ATP binding. The phenotype of adult and adolescent MVA patients is more heterogeneous than previously assumed. Outcome varies from an asymptomatic course to early death. MVK variants cluster in functionally important and highly conserved protein domains and show high concordance regarding their expected pathogenicity.

No abstract

Background: Kawasaki disease (KD) is a systemic vasculitis which affects medium-sized arteries. Although diagnostic and classification criteria exist, differentiation from other diseases can be difficult.Case Presentation: We present a 3-year old patient with a diagnosis of complete KD with positivity for urine-PCR on leptospirosis. In our patient conjunctivitis, rash, fever, cervical lymphadenopathy, palmar swelling, exanthema were seen, indicating all criteria for complete KD. After 2 weeks periungual desquamation developed. Besides this patient two further cases were retrieved form the literature with similar clinical courses indicating leptospirosis associated KD.Conclusion: These cases indicate that leptospirosis may not only mimic but also be associated with KD shown by specific findings like desquamation of fingers, toes and oropharyngeal mucous membrane changes. To distinguish between KD, leptospirosis and leptospirosis associated KD a proper history taking including travel history and contact to animals is fundamental as well as thorough clinical and cardiac examinations in the course of the disease. While diagnostic procedures and observation might take time, treatment of acute KD should not be delayed.

ZUSAMMENFASSUNGEinleitung: Das Kawasaki-Syndrom (KS) ist eine systemische Vaskulitis, die mittelgroße Arterien betrifft. Obwohl Diagnose- und Klassifizierungskriterien existieren, kann die Abgrenzung von anderen Krankheiten schwierig sein.Falldarstellung: Bei einer 3-jährigen Patientin wurden neben Fieber folgende Symptome und Befunde festgestellt: Konjunktivitis, zervikale Lymphadenopathie, Palmarschwellung, gerötete und rissige Lippen sowie ein makulöses Exanthem. Diese Befunde sind mit einem kompletten KS vereinbar. Die Urin-PCR auf Leptospiren war positiv. Nach 2 Wochen entwickelte sich eine periunguale Schuppung.Diskussion: Dieser Fall zeigt, dass eine Leptospirose nicht nur ähnliche Symptome wie das KS aufweist, sondern auch mit dieser Erkrankung assoziiert sein kann. Dafür sprechen spezifische Befunde wie Schuppungen an Fingern, Zehen und Veränderungen der oropharyngealen Schleimhäute.

BackgroundFibrodysplasia ossificans progressiva (FOP) caused by mutations in the ACVR1 gene, which codes for activin receptor IA, a type I receptor of the bone morphogenetic protein (BMP) pathway. FOP is a very rare disease which usually begins in the first decade of life and characterized by congenital bilateral hallux valgus in combination with progressive heterotopic ossification in specific anatomical patterns preceded by inflammatory responses and soft tissue swelling.ObjectivesOur objective is to expand the differential diagnosis of recurrent swelling without trauma by presenting a case of Infant suffering from recurrent swellings and diagnosed to have FOP.MethodsWe used standard laboratory assessment and ultrasound to exclude other diseases. To confirm the diagnosis we used next generation sequencing to identify ACVR1 variants.ResultsA full-term male infant from non-consanguine parents delivered spontaneously after uncomplicated pregnancy. Initially bilateral hallux valgus, as well as limited motility in the metacarpophalangeal joint of D1 of the right hand was noted. At the age of 1.5 months, a severe swelling appeared on the left head without trauma. The further investigation showed no signs of retinal hemorrhage or intracranial injury. The swelling resolved spontaneously, but he readmitted to the hospital due to swellings of different localization in the head area. At the beginning a child abuse had been discussed with the family, although there was no concrete evidence.At the age of 7 months he presented to our center with renewed swelling in the area of the forehead. Due to the characteristic symptom constellation, a genetic analysis was performed on ACVR1, which confirmed a de novo mutation c.617G> A, p.R206H.We started a combined therapy with Montelukast 4 mg oral daily for specific inhibition of mast cell activation, Neridronat (Bisphosphonate) 2 mg/kg as i.v. every 3 months for the modification of secondary ossification. As well as Prednisolone for 3 days 20 mg/kg i.v. in the flare up.At the beginning there were a significant reduction in the frequency and severity of new swellings, however after 9 Months he had frequent flare up with limitation of head movement. At that point we decided to start an off-label therapy with Imatinib. He responded well to the current therapy and the medication is well tolerated.ConclusionFOP is a very rare and important differential diagnosis of child abuse. With the characteristic symptom of congenital bilateral hallux valgus and unclear swellings, the diagnosis can be genetically secured. An early specific treatment concept for the avoidance of trauma as well as drug-based anti-inflammatory therapy are crucial for the clinical course and subsequent impairment of the patient. New targeted treatment approaches offer a promising option for the long-term improvement of disease progression and associated quality of life like Imatinib, which is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia in adult and children. A recent article showed that...

No abstract