Aminoacyl-tRNA synthetases play a pivotal role in catalyzing the precise coupling of amino acids with their corresponding tRNAs. Among them, Tyrosyl tRNA synthetase, encoded by the YARS1 gene, facilitates the aminoacylation of tyrosine to its designated tRNA. Heterozygous variants in the YARS1 gene have been linked to autosomal dominant Charcot-Marie-Tooth type C, while recent findings have unveiled biallelic YARS1 variants leading to an autosomal recessive multisystemic disorder in several cases. In this report, we present a novel case characterized by dysmorphic facies, and multisystemic symptoms, prominently encompassing neurological issues and a microarray conducted shortly after birth revealed 47, XXY. Utilizing whole exome sequencing, we uncovered a paternally inherited likely pathogenic variant (c.1099C > T, p.Arg367Trp), previously reported, coinciding with the father\'s history of hearing loss and neurological symptoms. Additionally, a maternally inherited variant of uncertain significance (c.782T > G, p.Leu261Arg), previously unreported, was identified within the YARS1 gene. The observed phenotypes and the presence of compound heterozygous results align with the diagnosis of an autosomal recessive disorder associated with YARS1. Through our cases, the boundaries of this emerging clinical entity are broadened. This instance underscores the significance of comprehensive genetic testing in patients exhibiting intricate phenotypes.

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Hypophosphatasia is a rare inherited disease defined by teeth and bone mineralization impairment leading to depletion of tissue non-specific alkaline phosphatase. We define a young woman diagnosed with hypophosphatasia (after several times alkaline phosphatase levels were low) was discovered following femoral fracture. A 30-year-old woman who presented for a history of early permanent teeth loss during the last 5 years and HPP-like symptoms in family history and bone radiograph verified bowing, deficient mineralization, and symmetrical subtrochanteric stress fractures of femurs was referred to our clinic for further management. Blood test findings defined raised phosphorus levels on two occasions at 6.2 and 5.7 mg/dl and insufficient 25-hydroxy vitamin D level. HPP early diagnosis and adequate treatment, depending on the clinical symptoms along with laboratory tests, could be effective in decreasing the suffering of the disease and side effects.

Malignant otitis externa (MOE) is an uncommon, potentially life-threatening, invasive infection of the external auditory canal and lateral skull base. It is mainly seen in older adults with diabetes or immunocompromised patients and rarely seen in children. Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis disorder. It is a multisystem disease with a poorly understood etiology. It commonly affects the skeletal system, central nervous system (CNS), cardiovascular system, lungs, retroperitoneum, kidneys, and skin. CNS involvement confers poor prognosis and reduced response to treatment. Cardiovascular involvement is another indicator of poor prognosis. This report describes the case of a 20-year-old male with ECD who had bilateral malignant otitis externa/skull base osteomyelitis and hearing loss. The patient was not responding well to treatment. He was on intravenous antibiotics, underwent left mastoidectomy, received targeted immunotherapy, and had four rounds of chemotherapy. The patient died after six months from the diagnosis and targeted treatment, which indicates the aggressiveness of the disease. MOE should be suspected in any patient presenting with intractable otalgia with otorrhea that is not responsive to local treatment for uncomplicated otitis externa or otalgia with temporomandibular joint (TMJ) pain aggravated by chewing. This is the first report of malignant otitis externa in a young patient with ECD to the best of the author\'s knowledge. This case emphasizes the importance of suspecting MOE in young patients, especially if the risk factors of the disease are present because early diagnosis can prevent or minimize life-threatening complications.

Langerhans cell histiocytosis (LCH) is due to aberrant monoclonal proliferation and accumulation of dendritic cells, ranging from a self-limiting local condition to a rapidly progressive multisystem disease with poor prognosis. Pathogenic cells originate from a myeloid-derived precursor characterized by an activation of the MAPK/ERK signaling pathway in about 70% of cases. In particular, BRAF V600E mutation is usually associated with a more severe clinical course and poor response to chemotherapy. We report on a newborn with multisystem LCH in life-threatening medical conditions. At diagnosis, the patient was successfully treated with the early association of BRAF inhibitor Vemurafenib to standard chemotherapy representing a new approach in first-line treatment. A rapid clinical improvement with a prompt fever regression from day 2 and complete resolution of skin lesions by week 2 were observed; laboratory data normalized as well. Vemurafenib was discontinued after 12 months of treatment. No signs of relapse occurred after 12 months of discontinuation. This case indicates that early combination of target therapy with standard treatment may induce rapid response and prolonged disease remission without significant toxicities in infants. This approach represents a valid and safe option as first-line treatment in multisystem disease, especially in high-risk patients.

Langerhans cell histiocytosis (LCH) is a disorder characterized by accumulation of Langerhans-like cells in one or various organs. A correct staging work-up is essential since there are multiorgan presentations with a poor prognosis. We report three patients with LCH skin lesions mimicking molluscum contagiosum in association with both high and low risk organ involvement. This peculiar cutaneous presentation can be a clue for the diagnosis of LCH, a disease with potentially severe systemic involvement.

UNASSIGNED: The clinical presentation of Langerhans cell histiocytosis (LCH) is heterogeneous ranging from single-organ involvement to systemic disease causing substantial morbidity and mortality. We describe an unusual course of severe multisystem LCH with spontaneous remission.
UNASSIGNED: We report on a 45-year-old Caucasian woman with cervical cancer, FIGO stage IVB. Five months after the end of combined radiochemotherapy and brachytherapy, the patient was readmitted because of severe dysuria. Sterile leukocyturia was seen, and cystoscopy revealed only 3 unspecific small mucosal lesions compatible with postradiation cystitis. Incidentally, a computed tomography (CT) scan of the body showed diffuse micronodular and cystic lesions in lungs and hypodense lesions in the liver. Biopsies revealed infiltrations of CD1a and Langerin (CD207)-positive histiocytes in the lung, liver, and bladder. Additionally, positron emission tomography-CT (PET-CT) was compatible with bone involvement. Retrospective analysis revealed that the increase in alkaline phosphatase might have been a surrogate of bone marrow infiltration with osseous activity. Repeated pneumothoraces occurred, and only one course of vinblastine-prednisolone could be applied. Despite ongoing tobacco consumption and without further therapy, PET-CT showed considerable remission 2 months later. However, despite stable remission, documented by serial PET and conventional CT scans, persistent infiltration of the bladder by Langerhans histiocytes could still be demonstrated 17 months later. Unfortunately, cervical cancer recurred and progressed.
UNASSIGNED: Multisystem LCH may rapidly occur, may be oligosymptomatic and, even in high-risk cases, remission without specific therapy might occur. Whether alkaline phosphatase might be a surrogate to monitor osseous disease activity has to be further explored.