Case Report: Severe vitamin D deficiency in a girl with inflammatory myopathy and myonecrosis.

Inflammatory myopathies are a rare group of disorders that can cause significant disruption in the ability of an individual to adequately perform activities of daily living. In this case report, we present a case of a girl presenting with a substantial compromise of her ambulation with a muscle biopsy consistent with myonecrosis. She was subsequently diagnosed with an inflammatory myopathy and started on glucocorticoid and methotrexate therapy with minimal symptomatic improvement. Further in her clinical course, hypocalcemia and an undetectable 25-hydroxyvitamin D level were detected. Prompt institution of calcium and vitamin D supplementation significantly improved her myopathic condition. While there is evidence in the literature linking vitamin D deficiency with myopathy, there is a lack of data on the association between hypocalcemia and vitamin D deficiency with myonecrosis, which could represent comorbid states in myonecrosis. Therefore, vitamin D status should be established in all patients with myonecrosis, as vitamin D deficiency is easy to diagnose and treat, as exemplified in our patient's case, which shows that such treatment could lead to significant clinical improvement.

Genetic testing for maturity-onset diabetes of the young resulting in an upgraded genetic classification of an HNF1A gene variant: a case report.

The frequent misdiagnosis of MODY (Maturity-Onset Diabetes of the Young) subtypes makes it necessary to clarify the clinical spectrum of the disease phenotypes in suspected subjects so that accurate diagnosis and management plans can be introduced as early as possible in the course of the disease. We report the case of a MODY subtype that was initially characterized as variant of uncertain significance (VUS) but was later changed to a likely pathogenic variant following our report of two cases where the full expression of the clinical phenotype was described. HNF1A-MODY (Maturity Onset Diabetes of the Young type 3) is one of the most common subtypes of MODY. Due to its variable clinical presentation, and the concerns with being misdiagnosed as either type 1 or type 2 diabetes, DNA sequencing is needed to confirm the diagnosis. This case report illustrates the clinical scenario leading to the identification of the gene variant c.416T>C(p. Leu139Pro) in the HNF1A gene, initially reported as a VUS and later upgraded to a likely pathogenic variant. Though the mutation was described in two Czech family members in 2020, the clinical course and phenotype was not characterized. Therefore, there was the need to fully describe the spectrum of the disease arising from the mutation. The case report fully describes the clinical spectrum of this mutation and provides much needed clinical management approaches to the wider scientific community.

Novel duplication of the cell adhesion molecule L1-like gene in an individual with cognitive impairment, tall stature, and obesity: A case report.

The gene that codes for the close homolog of L1 (CHL1 gene) is located in the 3p26.3 cytogenetic band in the distal portion of the 3p chromosome. This gene is highly expressed in the central nervous system and plays an important role in brain formation and plasticity. Complete or partial CHL 1 gene-deficient mice have demonstrated neurocognitive deficits. In humans, mutations of the CHL 1 gene are infrequent with most mutations described in the literature as deletions. This case report describes an individual with a duplication in the CHL 1 and a presentation consistent with a syndromic form of neurocognitive impairment. To the best of our knowledge, this mutation has not been previously described in the literature.

Ossifications in Albright Hereditary Osteodystrophy: Role of Genotype, Inheritance, Sex, Age, Hormonal Status, and BMI.

Context: Albright hereditary osteodystrophy (AHO) is caused by heterozygous inactivating mutations in GNAS. Depending on the parental origin of the mutated allele, patients develop either pseudohypoparathyroidism type 1A (PHP1A), with multihormone resistance and severe obesity, or pseudopseudohypoparathyroidism (PPHP), without hormonal abnormalities or marked obesity. Subcutaneous ossifications (SCOs) are a source of substantial morbidity in both PHP1A and PPHP. Objective: This study investigated the previously undetermined prevalence of SCO formation in PHP1A vs PPHP as well as possible correlations with genotype, sex, age, hormonal resistance, and body mass index (BMI). Design: This study evaluated patients with AHO for SCOs by physical examination performed by one consistent physician over 16 years. Setting: Albright Clinic, Kennedy Krieger Institute; Institute for Clinical and Translational Research, Johns Hopkins Hospital; Albright Center, Connecticut Children's Medical Center. Patients: We evaluated 67 patients with AHO (49 with PHP1A, 18 with PPHP) with documented mutations in GNAS. Main Outcome Measures: Relationships of SCOs to genotype, sex, age, hormonal resistance, and BMI. Results: Forty-seven of 67 participants (70.1%) had SCOs. Patients with PHP1A and PPHP had similar prevalences and degrees of ossification formation. Patients with frameshift and nonsense mutations had much more extensive SCOs than those with missense mutations. Males were affected more than females. There was no correlation with hormonal status or BMI. Conclusions: There is a similar prevalence of SCOs in PHP1A and PPHP, and the extent of SCO formation correlates with the severity of the mutation. Males are affected more extensively than females, and the SCOs tend to worsen with age.