Pediatric diabetes mellitus hospitalizations and COVID-19 pandemic response measures.

AIMS: In the United States, evidence suggests that during the COVID-19 pandemic, admissions of patients with diabetes mellitus (DM) have increased. This study assessed hospital admission rates for pediatric type 1 (T1DM) and type 2 (T2DM) diabetes mellitus during 2019-2021, and the potential influence of the timing of various pandemic response measures. METHODS: Retrospective chart reviews were conducted of 854 T1DM and 135 T2DM hospital admissions between January 2019 and December 2021 in patients < 20 years old to collect demographic data, admission type, body mass index (BMI), and area deprivation index (ADI, a measure of socioeconomic vulnerability). Patients were divided into three cohorts based on their admission year: 2019 (Pre-pandemic), 2020 (Pandemic, Pre-vaccine), and 2021 (Pandemic, Post-vaccine). Admissions were categorized within each cohort by diagnosis (T1DM or T2DM) and clinical presentation (new onset, diabetic ketoacidosis: DKA). Cohorts were compared using an independent samples t-test for continuous variables or a chi-square test for categorical variables. RESULTS: The incidence of T2DM hospitalizations tripled during the pandemic, increasing from 18 in 2019 (Pre-pandemic), to 55 in 2020 (Pandemic, Pre-vaccine), and 62 in 2021 (Pandemic, Post-vaccine). The rate of patients presenting with DKA was 15.4 % (95 % CI: 4 %-26.9 %) higher in 2020 (Pandemic, Pre-vaccine) among patients with new-onset T1DM (72/139 vs. 52/143), and 22.5 % (95 % CI: 9.6 %-35.4 %) higher in 2020 (Pandemic, Pre-vaccine) among T2DM patients (9/40 vs. 0/14). This increased rate of new onset T2DM significantly correlated with younger age (P = 0.046) and higher ADI score (P = 0.017), but not with BMI. CONCLUSION: The incidence of T1DM hospitalizations did not increase during the pandemic; however, they tripled for T2DM patients. All new onset DM pediatric patients during the pandemic were more likely to present in DKA. Patients admitted with new onset T2DM were socioeconomically more vulnerable. For T1DM, the peak of local pediatric diabetes admissions in 2020 occurred slightly later coinciding with the reopening of primary care physicians (PCP) offices and schools.

Clinical and molecular phenotyping of a child with Hermansky-Pudlak syndrome-7, an uncommon genetic type of HPS.

PURPOSE: Hermansky-Pudlak syndrome (HPS) is a rare inherited disorder with ten reported genetic types; each type has defects in subunits of either Adaptor Protein-3 complex or Biogenesis of Lysosome-related Organelles Complex (BLOC)-1, -2, or -3. Very few patients with BLOC-1 deficiency (HPS-7, -8, and -9 types) have been diagnosed. We report results of comprehensive clinical testing and molecular analyses of primary fibroblasts from a new case of HPS-7. RESULTS: A 6-year old Paraguayan male presented with hypopigmentation, ocular albinism, nystagmus, reduced visual acuity, and easy bruising. He also experienced delayed motor and language development as a very young child; head and chest trauma resulted in intracranial hemorrhage with subsequent right hemiparesis and lung scarring. There was no clinical evidence of immunodeficiency or colitis. Whole mount transmission electron microscopy revealed absent platelet delta granules; platelet aggregation testing was abnormal. Exome sequencing revealed a homozygous nonsense mutation in the Dystrobrevin binding protein 1 (DTNBP1) gene [NM_032122.4: c.307C>T; p.Gln103*], previously reported in a Portuguese adult. The gene encodes the dysbindin subunit of BLOC-1. Dysbindin protein expression was negligible in our patient's dermal fibroblasts, while his DTNBP1 mRNA level was similar to that of a normal control. CONCLUSIONS: Comprehensive clinical evaluation of the first pediatric case reported with HPS-7 reveals oculocutaneous albinism and platelet storage pool deficiency; his phenotype is consistent with findings in other patients with BLOC-1 disorders. This patient's markedly reduced Dysbindin protein expression in HPS-7 resulted from a mechanism other than nonsense mediated decay.

Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects.

BACKGROUND: Laminins are heterotrimeric complexes, consisting of α, ß and γ subunits that form a major component of basement membranes and extracellular matrix. Laminin complexes have different, but often overlapping, distributions and functions. METHODS: Under our clinical protocol, NCT00068224, we have performed extensive clinical and neuropsychiatric phenotyping, neuroimaging and molecular analysis in patients with laminin α1 (LAMA1)-associated lamininopathy. We investigated the consequence of mutations in LAMA1 using patient-derived fibroblasts and neuronal cells derived from neuronal stem cells. RESULTS: In this paper we describe individuals with biallelic mutations in LAMA1, all of whom had the cerebellar dysplasia, myopia and retinal dystrophy, in addition to obsessive compulsive traits, tics and anxiety. Patient-derived fibroblasts have impaired adhesion, reduced migration, abnormal morphology and increased apoptosis due to impaired activation of Cdc42, a member of the Rho family of GTPases that is involved in cytoskeletal dynamics. LAMA1 knockdown in human neuronal cells also showed abnormal morphology and filopodia formation, supporting the importance of LAMA1 in neuronal migration, and marking these cells potentially useful tools for disease modelling and therapeutic target discovery. CONCLUSION: This paper broadens the phenotypes associated with LAMA1 mutations. We demonstrate that LAMA1 deficiency can lead to alteration in cytoskeletal dynamics, which may invariably lead to alteration in dendrite growth and axonal formation. Estimation of disease prevalence based on population studies in LAMA1 reveals a prevalence of 1-20 in 1 000 000. TRIAL REGISTRATION NUMBER: NCT00068224.

A clinical report of Chediak-Higashi syndrome in infancy with a novel genotype from the Indian subcontinent.

Chediak-Higashi syndrome (CHS; OMIM no. 214500) is an inherited multisystem disorder presenting with hypopigmentation and a propensity to infections due to immunological dysfunction. CHS generally presents in infancy with a fatal outcome, but less severe cases can present in adulthood. Treatment with bone marrow transplantation can be life-saving, so establishing a correct diagnosis is critical. The presence of large granules on examination of peripheral blood smears is suggestive of the diagnosis of CHS in most centers. However, sequencing of the lysosomal trafficking, LYST, gene confirms the diagnosis and can provide a prognosis regarding disease severity. In the case presented here, we performed molecular testing to identify the causative mutation and tabulated published mutation data from 2009 to 2014. We found a novel frameshift mutation in our case and concluded that frameshift and nonsense are the most common types of mutation in CHS, but this may be biased due to underdiagnosis of the milder and atypical forms of the disease.