A Baby With Complete Androgen Insensitivity Syndrome and the Fortuitous Discovery of 45,X/46,XY Mosaicism.

Disorders of sex development (DSD) are caused by defects in the complex sexual differentiation cascade, resulting in discordance among an individual's genetic, gonadal, and genital sexes. It affects one in 4,500 live births. A wide spectrum of genital phenotypes can be found depending on the underlying pathogenic mechanism and the developmental stage that is affected. We herein report a newborn with female external genitalia but palpable gonads at labia majora with normal testicular function and structure, which is typical of complete androgen insensitivity syndrome (CAIS). The genetic study revealed 45,X/46,XY mosaicism and c.2081A>C missense androgen receptor gene mutation, indicating the likelihood of co-existing CAIS. This case demonstrated the importance of correlating genital phenotype and the underlying pathogenic mechanism, to provide appropriate management of DSD. Important considerations on managing the gonads about the risks of gonadal malignancies are also discussed.

Diabetic ketoacidosis in children with new-onset type 1 diabetes mellitus: demographics, risk factors and outcome: an 11 year review in Hong Kong.

OBJECTIVES: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes (T1D). The aim of this study is to analyze the incidence, clinical characteristics, management and outcome of children presenting with DKA in new-onset T1D from 2008 to 2018 in Hong Kong. METHODS: Data was extracted from the Hong Kong Childhood Diabetes Registry. All subjects less than 18 years with newly diagnosed T1D from 1 January 2008 to 31 December 2018 managed in the public hospitals were included. Information on demographics, laboratory parameters, DKA-related complications and management were analyzed. RESULTS: In the study period, there were 556 children with newly diagnosed T1D in our registry and 43.3% presented with DKA. The crude incidence rate of new-onset T1D with DKA was 1.79 per 100,000 persons/year (CI: 1.56-2.04). Subjects presenting with DKA were younger (9.5 ± 4.5 vs. 10.5 ± 4.4, p=0.01) and had shorter duration of symptoms (4.2 ± 5.9 days vs. 10.6 ± 17.1 days, p<0.01). Regarding management, up to 12.4% were given insulin boluses and 82.6% were started on insulin infusion 1 h after fluid resuscitation. The rate of cerebral edema was 0.8% and there was no mortality. CONCLUSIONS: Younger age and shorter duration of symptoms were associated with DKA in new-onset T1D. Despite availability of international guidelines, there was inconsistency in acute DKA management. These call for a need to raise public awareness on childhood diabetes as well as standardization of practice in management of pediatric DKA in Hong Kong.

Identification and Mapping of a 2,009-bp DNA Deletion in SERPING1 of a Hereditary Angioedema Patient.

We report a heterozygous, 2,009 base pairs (bps) genomic DNA deletion within the SERPING1 gene that has not previously been reported in a case of type I hereditary angioedema (HAE). The patient is a 28-year-old Han Chinese female living in Hong Kong who has suffered from recurrent angioedema since adolescence, with increasing attack frequency as she entered adulthood; in the past, episodes occurred annually, but now occur every two to three months. The affected areas are not itchy and include common sites such as the left and right forearms, but without throat involvement. The patient also experiences epigastric pain. The patient's mother suffers from similar symptoms. A mutation in the serine protease inhibitor, clade G, member 1 (SERPING1) gene is associated with HAE. Patients with HAE type I commonly carry either a small deletion within SERPING1 or a truncated transcript. We performed a multiplex ligation-dependent probe amplification (MLPA) assay on our indexed patient. Our result suggests a 2,009 bps deletion spanning across exons 5 and 6 within SERPING1. Although earlier literature has described other large DNA deletions encasing exons 5 and 6 in SERPING1, these DNA rearrangements were larger in size between 4 and 6 kbps, and the breakpoint locations were generally not determined due to technical constraints (Pappalardo et al., 2000; Duponchel et al., 2001; Roche et al., 2005; Loules et al., 2018; and Gößwein et al., 2008). Our report describes mapping of this 2,009 bps in SERPING1. Using a combination of molecular techniques, we were able to confirm and locate this large heterozygous genomic DNA deletion that includes both exons 5 and 6 of SERPING1.

Measuring natural killer cell cytotoxicity by flow cytometry.

Natural killer (NK) cell cytotoxic function is critical in guarding an organism against viral infections and malignantly transformed cells. Although the 51Chromium (51Cr)-release assay is regarded as the gold standard for assessing NK cell cytolytic activity, this method is associated with a number of technical problems including the use of radioactive reagents and inconsistent assay performance, due to the lack of assay standardisation across laboratories. Here we describe the setup of a flow cytometry (FC) based method for the measurement of NK cell cytotoxicity, suitable for patient testing. The FC protocol was assessed using four normal samples, and reference values for NK activity of the local Hong Kong population were defined by 40 peripheral blood samples from healthy volunteers. For method validation, we tested a total of 13 specimens including nine healthy individuals and four patients with clinical conditions that were expected to have NK cell dysfunction. We directly compared those results between FC and the 51Cr-release assay and we were able to demonstrate that FC is a clinically valid method for measuring NK cell function in a clinical setting.

Osteolipoma in the Forearm.

A case of left distal forearm and wrist osteolipoma in a 56 year old female is reported. The patient presented with a 3 year history of nontender left wrist mass. Radiographs demonstrated a lobulated mass of mixed low density and calcifications, not adjacent to and with no connection to underlying bone. Ultrasound showed a spheroid hyperechoic lesion with internal heterogeneity and rim of calcifications. Magnetic resonance imaging revealed a lesion with predominantly fat characteristics on T1 weighted and T2 weighted sequences, with rim of peripheral calcification and specks of internal calcification. Histological examination after excision of the mass showed the lesion to be an osteolipoma. Osteolipoma is a rare variant of lipoma with osseous metaplasia and should be considered in the differential of a fat containing mass with ossification.