Maleszewski, Joseph

Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by deficient levels and/or activity of glycosaminoglycan (GAG)-degradative enzymes. MPS are characterized by accumulation of the mucopolysaccharides heparan sulfate, dermatan sulfate, keratan sulfate, or chondroitin sulfate in tissues. We report the case of a 38-year-old woman with a history of joint restriction and retinitis pigmentosa who developed bivalvular heart failure requiring surgery. It was not until pathological examination of surgically excised valvular tissue that a diagnosis of MPS I was made. Her musculoskeletal and ophthalmologic symptoms, when placed in the context of MPS I, painted the diagnostic picture of a genetic syndrome that was overlooked until a diagnosis was made in late middle age.

Objective To investigate the aetiology and incidence of sudden cardiac arrest and death (SCA/D) in US competitive athletes. Methods Prospective surveillance was conducted from 1 July 2014 to 30 June 2018 through the National Center for Catastrophic Sports Injury Research in collaboration with national sports organisations. Autopsy reports, death certificates, and medical records were reviewed by an expert panel to determine aetiology. Athlete participation statistics from the National Federation of State High School Associations and the National Collegiate Athletic Association (NCAA) were used to calculate incidence rates per athlete-years (AY). Comparisons of incidence rates were calculated using incidence rate ratios (IRR) with 95% CIs. Results 331 cases of confirmed SCA/D (158 survivors; 173 fatalities) were identified; 15.4% in middle school, 61.6% in high school and 16.6% in college and professional athletes. Average age was 16.7 (11–29) years, and the majority were in male (83.7%), basketball (28.7%) or American football (25.4%) athletes. Common causes included hypertrophic cardiomyopathy (20.6%), idiopathic left ventricular hypertrophy (13.4%), coronary artery anomalies (12.0%) and autopsy-negative sudden unexplained death (9.6%). Coronary anomalies were more common in middle school athletes (28%), while cardiomyopathies (hypertrophic, arrhythmogenic, dilated, non-compaction or restricted) accounted for 47% of cases in college and professional athletes. Incidence was higher in male versus female athletes at the high school (1:43 932 AY (95% CI 1:38 101 to 1:50 907) vs 1:203 786 AY (95% CI 1:145 251 to 1:293 794); IRR 4.6 (95% CI 3.1 to 7.2)) and NCAA (1:34 906 AY (95% CI 1:25 385 to 1:49 173) vs 1:123 278 AY (95% CI 1:66 078 to 1:249 853); IRR 3.5 (95% CI 1.5 to 9.5)) levels. African American male NCAA Division I basketball players had the highest annual incidence rate of SCA/D (1:2087 AY (95% CI 1:1073 to 1:4 450)). Conclusions Cardiomyopathies account for nearly half of SCA/D cases in college and professional athletes, while coronary artery anomalies play a more prominent role than expected in middle school athletes. Over half of SCA cases in athletes result in sudden death, calling for improved prevention strategies.

Glycogen storage disease type IV (GSD IV, Andersen disease) is a rare autosomal recessive condition. The childhood neuromuscular subtype of GSD IV is characterised by a progressive skeletal myopathy with cardiomyopathy also reported in some individuals. We report a case of a 19-year-old man who presented with severe non-ischaemic dilated cardiomyopathy (NIDCM) necessitating heart transplantation, with biopsy showing aggregations of polyglucosan bodies in cardiac myocytes. He had no signs or symptoms of muscle weakness, liver dysfunction or neurologic involvement. A homozygous GBE1 c.607C>A (p.His203Asn) variant was identified. Our case is unusual in that our patient presented with an isolated NIDCM in the absence of other clinical manifestations of GSD IV. This case highlights the importance of considering storage disorders in young adults presenting with isolated NIDCM of unknown aetiology. It also emphasises the potential synergy between histopathological evaluation and genomic testing in enhancing diagnostic certainty.

Evidence of prior autoerotic asphyxia is often difficult to establish due to the decedent's efforts to hide the activity from others. In this case report, we suggest that a healed fracture of the thyroid cartilage is indicative of prior autoerotic asphyxia activity. The decedent was a 45-year-old man who was found unclothed on the floor of his bedroom with a belt ligature around the neck. A second rope ligature was loosely wrapped around the decedent's wrists, scrotum, and penis. A definitive escape mechanism was not identified, but a nearby towel and barbell weight may have comprised a possible escape mechanism. There was no known history of depression or prior autoerotic activity. Autopsy was notable for the presence of a healed fracture of the right superior horn of the thyroid cartilage. Three-dimensional (3D) surface scanning and 3D printing was utilized to preserve the anatomical findings prior to histologic sampling. To our knowledge, this is the first reported use of 3D surface scanning and 3D printing for the purpose of documenting a forensic finding prior to alteration of the anatomical specimen for histologic sampling. Acute fractures of the superior horns of the thyroid cartilage are not infrequently seen in ligature hanging. Therefore, the presence of a healed fracture in the setting of autoerotic asphyxia likely indicates prior activity. Histologic sampling of the laryngeal cartilages to detect occult healed fractures in autoerotic asphyxia may be useful. Three-dimensional scanning and printing may alleviate concerns for specimen alteration due to histology sampling.

An 88-year-old man with history of bioprosthetic aortic valve replacement was hospitalised with fever, chills, malaise and right lower extremity cellulitis. Laboratory investigations revealed leucocytosis and blood cultures grew Helcococcus kunzii. Although transoesophageal echocardiography was negative for endocarditis, the patient was treated with 4 week of intravenous ceftriaxone. However, he was readmitted 6 weeks later with symptoms of fever, chills and hypoxia in setting of recurrent H. kunzii bacteraemia. A repeat transoesophageal echocardiogram revealed a mobile mass on bioprosthetic aortic valve, severe perivalvular insufficiency with pseudoaneurysm formation, and severe native mitral and tricuspid valve regurgitation. Cardiothoracic surgery was consulted and the patient underwent replacement of aortic valve and aortic root, and tricuspid and mitral valve repairs. Histological examination of excised bioprosthetic aortic valve revealed active endocarditis with cocci identified on silver stain. Patient was successfully treated with 4-week course of intravenous ceftriaxone and was doing well at 2-year follow-up.