BACKGROUND: McCune-Albright syndrome is a complex disorder encompassing multiple endocrinopathies. These manifestations are secondary to a mutation in the stimulatory G-protein alpha subunit. Cushing syndrome is due to autonomous secretory function of the adrenal gland and is present in 7.1% of patients with McCune-Albright syndrome. Cardiac newborn screenings assist in the identification of critical congenital heart disease. These screenings have become part of routine postnatal care nationwide.
METHODS: A 6-week-old Caucasian male presented to a cardiologist at the University of Tennessee Health Science Center with left ventricular hypertrophy and poor feeding after a failed cardiac newborn screen. He had been previously seen at 2 weeks by a cardiologist on follow-up for abnormal critical congenital heart disease screening. Electrocardiogram and echocardiographic studies identified hypertrophic cardiomyopathy. Other examination findings revealed multiple characteristic café-au-lait lesions along with hypotonia and rounded facies. Given his cardiac disease, he was admitted to the hospital, where an evaluation was done for Cushing syndrome, showing elevated cortisol by immunoassay of 38 μg/dL (1.7-14.0 μg/dL, Vitros 5600) after a dexamethasone suppression test and urinary cortisol elevated to 35 μg/dL/24 hours (reference range 3-9 μg/dL/24 hours) (Esoterix; Calabasas, CA). He was started on metyrapone therapy to block synthesis of cortisol. His cortisol improved and was suppressed less than 2 μg/dL. His hypertension and clinical features of Cushing syndrome improved.
CONCLUSIONS: This case demonstrates a unique presentation of Cushing syndrome in a young infant. This is the first case to our knowledge showing significant left ventricular hypertrophy resulting from Cushing syndrome identified following a failure on a critical congenital heart disease screen. It highlights the importance of considering of McCune-Albright syndrome in patients with Cushing syndrome, especially if other clinical features are present. Medical therapy can be used to treat Cushing syndrome and can result in improvement in the cardiovascular pathology.

UNASSIGNED: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder resulting from a mutation of alpha-galactosidase A gene (GLA), causing deficiency in alpha-galactosidase activity. The enzyme deficit can lead to storage of globotriaosylceramide in various organs including heart. Studies suggest that vasospastic angina (VSA) is associated with AFD.
UNASSIGNED: This clinical case series aimed to present two female patients with AFD, including progressive cardiac involvement: a 50-year-old woman (patient number 1) and a 39-year-old woman (patient number 2) who are siblings with a male AFD patient harbouring p. Arg342Glu missense variant in alpha-galactosidase A gene (GLA), who suffered VSA and subsequent ventricular fibrillation. Enzymatic tests and genetic analysis confirmed AFD in both female patients and histological tests revealed globotriaosylceramide deposits in their hearts. In patient number 1, a 12-lead electrocardiography and transthoracic echocardiography revealed cardiac hypertrophy. Coronary angiography revealed no organic coronary artery stenosis and vasospasms was induced by spasm provocation test. In patient number 2, no signs of cardiac hypertrophy were found, and coronary arteries had no organic stenosis with negative spasm provocation test. Both patients received enalapril therapy and enzyme replacement therapy (ERT).
UNASSIGNED: Different phenotype of AFD was occurred even with the same genetic variant in female heterozygote patients. The duration of exposing accumulation of Gb3 might affect cardiac hypertrophy and vasospasms. Coronary angiography with acetylcholine provocation test should be considered in female AFD patient, especially in case with cardiac hypertrophy.

BACKGROUND: Danon disease (DD) is a rare disorder characterized by cardiomyopathy, intellectual disability, and proximal myopathy. It is caused by mutations in the LAMP2 gene on X chromosome. Female patients most often present with late-onset cardiomyopathy and slow disease progression, but early-onset cases with unfavorable prognosis have been reported.
METHODS: We describe the clinical, pathological, and molecular features of a novel LAMP2 c.453delT mutation in a female patient with severe hypertrophic cardiomyopathy, Wolff Parkinson White (WPW) syndrome and rapid progression to heart failure, requiring heart transplant. Immunohistochemical analysis of LAMP2 in the explanted heart revealed a mosaic pattern of distribution, with discrete clusters of either stained or unstained cardiac myocytes, the latter being more frequent in the septum. These findings paralleled X chromosome inactivation within the myocardium. Interestingly, multiple foci of microscarring were found on histology in the Left Ventricle (LV) free wall and septum, in a close spatial relationship with remodeling and severe stenosis of intramural coronary arterioles.
CONCLUSIONS: Our findings suggest that several features may contribute to the early and severe cardiac phenotype in female DD patients. The type of mutation may account for the early disease onset, while both the inhomogeneous distribution of LAMP2 loss and the presence of microvascular remodeling may be determinant in the rapid progression to heart failure.

Information regarding the long-term outcome of enzyme replacement therapy (ERT) with recombinant human N-acetylgalactosamine 4-sulfatase (rhASB, galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.) for Taiwanese patients with mucopolysaccharidosis (MPS) VI is limited.
Nine Taiwanese patients with MPS VI (4 males and 5 females; age range, 1.4 to 21.1 years) treated with weekly intravenous infusions of galsulfase (1.0 mg/kg) in 5 medical centers in Taiwan were reviewed. A set of biochemical and clinical assessments were evaluated annually.
After 6.2 to 11.2 years of galsulfase treatment, 6 patients experienced improvement over baseline in the 6-minute walk test by a mean of 150 m (59% change over time), and 3 patients also increased the 3-minute stair climb test by a mean of 60 steps (46%). In a manual dexterity test, 3 patients decreased the time required to pick up 10 coins and put the coins into a cup by 15 s (33%). Shoulder range of motion in all 9 patients improved, and Joint Pain and Stiffness Questionnaire scores improved by 0.42 points (21%). Four patients showed improved pulmonary function. Five patients had positive effects on cardiac-wall diameters. Four patients had improved cardiac diastolic function. Liver and spleen sizes as measured by abdominal ultrasonography remained the same or decreased in all 9 patients. However, the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT. A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response.
Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI. This treatment reduced urinary GAG and had positive effects on a wide range of clinical functional assessments including endurance, mobility, joint function, pulmonary function, liver and spleen size, cardiac hypertrophy and diastolic dysfunction.