Endocrine Abstracts

Introduction: Mutations in SLC29A3 lead to PHID and H syndromes, familial Rosai Dorfman Disease and Histiocytosis-lymphadenopathy plus syndrome. PHID syndrome is associated with short stature, pubertal delay, endocrine and exocrine pancreatic insufficiency. We report a new association of PHID syndrome with severe systemic inflammation, scleroderma-like changes and cardiomyopathy.

Case report: A 12-year-old girl with PHID syndrome presented with shortness of breath, hepatosplenomegaly, lymphadenopathy, short stature, anaemia and ascites. ESR (110 mm/h), CRP (76 mg/l) and serum amyloid (SAA) levels were elevated. Prednisolone therapy provided some symptomatic relief however treatment with Anakinra (IL1 receptor antagonist) and Adalimumab (TNFα inhibitor) was ineffective. An echocardiogram showed biventricular myocardial hypertrophy and pericardial effusion. A cardiac MRI showed circumferential, epicardial, late gadolinium enhancement of the LV and RV myocardium, with sparing of the endocardial layer. This pattern is distinct from that usually caused by cardiac amyloidosis. No systemic amyloid deposits were observed on a whole body serum amyloid P scintigraphy (SAP) scan at the age of 10 years and normal urinary protein excretion further mitigated against renal amyloidosis. Abdominal ultrasound revealed large amounts of intra-abdominal fat surrounding the solid organs suggesting a possibility of evolving lipodystrophy with visceral adiposity.

Conclusion: PHID syndrome is a novel monogenic autoinflammatory syndrome (AIS) associated with severe elevation of SAA. Lipodystrophy, cutaneous sclerodermatous changes and cardiomyopathy were also present in this case. In contrast to other AIS, blockade of IL1 and TNFα was ineffective. The mechanism of severe autoinflammation is unknown, although nucleoside accumulation in macrophages could contribute to immune activation. It is important to further understand the mechanism of auto inflammation in PHID and related syndromes, since effective therapy so far has remained elusive.