Two cases of pulmonary hypertension associated with type III glycogen storage disease

Abstract

Glycogen storage diseases (GSDs) comprise alarge, heterogeneous group of disorders characterized byabnormal glycogen deposition. Multiple cases in the literaturehave demonstrated an association between GSD type Iand pulmonary arterial hypertension (PAH). We now alsoreport on two patients with GSD type III and PAH, a novelassociation. The first patient was a 16-year-old girl of Nicaraguandescent with a history of hepatomegaly and growthretardation. Molecular testing identified a homozygous17delAG mutation in AGL consistent with GSD type IIIb.At the age of 16, she was found to have PAH and was startedon medical therapy. Two years later, she developed acutechest pain and died shortly thereafter. The second patient is a13-year-old girl of Colombian descent homozygous for thec.3911dupA mutation consistent with GSD IIIa. An echocardiogramat age 2 showed left ventricular hypertrophy, whichresolved following the institution of a high protein, moderatecarbohydrate diet during the day and continuous gastric-tubefeeding overnight. At the age of 12, she was found to havepulmonary hypertension. She was started on sildenafil, andher clinical status has shown marked improvement includingnormalization of her elevated transaminases. PAH may be arare association in patients with GSD IIIa and IIIb andshould be evaluated with screening echocardiograms forcardiac hypertrophy or if they present with symptoms ofright-sided heart failure such as shortness of breath, chestpain, cyanosis, fatigue, dizziness, syncope, or edema. Earlydiagnosis of PAH is important as increasingly effectivetreatments are now available.