mucopolysaccharidoses ( mps ) are a group of rare inherited disorders characterized by abnormal accumulation of glycosaminoglycans ( gags ) in various tissues . a common feature of several of these disorders is cardiac involvement , which often includes anatomic and functional abnormalities of the heart valves . mps types i  ix each results from a deficiency of enzymes that are involved in the stepwise degradation of gags such as dermatan , keratan , heparin and chondroitin sulfates . mps iii comprises four related inborn errors of lysosomal degradation of heparan sulfate , known as mps iii types a , b , c , and d. all of them are characterized by progressive mental deterioration and behavioral problems , with only mild facial dysmorphism and mild somatic disease . the onset and severity of the disease are highly variable , but symptoms rarely appear during the first year of life . mps iii - a , or sanfilippo syndrome type a ( omim#252900 ) , arises when the activity of the enzyme n - sulfoglucosamine sulfohydrolase ( heparan n - sulfatase or sulfamidase ; ec 3.10.1.1 ) is lost . the sulfamidase gene ( sgsh;605270 ) is 11  kb long , comprises 8 exons , and is located on chromosome 17q25.3 . to date , around 140 different mutations associated with mps iii - a have been identified ( hgmd 2014 ) ( http://www.hgmd.org ) . cardiac compromise , including anatomical and functional abnormalities of the cardiac valves , myocardial hypertrophy , thickened chordae tendineae , and narrowing of the coronary arteries , develops in most patients with mps , , , , . involvement of the mitral valve , often associated with an aortic valve anomaly and/or left ventricular hypertrophy , is the most common presentation . cardiomyopathy has been reported in mps i and vi , , . however , cardiac involvement in mps iii is generally mild , . we report a case of a patient with mps iii - a who presented cardiac symptoms in the first year of life , ultimately requiring mitral valve replacement surgery in childhood . a 6-month - old girl was admitted to a tertiary public children 's hospital in northeast brazil for evaluation of signs and symptoms of cardiac insufficiency . the weight and length at birth were 2900  g and 49  cm respectively . according to her mother , the patient had exhibited cyanosis since age 1  month . the patient responded to medical therapy and was lost to follow - up until age 6  years , when she returned with anasarca and pneumonia . on physical examination , she had coarse facial features , with thick hair , a low hairline , thick eyebrows with synophrys , a wide and flat nasal bridge , thick lips and full cheeks ; generalized hirsutism ; short neck ; a cardiac murmur ; and hepatosplenomegaly . an echocardiogram showed dilated cardiomyopathy , rupture of the mitral chordae tendineae , severe mitral insufficiency , and mild tricuspid insufficiency . a ct scan of the chest revealed right apical pneumonia and left atelectasis in the lingula . the diagnosis of mps was confirmed by increased urinary excretion of heparan sulfate and deficient sulfamidase activity on leukocytes . the patient underwent cardiac surgery for mitral valve repair ( placement of biological prosthesis ) , which was completed successfully with an uneventful postoperative course . genomic dna was extracted from peripheral blood sample using a standard salting - out procedure  . all coding exons of sgsh gene and intron - exon boundaries were amplified by polymerase chain reaction ( pcr ) as per beesley et al . . pcr fragments were sequenced using a standard protocol and submitted to capillary electrophoresis on a 3500 applied biosystems dna analyzer . cdna and protein numbering were based on the reference sequences nm_000199.3 and the nomenclature used for reporting sequence variants was according to . after bidirectional sequencing of all exons of the sgsh gene , we were able to identify three different alterations in homozygosis : c.239  g  >  t ( p.g80v ) , c.1337 a  >  g ( p.h446r ) and c.524  t  >  c ( p.y174y ) . these variants have not been previously described in the single nucleotide polymorphism database ( dbsnp ; http://www.ncbi.nlm.nih.gov/ ) and the human gene mutation database ( hgmd ) ( http://www.hgmd.org ) . according to polyphen ( http://genetics.bwh.harvard.edu/pph2/ ) algorithm  , c.239 g  >  t ( p.g80v ) is predicted to be probably damaging , with a score of 1.00 , and c.1337 a  >  g ( p.h446r ) is predicted to be a benign mutation , with a score of 0 . genomic dna was extracted from peripheral blood sample using a standard salting - out procedure  . all coding exons of sgsh gene and intron - exon boundaries were amplified by polymerase chain reaction ( pcr ) as per beesley et al . . pcr fragments were sequenced using a standard protocol and submitted to capillary electrophoresis on a 3500 applied biosystems dna analyzer . cdna and protein numbering were based on the reference sequences nm_000199.3 and the nomenclature used for reporting sequence variants was according to . after bidirectional sequencing of all exons of the sgsh gene , we were able to identify three different alterations in homozygosis : c.239  g  >  t ( p.g80v ) , c.1337 a  >  g ( p.h446r ) and c.524  t  >  c ( p.y174y ) . these variants have not been previously described in the single nucleotide polymorphism database ( dbsnp ; http://www.ncbi.nlm.nih.gov/ ) and the human gene mutation database ( hgmd ) ( http://www.hgmd.org ) . according to polyphen ( http://genetics.bwh.harvard.edu/pph2/ ) algorithm  , c.239 g  >  t ( p.g80v ) is predicted to be probably damaging , with a score of 1.00 , and c.1337 a  >  g ( p.h446r ) is predicted to be a benign mutation , with a score of 0 . cardiac involvement is detected early in life in more than half of all patients identified as having mps , but it is rarely the first presenting feature of mps iii , as the case presented herein . cardiomyopathy and cardiac valve insufficiency develop as gag accumulates in the myocardium , expands the spongiosa of the cardiac valves , and proliferates within the myointima of the epicardial coronary arteries . in the most severe cases of mps i and mps vi , congestive heart failure and death occur in the first decade of life , , , , . in mps iii , however , severe cardiac manifestations are extremely rare , although a report of cardiomyopathy in a 53-year - old patient with mps iii - a patient has been published in the literature . besides that , in one patient with severe mitral valve stenosis , the detection of unexplained hepatomegaly led to further metabolic studies and , ultimately , a diagnosis of mps iii - a . in another case of mps iii - c , studied 57 cases of mps regarding cardiac symptoms , and found that only four had such symptoms as the presenting feature ( mps i , age 1.2  years ; mps ii , age 3  years ; mps iii , age 9  years ; mps iv , age 0.3  years ) . in the case presented herein , there was no initial suspicion of mps during the first year of life because the patient did not exhibit dysmorphic features or neurological impairment . in the literature , there are few cases of mps iii in which developmental delay was noted from birth ; in the majority of cases , symptoms were first noted at a median age of 2.5  years , and consisted of developmental delay and/or behavioral problems  , . dangel   examined 20 patients with mps iii and found that 50% had a normal echocardiogram , but one 8-year - old girl had congestive cardiomyopathy with severely impaired left ventricular function . phenotype association as the pathogenic mutation described here is novel , we are not able to predict if this is associated with a higher risk of development of cardiac disease . we propose that mps , including mps iii - a , should be suspected and added to the differential diagnosis of all patients presenting with cardiomyopathy during the first year of life , even without somatic feature characteristic of mps . we do not know whether severe cardiac involvement in mps iii - a is rare or simply underdiagnosed . however , the finding that mps iii is also associated with secondary storage of dermatan sulfate   suggests that other organs , in addition to those of the nervous central system , can be severely affected by this disorder . furthermore , the rapidly lethal course of cardiomyopathy may hinder diagnostic investigation of mps in affected patients . erlane marques ribeiro , ida vanessa schwartz , ana carolina brusius - facchin , sandra leistner - segal and carlos antnio bruno da silva declare that they have no conflicts of interest . all procedures were conducted in accordance with the ethical standards of the institutional and national committees on human experimentation and with the 1975 declaration of helsinki , as revised in 2000 .
severe cardiac involvement is a common feature of mucopolysaccharidoses ( mps ) , but occurs only rarely in mps iii ( sanfilippo syndrome ) . 
 we report herein a case of mps iii - a having cardiac involvement as its first manifestation . 
 analysis of the sgsh gene showed homozygosity for the novel mutation p.g80v . 
 we propose that mps disorders , including mps iii - a , should be included in the differential diagnosis of every case of cardiomyopathy presenting during the first year of life .