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Atypical Presentation of Mucopolysaccharidosis. Morquio's Students Corner Case Report Atypical Presentation of Mucopolysaccharidosis. Morquio’s Syndrome (Type IV-B): A Morbid Entity Mehwish Farrukh1, Ayesha Haque2 Abstract Mucopolysaccharidosis (MPS) are a group of metabolic disorders of the lysosomal storage disease family caused by the absence or malfunctioning of lysosomal enzymes, which blocks degradation of mucopolysaccharides and leads to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate. Morquio’s syndrome is a rare autosomal-recessive mucopolysaccharidosis. This syn- drome is characterized by a reduced activity of N-acetylgalactosamine-6-sulfate-sulfatase (type A), or beta-galactosidase (type B). This deficiency leads to a lysosomal storage disease with accumulation of keratan sulfate and chondroitin-6-sulfate in connective tissue, skeletal system and teeth. The gen- eral phenotype includes coarse facies, corneal clouding, hepatosplenomegaly, joint stiffness, hernias, dysostosis multiplex, lower limb alignment problems, mucopolysaccharides excretion in the urine and metachromatic staining in peripheral leukocytes and bone marrow. Consequently, aortic valvular dis- ease, gastrointestinal disease and dental abnormalities occur. Clinical manifestations of mucopoly- saccharidosis depend on the type of disease. We report a case of morquio’s syndrome in a child, solely diagnosed on the basis of history and physical examination of the case reported. The clinical features and complications of the case and review of the literature are discussed. Keywords: Mucopolysaccharidosis, connective tissue, morquio’s syndrome, lysosomal storage dis- ease. (ASH & KMDC 19(2):109;2014). Introduction tendons, cornea, skin and connective tissue. People with MPS either do not produce enough of Mucopolysaccharidosis (MPS) are hereditary one of the 11 enzymes required to break down group of broad spectrum metabolic disorders due to these sugar chains into proteins and simpler mol- deficiency or mutations of genes coding for lysoso- ecules, or they produce enzymes that do not work mal enzymes required to degrade a class of gly- properly2. Over time, these GAG’s collect in the cosaminoglycans (acid mucopolysaccharides). Gly- cells, blood and connective tissues. This results in cosaminoglycans (GAG’s) are a long-chain com- permanent, progressive cellular damage which af- plex carbohydrate composed of uronic acids, amino fects the appearance, physical abilities, organ and sugars, and neutral sugars. The major GAGs are system functioning and, in most cases, mental de- chondroitin-4-sulfate, chondroitin-6-sulfate, heparan velopment. sulfate, dermatan sulfate, keratan sulfate, and 1 ______________________________________________________________________________________________hyaluronan . GAG’s help to build bone, cartilage, On the basis of clinical and biochemical stud- 1Final year Medical Student ies, these disorders have been designated as MPS 2Postgraduate Medical Student Paediatric Unit II, Abbasi Shaheed Hospital, I through MPS VII. They are classified into Hurler’s Karachi Medical and Dental College syndrome (MPS I-H), Scheie’s syndrome (MPS I- S), Hurler-Scheie’s syndrome (MPS I-H/S), Hunter’s Correspondence: Mehwish Farrukh syndrome A, B (MPS II-A, B), Sanfilippo’s syn- Paediatric Unit II, Abbasi Shaheed Hospital, Karachi Medical and Dental College, drome A,B,C,D (MPS II-A,B,C,D), Morquio’s syn- North Nazimabad, Karachi drome A,B,C (MPS IV-A,B,C), Maroteaux-Lamy’s Email: [email protected] 109 Annals Abbasi Shaheed Hospital & Karachi Medical & Dental College Mehwish Farrukh, Ayesha Haque syndrome (MPS VI) and Sly’s syndrome MPS VII)3. via spontaneous vaginal delivery. There is no history The mucopolysaccharidosis incidence is around of maternal illness or drug exposure or premature 0.04-0.3% of the newborn and they are 1.5% of all rupture of membranes. He was vaccinated accord- congenital disorders4. The general phenotype in- ing to EPI schedule. There was no developmental cludes facial dysmorphism, corneal clouding, delay of milestone to this date. hepatosplenomegaly, joint stiffness, hernias, dysos- On general examination, an active and respon- tosis multiplex, contractures, pulmonary dysfuction, sive boy with occipito-frontal circumference between myocardial enlargement, valvular dysfunction, neuro- 60th and 70th centile, weight and length below 5th logical involvement and mucopolysaccharides excre- centile, temperature 100°F, respiratory rate 18/min, tion in the urine and metachromatic staining in heart rate 100 beats/min. Child had a semi-crouch- peripheral leukocytes and bone marrow1,5-6. ing stance and appeared small for age with dispro- Mucopolysaccharidosis type IV (MPS IV) re- portionate dwarfism, thoracic deformity and a short sults from an inborn deficiency of lysosomal en- neck. The dental enamel was defective, nose was zyme N-acetyl-galactosamine-6-sulphate sulphatase stubby, the mouth broad and teeth widely spaced. (type A) beta-galactosidase (type B), an enzyme His hands were mis-shapen and loose-jointed; nev- that degrade karatansulphate. The syndrome is es- ertheless his features were not ugly. timated to occur in 1 of every 200,000 births4. We Chest was clear on auscultation; his liver and present this rare case of MPS (Morquio’s syn- spleen were not palpable. On more detailed exami- drome) type IV B that came to Out Patients De- nation main signs of bone deformities namely pec- partment of Paediatrics Unit II, Abbasi Shaheed tus carinatum, ligamentous laxity, atlanto axial Hospital. The child had the atypical features of instability, flat feet as shown in Fig. 1 & 2 were skeletal deformities short neck, pectus carinatum, present. Joints were very loose and hyper-mobile no corneal clouding, normal intelligence and all with early flattening of the growth curve, leading rap- other features suggestive of MPS type IV. idly to almost complete growth arrest. Case Report Patient has normal cognitive development. Bone scan revealed that skull with reduced bone A nine-year-old boy (84cm, 16kg) presented at density, prominent maxilla, short vertical height of the Out-Patients Department of Paediatrics Unit II, cervical vertebra, increased AP diameter of chest, Abbasi Shaheed Hospital with the complaint of fail- dorsolumbar lordosis, ovoid vertebral bodies with ure to gain weight, and abnormal shape of bones in- central anterior beaking, widened intervertebral disc cluding spine. In early infancy it was noticed by spaces, narrow pelvis, hypoplastic acetabulum with parents that he had an abnormal shaped chest, broad flared iliac wings. Limbs showed short radius broad ribs, and with age child did not grow and was with hypoplastic ends of radius and ulna and hu- of a small stature. During early childhood the skel- merus as shown in Fig. 3 & 4, widening of femoral etal deformities became increasingly evident and he neck with coax valga, proximal pointing and short- walked with difficulty. However, his mental status re- ening of metacarpal and metatarsal phalanges. mained normal. Mother said that the child could see well and had no problems in the vision. On laboratory investigations the complete blood picture, serum calcium, phosphorus, alkaline phos- He had never visited a general practitioner or phatase and all other bio-chemical markers were in local hospital for any other complaints. He has the normal range for age. three siblings, none of which had a congenital or similar illness however; his first cousin suffers from a similar congenital disease. His parents were mar- ried in consanguinity. He was delivered at full term Volume No. 19 (2), December 2014 110 Atypical Presentation of Mucopolysaccharidosis. Morquio’s Syndrome (Type IV-B): A Morbid Entity Discussion Patient suffering of MPS, usually, don’t show clinical sign from their birth in fact the signs de- The eponym Morquio’s syndrome velop gradually, later in life with characteristic (mucopolysaccharidosis type IV; MPS IV) is a rare appearence2. Genu valgum and paraplegia of slow autosomal-recessive mucopolysaccharidosis that onset due to spinal cord compression are common exists in two forms (Morquio syndromes A and B) complications which may bring children with the and occurs because of a deficiency of the enzymes true Morquio’s syndrome4.The average survival of N-acetyl-galactosamine-6-sulfatase and beta-galac- these patients is around 20-30 years5, and the exi- tosidase, respectively6. A deficiency of either en- tus is due to cardiac failure or to infections to the zyme leads to an abnormal accumulation of certain gastrointestinal tract or to instability of atlantoaxial 8 complex carbohydrates (mucopolysaccharides or joint . glycosaminoglycans) in the arteries, skeleton, All mucopolysaccharidosis are autosomal re- eyes, joints, ears, skin, and/or teeth. These accu- cessive disorders, except for Hunter’s syndrome mulations may also be found in the respiratory sys- that is X-linked and recessive form9. Genetic coun- tem, liver, spleen, central nervous system, blood, seling is important in this autosomal recessive dis- bone marrow and eventually causes progressive order and enzymatic and/or molecular testing can damage to cells, tissues, and various organ sys- be offered for prenatal diagnosis. Although no rou- tems of the body. In most cases, individuals with tine laboratory findings are present in MPS. The di- Morquio syndrome have normal intelligence, as in agnosis is suggested by elevated urinary GAG’s level and profile, and is confirmed by GALNS enzy- our patient. matic studies on molecular
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