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PRENATAL DIAGNOSIS OF MAROTEAUX - LAMY SYNDROME

BN Apte, Suvarna Bhingarde
Department of Human Genetics, Bombay Hospital Trust, Mumbai 400 020.


A couple with a child having genetic disease has a dilemma - whether to take another chance. The availability of prenatal diagnosis enables one to prevent the recurrence of the same disease in the family.

We present here a case of Maroteaux - Lamy Syndrome (Mucopolysaccharidosis VI or MPS VI) which was prenatally diagnosed.

 

INTRODUCTION

Mucopolysaccharidoses is hereditary having insidious onset and a progressive course. Mucopolysaccharides (MPS) are found in the ground substance of the connective tissue. There are four major mucopolysaccharides - chondroitin sulphate, dermatan sulphate, heparan sulphate and keratan sulphate.

A large number of enzymes are involved in the degradation of MPS in a temporal sequence. A reduced or absent enzyme activity results in the accumulation of MPS. The classification of MPS, the mucopolysaccharides excreted in urine and the enzyme involved in their degradation are shown in Table 1.

TABLE 1
Classification of mucopolysaccharidoses
Syndrome MPS Designation Compound stored Excreted Defective Enzyme
Hurler IH Dermatan sulphate, heparan sulphate Alpha-L-Iduronidase
Scheie Is Dermatan sulphate, Alpha-L-Iduronidase
Hunter II Dermatan sulphate , heparan sulphate Iduronotesulphate sulphatase
Sanfilippo type A IIIA Heparan sulphate Heparan-S- (sulphaminidase)
Sanfilippo type B IIIB Heparan sulphate N-acetyl-alpha-D- glucosaminidase
Sanfilippo type C IIIC Heparan sulphate N-acetyl-alpha-D glucosaminidase
Sanfilippo type D IIID Heparan sulphate N-acetyl-alpha-D glucosaminidae-6-sulphatase
Morquio A IVA Kertan sulphate Galactosamine-6-sulphate sulphatase
Morquio B IV B Kertan sulphate Beta-galactosidase
Maroteaux-Lamy VI Dermatan sulphate N-acetylgalacto-samine-4-sulphatase (arylsulphatase B)
Sly VII Dermatan sulphate heparan sulphate, chondroitin 4,6 sulphate Beta-glucuronidase

 


As a group, all patients with MPS appear alike, except those with Sanfilippo syndrome (MPS III). They have coarse facial and somatic features, umbilical and scrotal hernia, macroglossia, visceromegaly, disostosis multiplex and joint involvement. In most forms corneal cloudiness is seen. These symptoms usually appear during early infancy. Patients with MPS III are mentally retarded with severe hirsutism and synophrys. All mucopolysaccharidoses are inherited as autosomal recessive except for the Hunter syndrome (MPS II) which is an x linked disease.

CASE REPORT

Mrs. SL, 30 years old came to our department with a bad obstetric history - an abortion at two months of gestation and a death of a baby girl, five days after birth. The baby had multiple congenital anomalies and the cause of death was cardiorespiratory arrest. No investigations were carried out. Mrs. SL had conceived again after six years and was twenty weeks pregnant. Sonography done on the foetus showed foetal spine consistently with abnormal curvature. Foetal abdominal shadow was also not well visualised (Fig. 1).

We had no proband to go by. We decided to carry out electrophoretic analysis of the amniotic fluid for MPS. [8] , [9] The analysis showed a strong band in the region of dermatan sulphate (Fig. 2). We, therefore, decided to carry out quantitative estimation of arylsulphatase B in the amniotic fluid which is more specific.[10] The results of these measurement are shown in Table 2. The activity of arylsulphatase B was significantly low Two more normal amniotic fluid samples assayed for the enzyme gave values well within the normal limits. An additional enzyme assay of beta-galactosidase done on all the three samples as control gave normal values.

Fig 1 : Sonogram kyphoscoliotic in the foetus
Fig 1 : Sonogram kyphoscoliotic in the foetus
 
Fig 2 : Illustration of agarose get electrophoresis
Fig 2 : Illustration of agarose gel electrophoresis of
A) The amniotic fluid sample
B) Dermatian sulphate as standard

 

This confirmed the diagnosis of MPS VI in this unborn patient.

DISCUSSION

MPS VI is transmitted as an autosomal recessive trait. Siblings with multiple defects and their normal parents have been observed in a number of families. Consanguinity has been documented. The gene for the enzyme arylsulphatase B, is located on chromosome 5. [10] The disorder is diagnosable prenatally. Heterozygosity may be demonstrated by assay of arysulphatase B. [11] , [12]

Surgical corrective procedure may be useful in the management of deformities of the hips and cornea. Bone marrow transplantation in a 13 year old patient has shown marked regression and correction of almost all the clinical manifestation of the disease. This, therefore, offer the only hope as a form of therapy.

ACKNOWLEDGEMENT

We are thankful to our Medical Director for allowing us to publish this paper. We are also thankful to Miss. Maria Gracious for preparing this manuscript and to Mr. Suryakant Shejwal for laboratory assistance.

REFERENCES

1.Brante G Gorgoylism. A mucopolysaccharidosis. Scand J Clin Lab Invest 1952; 4 : 43-52.

2.Mckusick VA. Genetic nosology - three approaches. Am J Hum Genet 1978; 30 : 105-12.

3.Roden L. Structure and metabolism of connective tissue proteoglycans in Lennarz, WJ (ed) : The biochemistry of glycoproteins and proteoglycans, New York, Plenum Press, 1980; 267-302.

4.Mukusick VA. Heritable disorders of connective tissue, IVth ed. St. Louis, Mosby, 1972; 611-27.

5.Dorfman A, Matalon R. The mucopolysaccharidoses, in The metabolic basis of inherited disease, IIIrd ed., Stanbury JB, Wyngaarden JB, Fredrickson DS, McGraw - Hill, New York, 1972; 1218.

6.Mckusick VA, Kaplan D, Wise D, Hanley WB, Siddarth SB, Sevick ME, Maumenee AE. The genetic mucopolysaccharidoses, Medicine, 1965; 44 : 445-83.

7.Al-Essa MA, Ozand PT. In manual of metabolic diseases, scientific publications office, 1998, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.

8.Varley H, Gowenlock AH, Bell M. Separative procedures. Electrophoresis in practical clinical biochemistry, Vol. I, Vth ed. William Heinemann Medical Books Ltd., London, 1984; 76-102.

9.Apte BN, Bhingarde S. Manuscript in preparation.

10.Galjaard H. Genetic metabolic diseases elsevier/North Holland Biomedical Press, 1980; 816-7.

11.Shapira E, De Gregorio RP, Malaton R, Nadler HL. Reduced arysulphatase B activity of the mutant enzyme protein in maroteaux - Lamy Syndrome, Biochem. Biophys Res Commun 1975; 62 : 448-53.

12.Van Dyke DL, Fluharty AL, Schafer IA, Shapiro LJ, Kihara H, Weiss L. Prenatal diagnosis of Maroteaux - Lamy Syndrome. Am J Med Genet 1981; 8 : 235-40.

13. Krivit W, Pierpont ME, Ayaz K, Tsai M, Ramsay NKC, Kersey JH, Weisdorf SL, Sibley R, Snover D, McGovern MM, Schawrtz MF, Desnick RJ. Bone marrow transplantation in the maroteaux - Lamy Syndrome (Mucopolysaccharidosis type VI). Biochemical and clinical status 24 months after transplantation. N Engl J Med 1984; 311 : 1606.

 

 


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