Ann Lab Med.  2013 Jan;33(1):75-79. 10.3343/alm.2013.33.1.75.

The First Korean Case of Mucopolysaccharidosis IIIC (Sanfilippo Syndrome Type C) Confirmed by Biochemical and Molecular Investigation

• Huh HJ
• Seo JY
• Cho SY
• Ki CS
• Lee SY
• Kim JW
• Park HD
• Jin DK

• KMID: 1781302
• DOI: http://doi.org/10.3343/alm.2013.33.1.75

Abstract

Mucopolysaccharidosis (MPS) III has 4 enzymatically distinct forms (A, B, C, and D), and MPS IIIC, also known as Sanfilippo C syndrome, is an autosomal recessive lysosomal storage disease caused by a deficiency of heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase (HGSNAT). Here, we report a case of MPS IIIC that was confirmed by molecular genetic analysis. The patient was a 2-yr-old girl presenting with skeletal deformity, hepatomegaly, and delayed motor development. Urinary excretion of glycosaminoglycan (GAG) was markedly elevated (984.4 mg GAG/g creatinine) compared with the age-specific reference range (<175 mg GAG/g creatinine), and a strong band of heparan sulfate was recognized on performing thin layer chromatography. HGSNAT enzyme activity in leukocytes was 0.7 nmol/17 hr/mg protein, which was significantly lower than the reference range (8.6-32 nmol/17 hr/mg protein). PCR and direct sequencing of the HGSNAT gene showed 2 mutations: c.234+1G>A (IVS2+1G>A) and c.1150C>T (p.Arg384*). To the best of our knowledge, this is the first case of MPS IIIC to be confirmed by clinical, biochemical, and molecular genetic findings in Korea.

Keyword

Mucopolysaccharidosis IIIC; HGSNAT; Sanfilippo syndrome; Korea

MeSH Terms

Acetyltransferases/*genetics
Asian Continental Ancestry Group/*genetics
Base Sequence
Child, Preschool
Chromatography, Thin Layer
Female
Glycosaminoglycans/urine
Heparitin Sulfate/chemistry/metabolism
Humans
Leukocytes/immunology/metabolism
Mucopolysaccharidosis III/*diagnosis/genetics/radiography
Mutation
Republic of Korea
Sequence Analysis, DNA
Glycosaminoglycans
Heparitin Sulfate
Acetyltransferases

Figure

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  Fig. 1 Radiographic findings. (A) Lateral view of the spine showing vertebral dysplasia, with ovoid or round vertebral bodies. (B) Posteroanterior views of the hand and wrist showing widening of the metacarpals and the proximal ends of the phalanges.

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  Fig. 2 Direct sequencing of the HGSNAT gene. The patient was a compound heterozygote for c.234+1G>A and c.1150C>T (p.Arg384*).Abbreviation: HGSNAT, heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase.

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