• Journal of The Korean Society of Inherited Metabolic disease
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• v.13 no.2
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• pp.111-119
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• 2013

Purpose: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by deficiency of the enzyme ${\alpha}$-L-iduronidase, which leads to a broad spectrum of multisystemic manifestations. Short stature and decreased growth velocity are prominent features of MPS I. The aim of the present study was to evaluate the effect of enzyme replacement therapy (ERT) on growth of Korean MPS I patients from a single center. Methods: Height data were obtained by retrospective chart review of 10 Korean patients with MPS I who had received ERT for a minimum of 3 years. Height was expressed as standard deviation scores (SDS) based on normative data. Annual growth rates were calculated before and during ERT. A piecewise regression model was used to analyze height z-scores before and after treatment. Individual analysis was performed for impact of phenotype [(severe (Hurler) versus attenuated (Hurler-Scheie, Scheie)] on growth. Results: Annual growth was 3.3 cm (z-score= -0.21) in the year before ERT and 6.2 cm (z-score= 0.17), 5.8 cm (z-score= 0.07), and 3.8 cm (z-score= -0.4) in the first, second, and third years of ERT, respectively. Regression analysis showed improvement in the slope after ERT (difference= 0.04; P=0.022). Estimated slope differences between severe and attenuated phenotypes were statistically significant before (P=0.001) and after treatment (P<0.0001), although no significant difference was noted when stratified by phenotype. Conclusion: ERT with aldurazyme appears to have a positive impact on linear growth in patients with MPS I.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.19 no.1
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• pp.1-11
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• 2019

Purpose: Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. The purpose of the present study was to determine the incidence of CH in South Korea during the period from January 1991 to March 2004. Methods: Central data from each city branch of SCL (Seoul Clinical Reference Laboratories) in Yongin, South Korea, was gathered and collectively analyzed. Newborn screening (NBS) for CH was based on measuring the levels of neonatal thyroid stimulating hormone (TSH) and free T4 (a cut-off of 20 mIU/L and less than 0.8 ng/dL, respectively). Results: During the study period, 671,805 live births were screened for CH based on TSH and free T4 ELISA assays. A total of 159 newborns were deemed positive for CH out of 671,805, with a corresponding incidence of 1 in 4,225. When a cut-off of 20 mIU/L was used in TSH assays, the associated sensitivity, specificity, and positive predictive values (PPV) were 100.0%, 99.7%, and 10.8%, respectively. When a cut-off of 0.8 ng/dL in free T4 assays was used, the associated sensitivity, specificity, and PPV were 100.0%, 98.5%, and 3.9%, respectively. Conclusion: CH incidence in South Korea as evidenced by the results of NBS was compared with its incidence and comparable to the other countries prior to 2004.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.2
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• pp.58-62
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• 2022

Pompe disease (PD) is an autosomal recessive genetic disorder caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA). It is easy to hastily diagnose as patients if they have two pathogenic variants. Clinical pathologists misdiagnosed our infant and her mother as PD. Here, we report a case of pseudodeficiency in a potential late-onset Pompe disease (LOPD) carrier with a double dual variant, each in cis formation in a 3-month infant. The person who has two pathogenic variants was diagnosed as a carrier, not a patient. It was first reported in Korea. The patient had: two likely pathogenic heterozygous mutations on exon #4: c.752C>T (p.Ser251Leu), c.761C>T (p.Ser254Leu), and a heterozygous mutation on exon #12: c.1726G>A (p.Gly576Ser), also with a heterozygous mutation on exon #15: c.2065G>A (p.Glu689Lys). By presenting this case we emphasize the possibility of cis formation of genes which may cause pseudodeficiency, and potential LOPD carrier form. Hereby we suggest that thorough evaluation of GAA gene is essential among whom initially diagnosed as PD.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.1
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• pp.25-30
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• 2023

Leigh syndrome is a rare progressive neurodegenerative mitochondrial disorder with clinical and genetic heterogeneity. Recently, balletic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes from Leigh and West syndrome to a rare syndrome CAGSSS characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome (OMIM#616007). We describe a child with Korean Leigh syndrome with urologic manifestations resulting from a compound heterozygote mutation in IARS2. A 5-year-old girl visited the emergency room with a complaint of abdominal pain accompanied by abdominal distension. Abdominal-pelvic CT showed a markedly distended urinary bladder without definite obstructive lesions. She was diagnosed with neurogenic bladder dysfunction based on a urodynamic study. She had global delayed development due to neurologic regression after 6 months of age and a history of bilateral cataract surgery at the age of 2 years. Her brain magnetic resonance imaging showed symmetrically increased signal intensities in the bilateral putamen and caudate nuclei with diffuse cerebral atrophy. No gene variants were identified through whole-mitochondrial genome analysis. Whole exome sequencing was performed for diagnosis, and compound heterozygous pathogenic variants were identified in IARS2: c.2446C>T (p. Arg816Ter) and c.2450G>A (p. Arg817His). To the best of our knowledge, this is the first case report of bladder dysfunction manifestation in a patient with IARS2-related Leigh syndrome. Thus, it broadens the clinical and genetic spectrum of IARS2-associated diseases.