• Clinical and Experimental Pediatrics
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• 제50권3호
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• pp.315-318
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• 2007

본 증례 보고는 작은 키와 단지증을 가진 전형적인 Joubert Syndrome 환아의 10년간 장기 추적 관찰한 결과이다. 환아는 영아기 초기부터 저호흡이 동반된 빈호흡, 율동성 안구 운동, 근긴장저하를 보였다. 생후 5개월에 Joubert Syndrome의 임상 증상과 전형적 MRI 소견을 보여 진단되었다. 비정상 호흡과 안구 운동은 4세경에 사라졌다. 두위는 정상 범위를 유지하였으나 키와 몸무게는 뚜렷히 정체되었다. 단순 방사선 소견 상 뇌압 상승 소견이 있는 커진 두개골과 안면골의 저형성, 손과 발의 비정상적 연골 형성을 보였다. 본 증례는 말초 이골증이 있는 Joubert Syndrome의 첫번째 보고이다.

• 대한유전성대사질환학회지
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• 제15권3호
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• pp.118-126
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• 2015

Background and objectives: A deficiency of BH4 (tetrahydrobiopterin) not only causes the classical phenylketonuric phenotype, but also is the source of neurological signs and symptoms due to impaired syntheses of L-Dopa and serotonin. The treatment of BH4 deficiency usually consists of replacement with BH4 and the neurotransmitters. We performed this study to finding out long-term follow-up clinical symptoms and prognosis of BH4 deficiency. Methods: Clinical and biochemical, genetic analysis were done retrospectively from January 1999 to July 2015 in Soonchunhyang University Hospital. Results: In our study, total 207 patients were confirmed to hyperphenylalaninemia. Among them, 10 patients were BH4 deficiency. 9 patients were 6-pyruvoyl-tetrahydropterin (PTPS) deficiency and one patient was dihydropteridine reductase (DHPR) deficiency. The patients who received delayed treatment, most of our patients suffered from severe psychomotor retardation, hypotonia and seizure. c.259C>T mutation was identified most commonly in PTPS gene analysis. A patient with DHPR deficiency had a mental retardation, dystonia, seizure. His seizure semiology was dialeptic feature. His EEG showed generalized spike wave patterns. All patients had treated with tolerate L-Dopa, BH4 and 5-hydroxytryptophan. Most of the early treated patients have a good tolerance for drugs well. But some patients had neurologic symptoms, despite early detection and treatment. Conclusion: BH4 deficiency patients who had delayed treatment tend to have severe psychomotor problem and neurologic deficits.

• 대한유전성대사질환학회지
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• 제11권1호
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• pp.88-98
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• 2011

Lesch-Nyhan syndrome is a X-linked recessive disorder caused by a deficiency of the enzyme hypoxanthine-guanidine phosphoribosyltransferase (HPRT), enzyme to recycle purines. Case history: born induced vaginal delivery at 40 weeks complicated by premature membrane ruputure, body weight 2.820 gm. He showed failure to thrive showing severe protein aversion like milk products and pink daper. Developmental delay revealing rolling over at 10.5 month, followed by regression. Seizure at 2 months, His poor oral feeding was lifelong problem. Weak crying, spastic, choreoathetoid movement. Self mutilating behavior noted and diagnosed at age 3 years. No family history of consanguinity and neurological disorders. Method: Laboratory test, physical exam, imaging study and molecular. Clinical follow up Treat ment with allopurinol. Result: uric acid 10.5 mg/dL (N 3.5-7.9), APRT 151.1uM/ min/ml pro(25.7-101), HPRT 7.6 (N 233.5-701) and c.151C>T hemizygote (p,Arg51X). Abdominal sonogram showed staghorn calculi in both kidneys, brain MRI brain atrophy. Clinical follow up showed, seizure at 2 mo, developmental delay (head control and, rolling over at at 11mo, pointing body part at 2 yr 7 mo, eye hand coordination at 2 y 11mo,creeping at 3 y 7 mo, speaking words at 6 y 6 mo ),and developmental regression at 3 yr of age. Sleeping problem including insomnia and severe constipation. Self mutilating behavior (lip bite) started at 2.5 yr, neurologic sx including intermittent upward gaze accompanied by swallowing difficulty at 3 y 7 mo grand mal seizure at 4.5 yr and spastic extremity and trunchal hypotonia and choleoathetoid movement and ataxia at 6.5 yr. Scoliosis with severe spasticity at 9 yr 9 mo. Acute life threatening episode with irregular breathing at 9 yr and 9 mo, Emaciation and nephrolithiasis and recurrent pneumonia. Died suddenly at 10 yr 3 mo. Conclusion: life long feeding problem, chronic gut motility dysfunction, sleeping difficulty and progressing neurologic deterioration and nephrolithiasis despite normal serum uric acid maintence by allopurinol treatment.

• 대한유전성대사질환학회지
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• 제12권1호
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• pp.42-48
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• 2012

폼페병은 GAA 유전자의 돌연변이로 인해 acid ${\alpha}$-glucosidase (GAA) 효소가 완전 혹은 부분적으로 결핍되어 발생하는 드문 리소좀 축적질환의 하나이다. 전형적인 영아형 폼페병은 다기관을 침범하여 빠르게 진행하는 질환으로, 근긴장도 저하, 전신적인 근력 감퇴 및 비후성 심근병증이 주된 임상 양상이며 치료를 받지 않으면 보통 1-2세경에 사망에 이르게 된다. 재조합 GAA 효소 대체 요법은 이러한 영아형 폼페병 환자에서 병의 진행 경과를 늦추고 예후를 호전시키는데 효과적임이 이미 확인되었다. 본 연구에서는 단일 기관에서 경험한 비후성 심근병증으로 발현된 혈연 관계가 없는 세 명의 한국인 폼페병 환자의 임상 양상 및 유전학적 양상과 더불어 단기간의 효소 대체 요법 효과를 보고하고자 한다. 효소 대체 요법이 도입된 이래 영아형 폼페병의 자연 경과가 매우 호전된 바, 보다 조기에 진단하여 효소 대체 요법을 시작하는 것이 환자의 예후를 호전시키고 합병증을 최소화하는데 결정적일 것으로 생각된다.

• 대한소아치과학회지
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• 제29권2호
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• pp.237-242
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• 2002

Lowe 증후군 또는 안뇌신증후군(oculocerebrorenal syndrome)은 X-염색체와 관련된 유전성 질환으로 반성열성유전양상을 나타낸다. 선천성 백내장과 녹내장 등의 안 증상, 근긴장 저하 건반사감소 등의 근신경계 증상, 신장 기능이상이 가장 특징적인 임상 증상이며, 이외에도 정신 지체, 성장지연, 전두부 융기, 가늘고 성긴 모발, 돌출된 귀, 골질환 등이 발생할 수 있다. Lowe 증후군 환자는 정신지체로 인해 치과치료시 전신마취하에서의 처치가 요구되나, 대사성 산증, 악성고열의 발생위험과 사용약제에 의한 부작용 등이 위험요소로 작용할 수 있으므로, 필요한 경우 내과 또는 소아과 의료진이 참여된 협진체제 하에서 가능한 짧은 시간 진행되어야 한다. 이러한 치과적 처치의 어려움으로 Lowe 증후군 환자에서 치과질환의 예방이 좀더 강조되어야 하면, 이를 위해 보호자의 주위의 적극적 관리가 요구된다.

• Journal of Genetic Medicine
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• 제12권1호
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• pp.49-56
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• 2015

We herein report an analysis of a female baby with a de novo dup(10p)/del(10q) chromosomal aberration. A prenatal cytogenetic analysis was performed owing to abnormal ultrasound findings including a choroid plexus cyst, prominent cisterna magna, and a slightly medially displaced stomach. The fetal karyotype showed additional material attached to the terminal region of chromosome 10q. Parental karyotypes were both normal. At birth, the baby showed hypotonia, upslanting palpebral fissures, a nodular back mass, respiratory distress, neonatal jaundice and a suspicious polycystic kidney. We ascertained that the karyotype of the baby was 46,XX,der(10)($pter{\rightarrow}q26.3::p11.2{\rightarrow}pter$) by cytogenetic and molecular cytogenetic analyses including high resolution GTG-and RBG-banding, fluorescence in situ hybridization, comparative genomic hybridization, and short tandem repeat marker analyses. While almost all reported cases of 10p duplication originated from one of the parents with a pericentric inversion, our case is extraordinarily rare as the de novo dup(10p)/del(10q) presumably originated from a rearrangement at the premeiotic stage of the parental germ cell or from parental germline mosaicism.

• Clinical and Experimental Pediatrics
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• 제55권12호
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• pp.487-490
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• 2012

We report a case of isodicentric chromosome 15 (idic(15) chromosome), the presence of which resulted in uncontrolled seizures, including epileptic spasms, tonic seizures, and global developmental delay. A 10-month-old female infant was referred to our pediatric neurology clinic because of uncontrolled seizures and global developmental delay. She had generalized tonic-clonic seizures since 7 months of age. At referral, she could not control her head and presented with generalized hypotonia. Her brain magnetic resonance imaging scans and metabolic evaluation results were normal. Routine karyotyping indicated the presence of a supernumerary marker chromosome of unknown origin (47, XX +mar). An array-comparative genomic hybridization (CGH) analysis revealed amplification from 15q11.1 to 15q13.1. Subsequent fluorescence in situ hybridization analysis confirmed a idic(15) chromosome. Array-CGH analysis has the advantage in determining the unknown origin of a supernumerary marker chromosome, and could be a useful method for the genetic diagnosis of epilepsy syndromes associated with various chromosomal aberrations.

• 대한소아치과학회지
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• 제39권2호
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• pp.161-165
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• 2012

Lowe syndrome은 X-염색체 반성열성 유전 질환으로 1952년 Lowe 등에 의해 처음으로 보고되었다. 대부분 남성에게 발생하며, 주요 임상증상으로는 선천성 백내장 및 녹내장 등의 안구증상, 정신지체 및 근긴장저하 등의 근신경계 증상, 신장의 기능이상 등이 있고, 정신지체에 의한 행동조절 문제로 인해 전신마취를 시행할 경우 신장 기능 저하에 따른 대사성 산증과 악성 고열 발생의 위험성이 높아진다. Lowe syndrome으로 진단된 10세 2개월 된 남아가 치석이 많고, 칫솔질이 어렵다는 것을 주소로 전남대학교 치과병원 소아치과에 내원하였다. 임상 검사 시 전반적으로 심한 치석의 침착, 법랑질 형성 부전, 변연성 치은염, 영구치의 맹출 지연, 전반적인 치아 동요 등의 소견을 보였으며, 심한 정신지체로 인해 환자의 협조도가 부족하여 진정요법 하에 외래에서 치과치료를 시행하였다. 행동조절의 어려움과 전신마취시의 위험성, 대사장애 처치에 사용되는 각종 약물로 인한 치아착색과 치석형성의 용이함 때문에 Lowe syndrome 환아의 치과적 관리는 특히 예방에 중점을 두어야 한다.

• BMB Reports
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• 제35권2호
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• pp.213-219
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• 2002

Malonyl-CoA decarboxylase (E.C.4.1.1.9) catalyzes the conversion of malonyl-CoA to acetyl-CoA. Although the metabolic role of this enzyme has not been fully defined, it has been reported that its deficiency is associated with mild mental retardation, seizures, hypotonia, cadiomyopathy, developmental delay, vomiting, hypoglycemia, metabolic acidosis, and malonic aciduria. Here, we isolated a cDNA clone for malonyl CoA decarboxylase from a rat brain cDNA library, expressed it in E. coli, and characterized its biochemical properties. The full-length cDNA contained a single open-reading frame that encoded 491 amino acid residues with a calculated molecular weight of 54, 762 Da. Its deduced amino acid sequence revealed a 65.6% identity to that from the goose uropigial gland. The sequence of the first 38 amino acids represents a putative mitochondrial targeting sequence, and the last 3 amino acid sequences (SKL) represent peroxisomal targeting ones. The expression of malonyl CoA decarboxylase was observed over a wide range of tissues as a single transcript of 2.0 kb in size. The recombinant protein that was expressed in E. coli was used to characterize the biochemical properties, which showed a typical Michaelis-Menten substrate saturation pattern. The $K_m$ and $V_{max}$ were calculated to be $68\;{\mu}M$ and $42.6\;{\mu}mol/min/mg$, respectively.

• Journal of Genetic Medicine
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• 제9권1호
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• pp.42-46
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• 2012

Short-chain acyl-CoA dehydrogenase deficiency (SCADD; OMIM # 201470) is an autosomal recessive inborn error of mitochondrial fatty acid ${\beta}$-oxidation, presenting with a variety of clinical signs and symptoms. Developmental delay, hypertonia or hypotonia, ketotic hypoglycemia, and epilepsy are most frequently reported. In general, patients diagnosed through newborn screening have shown normal growth and development in contrast to those diagnosed as a result of clinically initiated evaluations. Here, the case of an asymptomatic Korean newborn with SCADD identified by tandem mass spectrometry is reported. The patient showed an elevated concentration of butyrylcarnitine detected on newborn screening. Urinary excretion of ethylmalonic acid was elevated by urine organic acid analysis. To confirm the diagnosis of SCADD, a direct sequencing analysis of 10 coding exons and the exon-intron boundaries of the ACADS gene were performed. Genetic analysis of ACADS showed the following novel compound heterozygous missense mutations: c.277C>A (p.Leu93Ile) on exon3 and c.682G>A (p.Glu288Lys) on exon6. These results will provide further evidence of mutational heterogeneity for SCADD.