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FAH gene novel mutation을 가진 만성형 Hereditary tyrosinemia 1형

Chronic Hereditary Tyrosinemia Type I with Novel Mutation in FAH Gene

대한유전성대사질환학회지 2020년 20권 2호 p.55 ~ 62
Yang Sung-Min, 최효원, 강윤구, 이진성, Namgoong Mee-Kyung,
소속 상세정보
 ( Yang Sung-Min ) - Yonsei University Wonju College of Medicine Wonju Severance Christian Hospital Department of Pediatrics
최효원 ( Choi Hyo-Won ) - Yonsei University Wonju College of Medicine Wonju Severance Christian Hospital Department of Pediatrics
강윤구 ( Kang Yun-Koo ) - Yonsei University Wonju College of Medicine Wonju Severance Christian Hospital Department of Pediatrics
이진성 ( Lee Jin-Sung ) - Yonsei University College of Medicine Severance Children’s Hospital Department of Pediatrics
 ( Namgoong Mee-Kyung ) - Yonsei University Wonju College of Medicine Wonju Severance Christian Hospital Department of Pediatrics

Abstract


A 22-month-old girl who had taken iron supplements due to iron deficiency anemia, presented bloody mucoid stool for one month. She had a bruise at the right periorbital area due to minor trauma and hepatosplenomegaly. Laboratory studies showed anemia, thrombocytopenia, elevated alkaline phosphatase (ALP), hypophosphatemia, decreased haptoglobin, hypocomplementemia, negative direct/indirect Coomb's test, normal vitamin D3 level and high PTHi. Wrist x-ray showed no signs of rickets. The abdominal ultrasound showed only accessory spleen. Tandem mass spectrometry was normal. During follow up, bloody stool regressed after seven days of withdrawal of iron supplement and cow milk, and the total CO2 level had been within 15-20 mEq/L with normal anion gap. NGS (next generation sequencing) panel test for evaluation of renal tubular acidosis showed negative results. After low dose steroid and vitamin D supplements under the impression of hypocomplementemic vasculitis, thrombocytopenia, C3/C4, decreased haptoglobin, and elevated ALP level became normal. At 57 months of age, laboratory findings showed elevated liver enzyme, ALP and gamma-glutamyl transferase again. And liver cirrhosis with splenomegaly and diffuse renal disease were reported with abdomen CT scan. Liver biopsy reported macro- and micronodular cirrhosis. Urine organic acid profile showed elevated succinylacetone level. Whole exome sequencing revealed novel compound heterozygous mutations (NM_00137.2:c.107T>C, NM_00137, 2:c.614T>C) in FAH gene and confirmed by Sanger sequencing. Consequently, the patient was diagnosed as chronic hereditary tyrosinemia type I. She started low phenylalanine/tyrosine diet and nitisinone treatment. Our case had presented symptoms very slowly, which is the first case of chronic tyrosinemia type I in South Korea.

키워드

Hereditary tyrosinemia type 1; Chronic tyrosinemia; Metabolic disorder; Tandem mass spectrometry

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