• Title/Summary/Keyword: Metabolic myopathy

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A Novel PHKA1 Mutation in a Patient with Glycogen Storage Disease Type IXD (당원 축적병 9D (GSD9D) 환자의 신규 PHKA1 돌연변이)

  • Kim, Hye Jin;Nam, Soo Hyun;Kim, Sang Beom;Chung, Ki Wha;Choi, Byung-Ok
    • Journal of Life Science
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    • v.30 no.8
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    • pp.672-679
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    • 2020
  • Distal myopathy is a clinically and genetically heterogeneous group of degenerative diseases of the distal muscle. Glycogen storage disease type IXD (GSD9D) is a metabolic distal myopathy characterized by muscle deficiency of phosphorylase kinase, a key regulatory enzyme in glycogen metabolism. Affected individuals may develop muscle weakness, degeneration, and cramps, as well as abnormal muscle pain and stiffness after exercise. It has been reported that mutations in the PHKA1 gene which encodes the alpha subunit of muscle phosphorylase kinase cause GSD9D. In this study, we examined a Korean GSD9D family with a c.3314T>C (p.I1105T) mutation in the PHKA1 gene. This mutation has not been previously reported in any mutation database nor was it found in 500 healthy controls. The mutation region is well conserved in various other species, and in silico analysis predicts that it is likely to be pathogenic. To date, only seven mutations in the PHKA1 gene have been documented, and this is the first report of Korean GSD9D patients. This study also describes and compares the clinical symptoms and pathological conditions of previously reported cases and these Korean patients. We believe that our findings will be useful for the molecular diagnosis of GSD9D.

A Case of Late-onset Episodic Myopathic Form with Intermittent Rhabdomyolysis of Very-long-chain acyl-coenzyme A Dehydrogenase (VLCAD) Deficiency Diagnosed by Multigene Panel Sequencing (유전자패널 시퀀싱으로 진단된 성인형 very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) 결핍증 증례)

  • Sohn, Young Bae;Ahn, Sunhyun;Jang, Ja-Hyun;Lee, Sae-Mi
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.19 no.1
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    • pp.20-25
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    • 2019
  • Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (OMIM#201475) is an autosomal recessively inherited metabolic disorder of mitochondrial long-chain fatty acid oxidation. The clinical features of VLCAD deficiency is classified by three clinical forms according to the severity. Here, we report a case of later-onset episodic myopathic form of VLCAD deficiency whose diagnosis was confirmed by plasma acylcarnitine analysis and" multigene panel multigene panel sequencing. A 34-year old female patient visited genetics clinic for genetic evaluation for history of recurrent myopathy with intermittent rhabdomyolysis. She suffered first episode of rhabdomyolysis with acute renal failure requiring hemodialysis at twelve years old. After then, she suffered several times of recurrent rhabdomyolysis provoked by prolonged exercise or fasting. Physical and neurologic exam was normal. Serum AST/ALT and creatinine kinase (CK) levels were mildly elevated. However, according to her previous medical records, her AST/ALT, CK were highly elevated when she had rhabdomyolysis. In suspicion of fatty acid oxidation disorder, multigene panel sequencing and plasma acylcarnitine analysis were performed in non-fasting, asymptomatic condition for the differential diagnosis. Plasma acylcarnitine analysis revealed elevated levels of C14:1 ($1.453{\mu}mol/L$; reference, 0.044-0.285), and C14:2 ($0.323{\mu}mol/L$; 0.032-0.301) and upper normal level of C14 ($0.841{\mu}mol/L$; 0.065 -0.920). Two heterozygous mutation in ACADVL were detected by multigene panel sequencing and confirmed by Sanger sequencing: c.[1202G>A(;) 1349G>A] (p.[(Ser 401Asn)(;)(Arg450His)]). Diagnosis of VLCAD deficiency was confirmed and frequent meal with low-fat diet was educated for preventing acute metabolic derangement. Fatty acid oxidation disorders have diagnostic challenges due to their intermittent clinical and laboratorial presentations, especially in milder late-onset forms. We suggest that multigene panel sequencing could be a useful diagnostic tool for the genetically and clinically heterogeneous fatty acid oxidation disorders.

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Clinical Observation on Hyperthyroidism (갑상선기능항진증(甲狀腺機能亢進症)의 임상적(臨床的) 관찰(觀察))

  • Lee, Kyu-Bo;Kang, Bann;Song, Suk-Ho;Park, Hi-Myung;Whang, Kee-Suk
    • The Korean Journal of Nuclear Medicine
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    • v.3 no.2
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    • pp.39-47
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    • 1969
  • A clinical analysis was made on 161 cases of hyperthyroidism seen at the Radioisotope Laboratory of Kyungpook National University Hospital. This series consisted of 144 cases of diffuse goiter and 17 cases of nodular goiter. 1) Hyperthyroidism was most prevalent in the 4th decade and male to female ratio was 1:4.6. 2) Cardinal symptoms in the order of frequency were weakness, easy fatigability, palpitation, weight loss, nervousness, perspiration, heat intolerance, increased appetite, insomnia and dysmenorrhea. 3) Major physical findings in the order of frequency were goiter, fine tremor, tachycardia, wide pulse pressure, emaciation, warm moist skin, exophthalmos, systolic hypertension and atrial fibrillation. 4) The complications were ophthalmopathy (34.2%), thyrotoxic heart disease (5.6%), thyroid crisis (1 case), pretibial myxedema (1 case) and thyrotoxic myopathy (1 case). 5) Mean values of the six hour and twenty-four hour $^{131}I$ uptakes by the thyroid glands were 67.5% and 71.6%, respectively, in diffuse goiter and 64.5% and 65.0%, respectively, in nodular goiter. 6) Mean values of twenty-four hour $PB^{131}I$ conversion ratio were 76.3% in diffuse goiter and 70.2% in nodular goiter and those of the basal metabolic rate was +51% in the former and +41% in the latter. Mean serum cholesterol level was 152mg% in diffuse goiter and that in nodular goiter was 175mg%. 7) Among the 134 cases treated with $^{131}I$, 66 cases (49.3%) were successful1y controlled with single dose and in the majority of the cases the initial therapeutic dose required was $4.1{\sim}5.0mC$ in diffuse goiter and $5.1{\sim}6.0mC$ in nodular goiter. 8) With $^{131}I$ treatment the symptoms improved in the following order: heat intolerance, emaciation, nervousness, insomnia, easy fatigability, weakness, fine tremor, goiter, perspiration, exertional dyspnea and palpitation. And in a few cases improvement of even exophthalmos was seen. 9) Following $^{131}I$ treatment myxedema occurred in 4 cases (3%) and reccurrence in 9 cases (6.8%).

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AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III

  • Ko, Jung-Min;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.4 no.1
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    • pp.72-79
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    • 2007
  • Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.

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