pyruvate kinase deficiency

ピルビン酸キナーゼ欠乏症

WordNet

1. an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
2. the basic unit of money in Papua New Guinea

PrepTutorEJDIC

1. 〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/30 08:55:33」(JST)

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Pyruvate kinase deficiency
Phosphoenolpyruvate
Classification and external resources
ICD-10	D55.2
ICD-9	282.3
OMIM	266200
DiseasesDB	11090
MedlinePlus	001197
eMedicine	med/1980
Patient UK	Pyruvate kinase deficiency

Distribution of red blood cell abnormalities worldwide

Pyruvate kinase deficiency, also called erythrocyte pyruvate kinase deficiency, is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells and causes them to deform into echinocytes ("burr cells") on peripheral blood smears.

Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive.

Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.

Causes

A variety of mutations can lead to lowered production, activity, or stability of pyruvate kinase, an enzyme essential to glycolysis. A total lack of this enzyme's activity will be lethal[citation needed].

Pathophysiology

Erythrocytes manufacture ATP through glycolysis. A deficiency in pyruvate kinase, the enzyme that potentiates the last step of glycolysis (phosphoenolpyruvate converted to pyruvate), results in red blood cells (RBCs) with decreased energy.

Because red blood cells cannot synthesize ATP, cellular death occurs. cell death is by shrinking. this is called a 'dehydration at cellular level'. Due to the unavailability of adequate ATP,all active processes in the red blood cell comes to a halt. Sodium potassium ATPase pumps are the first to stop. Since the cell membrane is more permeable to potassium than sodium, potassium leaks out. Inter cellular fluid becomes hypotonic. Water moves down it's concentration gradient out of the cells. Finally cells shrink and die. The mechanism of how distorted red blood cells are destroyed in the spleen is not understood well. Partial splenectomies are sometimes performed as a treatment for anemias due to an underlying inability for RBC deformation (hereditary spherocytosis and pyruvate kinase deficiency). This is usually reserved for severe transfusion-dependent anemias as removal of the spleen confers a susceptibility to encapsulated organisms.

The buildup of reaction intermediates can also increase the level of 2,3-bisphosphoglycerate (2,3 BPG) in the cells and affect tissue oxygenation. This will cause a "right shift" in the hemoglobin oxygen saturation curve, implying a decreased oxygen affinity for the hemoglobin and earlier oxygen unloading than under normal conditions. As a result, individuals with pyruvate kinase deficiency may have a greater capacity for physical activity than others with similarly low hemoglobin levels.

Symptoms

The lysis of the RBCs leads to hemolytic anemia in the newborn and may cause jaundice from increased bilirubin.

Treatment

Most affected individuals do not require treatment. Individuals who are most severely affected may die in utero of anemia or may require blood transfusions or splenectomy, but most of the symptomatology is limited to early life and times of physiologic stress or infection.

Treatment can include a blood transfusion or removal of the spleen. Treatment is usually effective in reducing the severity of the symptoms.

See also

• List of hematologic conditions

References

UpToDate Contents

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• 1. ピルビン酸キナーゼ欠損症 pyruvate kinase deficiency
• 2. 小児における溶血性貧血の概要 overview of hemolytic anemias in children
• 3. 新生児における同種免疫性溶血性疾患の出生後診断およびマネージメント postnatal diagnosis and management of alloimmune hemolytic disease of the newborn
• 4. 成人における溶血性貧血の診断へのアプローチ approach to the diagnosis of hemolytic anemia in the adult
• 5. 棘状細胞（棘状赤血球および有棘赤血球）と標的細胞 spiculated cells echinocytes and acanthocytes and target cells

English Journal

• Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis.

• van Zwieten R1, van Oirschot BA, Veldthuis M, Dobbe JG, Streekstra GJ, van Solinge WW, Schutgens RE, van Wijk R.
• American journal of hematology.Am J Hematol.2014 Nov 12. doi: 10.1002/ajh.23899. [Epub ahead of print]
• In a family with mild dominant spherocytosis, affected members showed partial band 3 deficiency. The index patient showed more severe clinical symptoms than his relatives, and his red blood cells displayed concomitant low pyruvate kinase activity. We investigated the contribution of partial PK defic
• PMID 25388786

• Causes of hemolysis in neonates with extreme hyperbilirubinemia.

• Christensen RD1, Nussenzveig RH2, Yaish HM3, Henry E1, Eggert LD1, Agarwal AM2.
• Journal of perinatology : official journal of the California Perinatal Association.J Perinatol.2014 Aug;34(8):616-9. doi: 10.1038/jp.2014.68. Epub 2014 Apr 24.
• OBJECTIVE: We instituted a quality improvement process to enhance our capacity to diagnose genetic hemolytic conditions in neonates with extreme hyperbilirubinemia.STUDY DESIGN: During a 1-year period, whenever the total serum bilirubin (TSB) was >25 mg dl(-1) a special evaluation was performed.
• PMID 24762414

• Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney.

• Haija MA1, Qian YW, Muthukumar A.
• Pediatric blood & cancer.Pediatr Blood Cancer.2014 Aug;61(8):1463-5. doi: 10.1002/pbc.24953. Epub 2014 Jan 30.
• Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical
• PMID 24481986

Japanese Journal

• 赤血球ピルビン酸キナーゼ(PK) (広範囲 血液・尿化学検査 免疫学的検査(第7版・2)その数値をどう読むか) -- (血球化学検査)

• 菅野 仁
• 日本臨床 68(-) (970), 885-889, 2010-01
• NAID 40016932983

• Congenital insensitivity to pain with anhidrosis (CIPA) : Novel mutations of the TRKA (NTRK 1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency

• INDO Y.
• Hum Mutat 18, 308-318, 2001
• NAID 30004130039

• 造血幹細胞に対する遺伝子治療研究の現状 : 赤血球酵素異常症の根治療法開発に向けての基礎研究

• 菅野 仁
• 日大醫學雜誌 59(4), 139-145, 2000-04-01
• NAID 10009456474

Related Links

• Pyruvate Kinase Deficiency | Understanding and living with PKD

If you or a family member have been diagnosed with Pyruvate Kinase Deficiency, you probably have many questions running through your head. What kind of disease is it? Will I or my family member be able to live a normal life? What ...

• pyruvate kinase deficiency - definition of pyruvate kinase ...

Pyruvate Kinase Deficiency Definition Pyruvate kinase deficiency (PKD) is part of a group of disorders called hereditary nonspherocytic hemolytic anemias. Hereditary nonspherocytic anemias are rare genetic conditions that affect the ...

Related Pictures

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★リンクテーブル★

リンク元	「溶血性貧血」「ピルビン酸キナーゼ欠乏症」
関連記事	「deficiency」「kinase」「pyruvate」「pyruvate kinase」

「溶血性貧血」

　　[★]

英

hemolytic anemia

同

溶血性黄疸 hemolytic jaundice

関

貧血

溶血の種類	機序	脾腫	ヘモグロビン尿 ヘモジデリン尿	疾患
血管外溶血	Mφで貪食される	＋	－	球状赤血球症 HS 自己免疫性溶血性貧血 AIHA (温式) ↑冷式より多い
血管内溶血	血管内で溶血	－	＋	自己免疫性溶血性貧血 AIHA (冷式) 発作性夜間ヘモグロビン尿症 PNH G6PD欠損症 赤血球破砕症候群 不適合輸血

概念

• 赤血球寿命が種々の原因により短縮することに伴う貧血の総称。

病因

• 赤血球が何らかの原因により破壊され、骨髄の代償能力を超えて赤血球が減少することにより貧血を呈する。　→　溶血が存在するが貧血ではない状態がある。
• 溶血の原因

• 先天性疾患

• 遺伝性球状赤血球症(70%)
• 遺伝性楕円赤血球症
• ヘモグロビン異常症、酵素欠乏症

• 後天性疾患

• 自己抗体による溶血

• 自己免疫性溶血性貧血(温式抗体、冷式抗体)、発作性夜間ヘモグロビン尿症、赤血球破砕症候群

HIM.653

赤血球内の素因

• 1. ヘモグロビンの異常
• 2. 膜-細胞骨格複合体の異常

• 遺伝性球状赤血球症(溶血性貧血のなかで一般的なもの。赤血球の細胞膜蛋白・細胞骨格の異常により球状となり脾臓で捕捉され溶血する)、hereditary elliptocytosis HE
• stomatocytosis

• 3. 代謝経路

• 解糖系の異常：pyruvate kinase deficiency
• 還元系の異常：glucose 6-phosphate dehydrogenase deficiency
• 核酸異化異常：pyrimidine 5'-nucleotidase deficiency

赤血球外の素因

• 先天性

• 家族性溶血尿毒症 familial hemolytic uremic syndrome

• 後天性

• 赤血球の機械的損傷
• 毒物・薬物
• 感染
• 自己免疫性溶血性貧血 AIHA

• 発作性寒冷血色素尿症 paroxysmal cold hemoglobinuria PCH
• 寒冷凝集素症 cold agglutinin disease CAD

• 発作性夜間血色素尿症 PNH

症状

• 貧血、無胆汁色素尿性または溶血性黄疸、脾腫

参考

• [charged]Extrinsic nonimmune hemolytic anemia due to mechanical damage: Fragmentation hemolysis and hypersplenism - uptodate

http://www.uptodate.com/contents/extrinsic-nonimmune-hemolytic-anemia-due-to-mechanical-damage-fragmentation-hemolysis-and-hypersplenism?source=search_result&selectedTitle=2%7E150

「ピルビン酸キナーゼ欠乏症」

　　[★]

英

pyruvate kinase deficiency PK deficiency, PKD, deficiency of pyruvate kinase, deficiency of PK

同

ピルビン酸キナーゼ欠損症

関

ピルビン酸キナーゼ

• first aid step1 2006 p.89

遺伝

• 常染色体劣性遺伝

病態生理

• ピルビン酸キナーゼ pyruvate kinaseの著しい活性低下により赤血球内のATP産生が阻害される　→　ATP欠乏により赤血球の細胞膜よりカリウムが流出して溶血を来す。、

• 赤血球：ATP、ピルビン酸、NADの減少。2,3-DPGの増加

症状

• 黄疸、溶血性貧血

USMLE

• Q book p.140 39

「deficiency」

　　[★]

• n.

• 不足、欠乏、欠失、欠如、欠損、不十分。栄養不足、栄養素欠乏、欠乏症。(遺伝子)(染色体内の)遺伝子欠失
• 欠けているもの、不足している物。不足分。不完全なもの、欠点のあるもの

関

absence, agenesis, dearth, defect, defective, deficient, deficit, delete, deletion, deletional, depletion, deprivation, deprive, lack, miss, missing, morphological defect, paucity, scarce, scarcity, starve

　

「kinase」

　　[★] キナーゼ カイネース リン酸化酵素 phosphoenzyme phosphotransferase 　

「pyruvate」

　　[★] ピルビン酸 pyruvic acid

「pyruvate kinase」

　　[★] ピルビン酸キナーゼ