Pyruvate dehydrogenase deficiency

from Wikipedia, the free encyclopedia
Classification according to ICD-10
E74.4 Disorders of pyruvate metabolism and gluconeogenesis
ICD-10 online (WHO version 2019)

The pyruvate dehydrogenase deficiency is a very rare congenital neuro-metabolic disease with disturbances in pyruvate dehydrogenase complex .

Depending on the mitochondrial enzyme affected ( pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2) or dihydrolipoyl dehydrogenase (E3)), the clinical picture ranges from severe lactic acidosis in the newborn to neurological diseases with a later onset.

Synonyms are: congenital lactic acidosis, pyruvate dehydrogenase complex deficiency, English pyruvate dehydrogenase (complex) deficiency

The first description comes from 1970 by the Americans John P. Blass, Joel Avigan and B. William Uhlendorf .

distribution

The frequency is given as less than 1 in 1,000,000, the inheritance is partly autosomal - recessive , partly X-linked dominant .

Classification

The following classification according to the subunits of the PDH complex is currently used:

  • PDHD by E1-alpha deficiency (PDHA1) , mutations in PDHA1 - gene on the X chromosome locus p21.12, X-linked dominant
  • PDHD due to E1 beta deficiency , mutations in the PDHB gene on chromosome 3 locus p14.3, autosomal recessive
  • PDHD due to E2 deficiency (PDHB) , mutations in the DLAT gene on chromosome 11 locus q23.1, autosomal recessive
  • PDHD due to E3 deficiency , synonyms: dihydro-lipoamide dehydrogenase deficiency; Maple syrup disease, E3 deficient; DLD deficiency , mutations in the DLD gene on chromosome 7 locus q31.1, autosomal recessive
  • PDHD due to deficiency of the E3-binding protein , synonyms: 2-oxo-glutarate complex deficiency; Diaphorase deficiency; Dihydrolipoamide dehydrogenase binding protein deficiency of the pyruvate dehydrogenase complex; Dihydrolipoyl dehydrogenase deficiency; GCSL deficiency; Lipoamide dehydrogenase deficiency; Deficiency of the E3 subunit of the pyruvate dehydrogenase complex; Pyruvate Dehydrogenase Protein X Component Deficiency; Branched-chain alpha-keto acid dehydrogenase complex deficiency , mutations in the PDX1 gene on chromosome 11, locus p13, autosomal recessive
  • PDH phosphatase deficiency (PDHPD) , mutations in the PDP1 gene on chromosome 8 locus q22.1, autosomal recessive

Clinical manifestations

Clinical criteria are:

The clinical picture of Leigh syndrome is often present .

diagnosis

A combination of early onset of neurological abnormalities, lactic acidosis and abnormalities of the brain should lead to suspicion of pyruvate dehydrogenase deficiency. The lactate concentration in the cerebrospinal fluid is often significantly higher than that in the blood plasma . The diagnosis is confirmed by demonstrating the impaired enzyme function.

Differential diagnosis

There are other causes of lactic acidosis such as pyruvate carboxylase deficiency , defects in gluconeogenesis and other mitochondrial diseases, as well as Leigh's syndrome .

literature

  • GK Brown, LJ Otero, M. LeGris, RM Brown: Pyruvate dehydrogenase deficiency. In: Journal of medical genetics. Vol. 31, No. 11, November 1994, pp. 875-879, PMID 7853374 , PMC 1016663 (free full text) (review).
  • E. Dworzak, H. Grunicke, H. Berger, E. Jarosch, H. Haas, I. Höpfel: Pyruvate dehydrogenase deficiency in a child with persistent lactic acidosis. In: Journal of clinical chemistry and clinical biochemistry. Journal of Clinical Chemistry and Clinical Biochemistry. Vol. 23, No. 6, June 1985, pp. 323-329, PMID 3926941 .

Individual evidence

  1. ↑ a b Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
  2. ↑ a b c d e f Pyruvate dehydrogenase deficiency. In: Orphanet (Rare Disease Database).
  3. ↑ JP Blass, J. Avigan, BW Uhlendorf: A defect in pyruvate decarboxylase in a child with at intermittent movement disorder. In: The Journal of clinical investigation. Vol. 49, No. 3, March 1970, pp. 423-432, doi: 10.1172 / JCI106251 , PMID 4313434 , PMC 322489 (free full text).
  4. ↑ Pyruvate dehydrogenase E1-alpha deficiency.  In: Online Mendelian Inheritance in Man . (English)
  5. ↑ Pyruvate dehydrogenase E1-alpha deficiency. In: Orphanet (Rare Disease Database).
  6. ↑ Pyruvate dehydrogenase E1-beta deficiency. In: Orphanet (Rare Disease Database).
  7. ↑ Pyruvate dehydrogenase E1-beta deficiency.  In: Online Mendelian Inheritance in Man . (English)
  8. ↑ Pyruvate dehydrogenase E2 deficiency. In: Orphanet (Rare Disease Database).
  9. ↑ Pyruvate dehydrogenase E2 deficiency.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ Pyruvate dehydrogenase E3 deficiency. In: Orphanet (Rare Disease Database).
  11. ↑ Dihydrolipoamide dehydrogenase deficiency.  In: Online Mendelian Inheritance in Man . (English)
  12. ↑ Pyruvate dehydrogenase protein X component deficiency. In: Orphanet (Rare Disease Database).
  13. ↑ Lacticacidemia due to PDX1 deficiency.  In: Online Mendelian Inheritance in Man . (English)
  14. ↑ Pyruvate dehydrogenase phosphatase deficiency.  In: Online Mendelian Inheritance in Man . (English)

Web links