Pyruvate carboxylase deficiency

Classification according to ICD-10
E74.4	Disorders of pyruvate metabolism and gluconeogenesis
ICD-10 online (WHO version 2019)

The pyruvate carboxylase deficiency (PC) deficiency is a very rare congenital Neurometabolic disease with the main characteristics occurring in childhood metabolic acidosis , failure to thrive , developmental delay and seizures .

Synonyms are: pyruvate carboxylase defect; congenital lactic acidosis; Ataxia with lactic acidosis; Ataxia with lactic acidosis type 2; Leigh syndrome due to pyruvate carboxylase deficiency; Necrotizing encephalopathy due to pyruvate carboxylase deficiency

The first description comes from the year 1969 by the Japanese pediatricians Keiya Tada, Toshio Yoshida, Tasuke Konno and colleagues.

Classification

There are three forms:

Type A, infantile form , synonym: pyruvate carboxylase deficiency type A , onset in infancy with a severe course
Type B, neonatal form , synonym: pyruvate carboxylase deficiency type B , death in early childhood
Type C, benign form , favorable course, recurring metabolic acidosis

distribution

The frequency is given as 1 in 250,000, inheritance is autosomal - recessive .

root cause

The disease is based on mutations in the pyruvate carboxylase gene PC - gene on chromosome 11, locus q13.2.

Clinical manifestations

Clinical criteria are:

Manifestation shortly after birth (type B), a little later (type A)
metabolic acidosis, severe or intermittent (type C)
Seizure , hypertension
Encephalopathy

diagnosis

The blood serum contains significantly increased lactates as well as pyruvates and alanine , as well as changed plasma levels of glucose and ammonia .

The diagnosis can be confirmed by human genetic detection of the mutation or by measuring the pyruvate carboxylase activity in fibroblasts .

Differential diagnosis

The following are to be distinguished:

forecast

The life expectancy is unfavorable for type A and type B, the victims usually die in Kleinkindes- or childhood. People with type C usually have a normal life expectancy.

literature

C. Egloff, A. Eldin de Pecoulas, C. Mechler, M. Tassin, V. Mairovitz, F. Corrizi, C. Dussaux, A. Boutron, I. Simon, A. Guet, J. Sibiude, L. Mandelbrot, O. Picone: Prenatal sonographic description of fetuses affected by pyruvate dehydrogenase or pyruvate carboxylase deficiency. In: Prenatal diagnosis. [Electronic publication before going to press] May 2018, doi: 10.1002 / pd.5282 , PMID 29752808 .

F. Habarou, A. Brassier, M. Rio, D. Chrétien, S. Monnot, V. Barbier, R. Barouki, JP Bonnefont, N. Boddaert, B. Chadefaux-Vekemans, L. Le Moyec, J. Bastin, C. Ottolenghi, P. de Lonlay: Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis. In: Molecular genetics and metabolism reports. Volume 2, March 2015, pp. 25–31, doi: 10.1016 / j.ymgmr.2014.11.001 , PMID 28649521 , PMC 5471145 (free full text).

E. Ostergaard, M. Duno, LB Møller, HS Kalkanoglu-Sivri, A. Dursun, D. Aliefendioglu, H. Leth, M. Dahl, E. Christensen, F. Wibrand: Novel Mutations in the PC Gene in Patients with Type B Pyruvate Carboxylase Deficiency. In: JIMD Reports. Volume 9, 2013, pp. 1–5, doi : 10.1007 / 8904_2012_173 , PMID 23430542 , PMC 3565670 (free full text).

Pyruvate Carboxylase Deficiency . In: Gene Reviews . PMID 20301764

Web links

Individual evidence

↑ ^a ^b ^c 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 .
↑ ^a ^b ^c ^d ^e ^f Pyruvate carboxylase deficiency. In: Orphanet (Rare Disease Database).
↑ ^a ^b emedicine
↑ K. Tada, T. Yoshida, T. Konno, Y. Wada, Y. Yokoyama: Hyperalaninemia with pyruvicemia (preliminary report). In: The Tohoku journal of experimental medicine. Volume 97, Number 1, January 1969, pp. 99-100, PMID 5771860 .
↑ Pyruvate carboxylase deficiency, infantile form. In: Orphanet (Rare Disease Database).
↑ Pyruvate carboxylase deficiency, severe neonatal type. In: Orphanet (Rare Disease Database).
↑ Pyruvate carboxylase deficiency, benign type. In: Orphanet (Rare Disease Database).
↑ Pyruvate carboxylase deficiency. In: Online Mendelian Inheritance in Man . (English)
↑ Holocarboxylase synthetase deficiency. In: Orphanet (Rare Disease Database).
↑ Multiple carboxylase deficiency. In: Orphanet (Rare Disease Database).

[Leiber-1] 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 .

[Orpha-2] ↑ ^a ^b ^c ^d ^e ^f Pyruvate carboxylase deficiency. In: Orphanet (Rare Disease Database).

[emed-3] ↑ ^a ^b emedicine

[4] K. Tada, T. Yoshida, T. Konno, Y. Wada, Y. Yokoyama: Hyperalaninemia with pyruvicemia (preliminary report). In: The Tohoku journal of experimental medicine. Volume 97, Number 1, January 1969, pp. 99-100, PMID 5771860 .

[5] Pyruvate carboxylase deficiency, infantile form. In: Orphanet (Rare Disease Database).

[6] Pyruvate carboxylase deficiency, severe neonatal type. In: Orphanet (Rare Disease Database).

[7] Pyruvate carboxylase deficiency, benign type. In: Orphanet (Rare Disease Database).

[8] Pyruvate carboxylase deficiency. In: Online Mendelian Inheritance in Man . (English)

[9] Holocarboxylase synthetase deficiency. In: Orphanet (Rare Disease Database).

[10] Multiple carboxylase deficiency. In: Orphanet (Rare Disease Database).