Isolated carboxylase deficiency

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Classification according to ICD-10
E71.1 Other disorders of the metabolism of branched amino acids
ICD-10 online (WHO version 2019)

An isolated carboxylase deficiency is a very rare congenital , autosomal recessive inherited metabolic disorder of the leucine metabolism with muscle hypotonia and muscle atrophy .

The disease belongs to the multiple carboxylase deficiency group .

Synonyms are: 3-methylcrotonylglycinuria; MCC deficiency; MCCD; 3-methylcrotonyl-CoA carboxylase deficiency, more isolated; 3-MCC; 3MCC; BMCC deficiency

The first description comes from the year 1970 by the Norwegian doctors Lorentz Eldjarn, Egil Jellum, O. Stokke and colleagues.

distribution

The frequency is given as 1 - 9 in 100,000, inheritance is autosomal - recessive . It is one of the most common organoacidopathies .

root cause

Depending on the underlying mutation , the following types can be distinguished:

Clinical manifestations

Clinical criteria are:

  • variable clinical picture
  • Manifestation in the newborn with pronounced neurological changes up to first manifestation in the adult without neurological abnormalities
  • initially normal development, then episodes of metabolic imbalance with vomiting , opisthotonus , myoclonia , seizures up to coma and apnea
  • symptom-free intervals
  • progressive muscular atrophy and hypotonia in infancy

diagnosis

The diagnosis is usually made during neonatal screening using tandem mass spectrometry by detecting 3-methylcrotonylglycine and isovaleric acid in the urine and 3-hydroxyisovaleryl-carnitine in the blood serum , and sometimes ketoacidosis and / or hypoglycemia is found .

Differential diagnosis

The following are to be distinguished:

therapy

Treatment consists of reducing the amount of leucine in the diet and giving carnitine

literature

  • H. Fonseca, L. Azevedo, C. Serrano, C. Sousa, A. Marcão, L. Vilarinho: 3-Methylcrotonyl-CoA carboxylase deficiency: Mutational spectrum derived from comprehensive newborn screening. In: Genes. Volume 594, Number 2, December 2016, pp. 203-210, doi: 10.1016 / j.gene.2016.09.003 , PMID 27601257 .
  • R. Forsyth, CW Vockley, MJ Edick, CA Cameron, SJ Hiner, SA Berry, J. Vockley, GL Arnold: Outcomes of cases with 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency - Report from the Inborn Errors of Metabolism Information system. In: Molecular Genetics and Metabolism. Volume 118, number 1, May 2016, pp. 15-20, doi: 10.1016 / j.ymgme.2016.02.002 , PMID 27033733 , PMC 5540133 (free full text).
  • JA Thomsen, AM Lund, JH Olesen, M. Mohr, J. Rasmussen: Is L-Carnitine Supplementation Beneficial in 3-Methylcrotonyl-CoA Carboxylase Deficiency? In: JIMD Reports. Volume 21, 2015, pp. 79-88, doi : 10.1007 / 8904_2014_393 , PMID 25732994 , PMC 4470948 (free full text).
  • SC Grünert, M. Stucki u. a .: 3-methylcrotonyl-CoA carboxylase deficiency: Clinical, biochemical, enzymatic and molecular studies in 88 individuals. In: Orphanet Journal of Rare Diseases. 7, 2012, p. 31, doi: 10.1186 / 1750-1172-7-31

Individual evidence

  1. ↑ a b c 3-methylcrotonyl-CoA carboxylase deficiency, isolated. In: Orphanet (Rare Disease Database).
  2. ↑ 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 .
  3. ↑ L. Eldjarn, E. Jellum, O. Stokke, H. Pande, PE Waaler: Beta-hydroxyisovaleric aciduria and beta-methylcrotonylglycinuria: a new inborn error of metabolism. In: The Lancet . Volume 2, Number 7671, September 1970, pp. 521-522, PMID 4194964 .
  4. ↑ 3-Methylcrotonyl-CoA carboxylase 1 deficiency.  In: Online Mendelian Inheritance in Man . (English)
  5. ↑ 3-Methylcrotonyl-CoA carboxylase 2 deficiency.  In: Online Mendelian Inheritance in Man . (English)

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