Holocarboxylase synthetase deficiency
| Classification according to ICD-10 | |
|---|---|
| E53.8 | Deficiency of other specified vitamins of the vitamin B complex deficiency |
| ICD-10 online (WHO version 2019) | |
A holocarboxylase synthetase deficiency (HCS) is a very rare congenital , autosomal recessive inherited metabolic disorder of biotin metabolism with early life-threatening disease onset with vomiting , tachypnea , seizures , irritability and lethargy to coma .
The holocarboxylase synthetase deficiency belongs to the multiple carboxylase deficiency .
Synonyms are: Holocarboxylase synthase deficiency; Multiple carboxylase deficiency, early onset; Multiple carboxylase deficiency, neonatal; Carboxylase defect, multiple; Carboxylase defect, biotin-sensitive, multiple; English holocarboxylase synthetase deficiency
The first description comes from 1971 by the British doctor D. Gompertz and coworkers, another description comes from 1979 by the US human geneticist Jess Thoene and coworkers.
distribution
The frequency is not known; it is given as less than 1 in 200,000 live births. Inheritance is autosomal - recessive .
root cause
The disease are mutations in HLCS - gene on chromosome 21 locus q22.13 based on which the synthetase Holocarboxylase coded. This enzyme is required by biotinidase .
Clinical manifestations
Clinical criteria are:
- Manifestation immediately up to weeks after birth
- Failure to thrive , vomiting , lethargy , hypotonia
- exfoliative dermatitis
If left untreated, seizures, cerebral edema and even coma occur.
diagnosis
The diagnosis is based on clinical and laboratory tests with ketoacidosis , lactic acidosis and hyperammonaemia . The diagnosis can be confirmed by detection of the reduced enzyme activity in leukocytes or fibroblasts or by human genetics . A prenatal diagnosis is possible.
Differential diagnosis
The following are to be distinguished:
- Biotinidase deficiency
- Isolated carboxylase deficiency , synonyms: 3-methylcrotonylglycinuria; MCC deficiency; MCCD; 3-methylcrotonyl-CoA carboxylase deficiency, isolated ,
therapy
Treatment consists of replacement therapy with free biotin .
forecast
If left untreated, mortality is high, and early diagnosis helps prevent damage from metabolic crisis .
literature
- J. Thoene, H. Baker, M. Yoshino, L. Sweetman: Biotin-responsive carboxylase deficiency associated with subnormal plasma and urinary biotin. In: The New England Journal of Medicine . Volume 304, Number 14, April 1981, pp. 817-820, doi: 10.1056 / NEJM198104023041404 , PMID 6782477 .
Individual evidence
- ↑ 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 g h Holocarboxylase synthetase deficiency. In: Orphanet (Rare Disease Database).
- ↑ ER Baumgartner, T. Suormala: Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. In: Int. J. Vitam. Nutr. Res. Volume 67, No. 5, 1997, pp. 377-384 PMID 9350481 .
- ↑ D. Gompertz, GH Draffan, JL Watts, D. Hull: Biotin-responsive beta-methylcrotonylglycinuria. In: The Lancet . Volume 2, Number 7714, July 1971, pp. 22-24, PMID 4103667 .
- ↑ J. Thoene, L. Sweetman, M. Yoshino: Biotin-responsive multiple carboxylase deficiency. (Abstract) In: American Journal of Human Genetics . Vol. 31, S-64A, 1979.
- ↑ Holocarboxylase synthetase deficiency. In: Online Mendelian Inheritance in Man . (English)
- ↑ 3-methylcrotonyl-CoA carboxylase deficiency, more isolated. In: Orphanet (Rare Disease Database).
