HSD10 deficiency

Classification according to ICD-10
E72.8	Other specified disorders of amino acid metabolism
ICD-10 online (WHO version 2019)

The HSD10 deficiency (or disease) is a very rare congenital to the mitochondrial scoring Neurodegenerative disease with the main features of X-linked inheritance, manifestation during the neonatal , children or adolescents. The extent and time of the onset of the disease are very variable.

Synonyms are: 2-methyl-3-hydroxybutyraziduria; 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency; HSD10 disease; MHBD deficiency; English HSD10 Mitochondrial Disease; HSD10MD; HSD17B10 Deficiency; 17beta-hydroxysteroid-dehydrogenase Type 10 Deficiency

The first description comes from the year 2000 by a working group from Heidelberg , Amsterdam and Sankt Augustin .

distribution

The frequency is not known, the inheritance is X-linked dominant , the male gender is mainly affected.

root cause

Of the disease are - at least partly - mutations in HSD17B10 - gene on the X chromosome locus p11.22 based coding for the enzyme encoded HSD10 (17beta-hydroxysteroid dehydrogenase Type 10).

This enzyme is found in the mitochondria and is involved in the breakdown of isoleucine , branched-chain fatty acids , the production of androgens , estrogens and neurosteroids .

Classification

The following forms can be distinguished:

Infantile type , synonym: HSD10 deficiency, classic type
Neonatal type
Atypical form , synonym: X-linked syndromic intellectual disability type 10

Clinical manifestations

Clinical criteria are:

The changes affect several organ systems (multisystemic)
In the infantile form, cardiomyopathy , sometimes leading to early death, may be associated.
Forms with changes only in adolescence or diseases without neurological abnormalities can occur.
In more severe cases, developmental regression , often with seizures , choreoathetosis , spastic tetraplegia , optic atrophy or degeneration of the retina and intellectual disability, can occur.

In women affected, there may be non-progressive developmental delay and mental impairment or normal development.

diagnosis

In urine increased 2-methyl-3-hydroxybutyrate and Tiglylglyzin can be detected in blood serum , a lactic acidosis are present.

literature

S. Akagawa, T. Fukao, Y. Akagawa, H. Sasai, U. Kohdera, M. Kino, Y. Shigematsu, Y. Aoyama, K. Kaneko: Japanese Male Siblings with 2-Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency (HSD10 Disease) Without Neurological Regression. In: JIMD reports. Vol. 32, 2017, pp. 81–85, doi : 10.1007 / 8904_2016_570 , PMID 27306202 , PMC 5362553 (free full text).
E. Vilardo, W. Rossmanith: Molecular insights into HSD10 disease: impact of SDR5C1 mutations on the human mitochondrial RNase P complex. In: Nucleic acids research. Vol. 43, No. 13, July 2015, p. 6649, doi: 10.1093 / nar / gkv658 , PMID 26092698 , PMC 4513883 (free full text).
KC Chatfield, CR Coughlin, MW Friederich, RC Gallagher, JR Hesselberth, MA Lovell, R. Ofman, MA Swanson, JA Thomas, RJ Wanders, EP Wartchow, JL Van Hove: Mitochondrial energy failure in HSD10 disease is due to defective mtDNA transcript processing. In: Mitochondrion. Vol. 21, March 2015, pp. 1–10, doi: 10.1016 / j.mito.2014.12.005 , PMID 25575635 , PMC 4355277 (free full text)

Individual evidence

↑ ^a ^b HSD10 disease. In: Orphanet (Rare Disease Database).
↑ J. Zschocke, JP Ruiter, J. Brand, M. Lindner, GF Hoffmann, RJ Wanders, E. Mayatepek: Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched- chain fatty acid and isoleucine metabolism. In: Pediatric research. Vol. 48, No. 6, December 2000, pp. 852-855, doi: 10.1203 / 00006450-200012000-00025 , PMID 11102558 .
↑ ^a ^b HSD10 mitochondrial disease. In: Online Mendelian Inheritance in Man . (English)
↑ Genetics Home Reference HSD17B10
↑ HSD10 disease, infantile type. In: Orphanet (Rare Disease Database).
↑ HSD10 disease, neonatal type. In: Orphanet (Rare Disease Database).
↑ HSD10 deficiency, atypical form. In: Orphanet (Rare Disease Database).
↑ J. Zschocke: HSD10 disease: clinical consequences of mutations in the HSD17B10 gene. In: Journal of inherited metabolic disease. Vol. 35, No. 1, January 2012, pp. 81-89, doi: 10.1007 / s10545-011-9415-4 , PMID 22127393 (review).

Web links

Genetics Home Reference

[Orpha-1] HSD10 disease. In: Orphanet (Rare Disease Database).

[2] J. Zschocke, JP Ruiter, J. Brand, M. Lindner, GF Hoffmann, RJ Wanders, E. Mayatepek: Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched- chain fatty acid and isoleucine metabolism. In: Pediatric research. Vol. 48, No. 6, December 2000, pp. 852-855, doi: 10.1203 / 00006450-200012000-00025 , PMID 11102558 .

[OMIM-3] HSD10 mitochondrial disease. In: Online Mendelian Inheritance in Man . (English)

[4] Genetics Home Reference HSD17B10

[5] HSD10 disease, infantile type. In: Orphanet (Rare Disease Database).

[6] HSD10 disease, neonatal type. In: Orphanet (Rare Disease Database).

[7] HSD10 deficiency, atypical form. In: Orphanet (Rare Disease Database).

[8] J. Zschocke: HSD10 disease: clinical consequences of mutations in the HSD17B10 gene. In: Journal of inherited metabolic disease. Vol. 35, No. 1, January 2012, pp. 81-89, doi: 10.1007 / s10545-011-9415-4 , PMID 22127393 (review).