Holocarboxylase synthetase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: MULTIPLE CARBOXYLASE DEFICIENCY, EARLY ONSET
MULTIPLE CARBOXYLASE DEFICIENCY, NEONATAL FORM
HLCS DEFICIENCY
Neonatal multiple carboxylase deficiency
Early-onset multiple carboxylase deficiency
Number of Symptoms 35
OrphanetNr: 79242
OMIM Id: 253270
ICD-10: E53.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Multiple carboxylase deficiency
 -Rare genetic disease
 -Rare skin disease

Symptom Information: Sort by abundance 

1
 (HPO:0001992) Organic aciduria 28 / 7739
2
 (HPO:0100825) Cheilitis Very frequent [Orphanet] 20 / 7739
3
 (HPO:0100533) Inflammatory abnormality of the eye Very frequent [Orphanet] 70 / 7739
4
 (HPO:0001254) Lethargy 104 / 7739
5
 (HPO:0000737) Irritability 93 / 7739
6
 (HPO:0001259) Coma 65 / 7739
7
 (HPO:0004372) Reduced consciousness/confusion Occasional [Orphanet] 73 / 7739
8
 (HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
9
 (HPO:0100851) Abnormal emotion/affect behavior Very frequent [Orphanet] 85 / 7739
10
 (HPO:0002066) Gait ataxia Occasional [Orphanet] 327 / 7739
11
 (HPO:0001276) Hypertonia 317 / 7739
12
 (HPO:0001263) Global developmental delay 853 / 7739
13
 (HPO:0008872) Feeding difficulties in infancy 153 / 7739
14
 (HPO:0002017) Nausea and vomiting Very frequent [Orphanet] 134 / 7739
15
 (HPO:0002013) Vomiting 191 / 7739
16
 (HPO:0011968) Feeding difficulties 240 / 7739
17
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
18
 (HPO:0001596) Alopecia Occasional [Orphanet] 162 / 7739
19
 (HPO:0000988) Skin rash 98 / 7739
20
 (HPO:0000958) Dry skin Occasional [Orphanet] 152 / 7739
21
 (HPO:0001873) Thrombocytopenia Occasional [Orphanet] 224 / 7739
22
 (HPO:0001987) Hyperammonemia Frequent [Orphanet] 50 / 7739
23
 (HPO:0001942) Metabolic acidosis 81 / 7739
24
 (HPO:0002883) Hyperventilation 10 / 7739
25
 (HPO:0002793) Abnormal pattern of respiration Frequent [Orphanet] 26 / 7739
26
 (HPO:0002789) Tachypnea 48 / 7739
27
 (HPO:0002093) Respiratory insufficiency Frequent [Orphanet] 410 / 7739
28
 (HPO:0001252) Muscular hypotonia Very frequent [Orphanet] 990 / 7739
29
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
30
 (HPO:0010547) Muscle flaccidity 466 / 7739
31
 (HPO:0001324) Muscle weakness 859 / 7739
32
 (OMIM) Holocarboxylase synthetase deficiency 1 / 7739
33
 (OMIM) Normal serum biotin concentration 1 / 7739
34
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
35
 (OMIM) Mild-moderate hyperammonemia 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Early-onset multiple carboxylase deficiency, or holocarboxylase deficiency, is an autosomal recessive disorder of biotin metabolism. See also late-onset or juvenile MCD (253260) caused by mutation in the biotinidase gene (BTD; 609019). Sweetman (1981) recognized that multiple carboxylase deficiency ...
Clinical Description OMIM Thoene et al. (1979) described a child with decreased activity of 3 biotin-dependent carboxylases: pyruvate carboxylase (PCC; 608786), propionyl CoA carboxylase (PCCA; 232000), and alpha-methylcrotonyl CoA carboxylase (MCCC1; 609010). The severe manifestations included lactic acidosis, alopecia, keratoconjunctivitis, perioral ...
Molecular genetics OMIM In sibs with HLCS deficiency reported by Narisawa et al. (1982), Suzuki et al. (1994) demonstrated compound heterozygosity for 2 mutations in the HLCS gene (609018.0001; 609018.0002).

In 9 patients with multiple carboxylase deficiency, Dupuis et ...