eRAM
encyclopedia of Rare Disease Annotation for Precision Medicine
| holocarboxylase synthetase deficiency | ||||
| Disease ID | 334 |
|---|---|
| Disease | holocarboxylase synthetase deficiency |
| Definition | A rare autosomal recessive inherited disorder caused by mutations in the HLCS gene. It is characterized by deficiency of the enzyme holocarboxylase synthetase which facilitates the effective use of the vitamin biotin in the body. Signs and symptoms appear early in life and include breathing difficulties, feeding difficulties, alopecia, skin rash, and lethargy. Lifelong administration of biotin supplements is required. If it is not treated properly, it may lead to developmental delays, seizures, and coma. |
| Synonym | biotin-(propionyl-coa-carboxylase) ligase deficiency biotin-(propionyl-coa-carboxylase) ligase deficiency (disorder) biotin-(propionyl-coenzyme a-carboxylase) ligase deficiency biotin-(propionyl-coenzyme a-carboxylase) ligase deficiency (disorder) carboxylase defic multiple neonatal form carboxylase deficiency, multiple, neonatal form defic holocarboxylase synthetase defic multiple carboxylase neonatal form deficiencies, hlcs deficiencies, holocarboxylase synthetase deficiency, hlcs deficiency, holocarboxylase synthetase deficiency, multiple carboxylase, neonatal form early onset biotin responsive multiple carboxylase deficiency early onset combined carboxylase deficiency early-onset biotin-responsive multiple carboxylase deficiency early-onset combined carboxylase deficiency hlcs deficiencies hlcs deficiency holocarboxylase synthase deficiency holocarboxylase synthase deficiency (disorder) holocarboxylase synthase deficiency [ambiguous] holocarboxylase synthetase defic holocarboxylase synthetase deficiencies holocarboxylase synthetase deficiency [disease/finding] infantile multiple carboxylase deficiency multiple carboxylase defic neonatal form multiple carboxylase deficiency - neonatal onset multiple carboxylase deficiency - neonatal onset (disorder) multiple carboxylase deficiency, early onset multiple carboxylase deficiency, neonatal form multiple carboxylase deficiency, neonatal onset neonatal biotin-responsive multiple carboxylase deficiency neonatal holocarboxylase synthetase deficiency neonatal multiple carboxylase deficiency |
| Orphanet | |
| OMIM | |
| DOID | |
| UMLS | C0268581 |
| MeSH | |
| SNOMED-CT | |
| Curated Gene | Entrez_id | Symbol | Resource(Total Genes:1) |
| Inferring Gene | (Waiting for update.) |
| Text Mined Gene | Entrez_id | Symbol | Score | Resource(Total Genes:6) |
| Locus | Symbol | Locus(Total Locus:1) HLCS | 21q22.13 |
| Disease ID | 334 |
|---|---|
| Disease | holocarboxylase synthetase deficiency |
| Integrated Phenotype | HPO | Name(Total Integrated Phenotypes:30) HP:0001987 | Hyperammonemia HP:0002789 | Tachypnea HP:0001824 | Weight loss HP:0002789 | Increased respiratory rate or depth of breathing HP:0001992 | Organic aciduria HP:0002098 | Respiratory distress HP:0000988 | Exanthem HP:0001251 | Ataxia HP:0001873 | Thrombocytopenia HP:0001254 | Lethargy HP:0002017 | Nausea and vomiting HP:0001276 | Hypertonia HP:0001510 | Growth delay HP:0008872 | Feeding difficulties in infancy HP:0001252 | Hypotonia HP:0001250 | Seizures HP:0001942 | Metabolic acidosis HP:0001263 | Developmental retardation HP:0011127 | Perioral eczema HP:0001259 | Coma HP:0001873 | Low platelet count HP:0001596 | Hair loss HP:0002883 | Rapid breathing HP:0001596 | Alopecia HP:0000737 | Irritability HP:0000964 | Eczema HP:0001252 | Muscular hypotonia HP:0001096 | Keratoconjunctivitis HP:0002013 | Emesis HP:0002039 | Anorexia |
| Text Mined Phenotype | (Waiting for update.) |
| Disease ID | 334 |
|---|---|
| Disease | holocarboxylase synthetase deficiency |
| Manually Symptom | (Waiting for update.) |
| Text Mined Symptom | (Waiting for update.) |
Manually Genotype(Total Text Mining Genotypes:0) |
|---|
| (Waiting for update.) |
Text Mining Genotype(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
All Snps(Total Genotypes:13) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| snpId | pubmedId | geneId | geneSymbol | diseaseId | sourceId | sentence | score | Year | geneSymbol_dbSNP | CHROMOSOME | POS | REF | ALT |
| rs119103227 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36936735 | A | G |
| rs119103228 | 10190325 | 3141 | HLCS | umls:C0268581 | UNIPROT | These data suggest that a variety of mutations is responsible for decreasing HCS activity and that the aspartate residue at amino acid position 571 may be crucial for the catalytic activity of HCS. | 0.480271442 | 1999 | HLCS | 21 | 36759811 | C | T |
| rs119103228 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36759811 | C | T |
| rs119103229 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36765170 | G | A |
| rs119103230 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36759781 | C | T |
| rs119103231 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36765044 | C | T |
| rs149399432 | 12633764 | 3141 | HLCS | umls:C0268581 | UNIPROT | Multiple carboxylase deficiency (MCD, MIM:253270) is a common organic aciduria and caused by deficiency of either biotinidase or holocarboxylase synthetase (HLCS; EC 6.3.4.10). | 0.480271442 | 2003 | HLCS | 21 | 36756651 | C | T |
| rs28934602 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36936798 | A | C |
| rs28934602 | 18429047 | 3141 | HLCS | umls:C0268581 | UNIPROT | Multiple carboxylase deficiency is a clinical condition caused by defects in the enzymes involved in biotin metabolism, holocarboxylase synthetase (HLCS) or biotinidase. | 0.480271442 | 2008 | HLCS | 21 | 36936798 | A | C |
| rs376899782 | 12124727 | 3141 | HLCS | umls:C0268581 | UNIPROT | Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. | 0.480271442 | 2002 | HLCS | 21 | 36759778 | C | T |
| rs753887925 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36767213 | C | T |
| rs773102942 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36936789 | - | T |
| rs794727957 | NA | 3141 | HLCS | umls:C0268581 | CLINVAR | NA | 0.480271442 | NA | HLCS | 21 | 36765068 | G | A |
GWASdb Annotation(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
GWASdb Snp Trait(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
Mapped by lexical matching(Total Items:7) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0008872 | Feeding difficulties in infancy | MP:0011075 | abnormal macrophage activation involved in immune response | anomaly in the process in which a change in response and behavior of a macrophage results from exposure to a cytokine, chemokine, cellular ligand, or soluble factor, leading to the initiation or perpetuation of an immune response |
| HP:0001263 | Global developmental delay | MP:0002084 | abnormal developmental patterning | abnormal systematic arrangement of the developing body along an axis |
| HP:0001942 | Metabolic acidosis | MP:0012551 | metabolic acidosis | decreased pH and bicarbonate concentration in tissues and/or body fluids caused when the body produces too much acid or when the kidneys are not removing enough acid from the body, as in diarrhea or in kidney disease |
| HP:0002098 | Respiratory distress | MP:0001954 | respiratory distress | physical difficulty or inability to breathe; shortness of breath |
| HP:0001252 | Muscular hypotonia | MP:0004144 | hypotonia | decreased muscle tension resulting in limpness of the muscles in the resting state, not to be confused with weakness |
| HP:0002017 | Nausea and vomiting | MP:0010426 | abnormal heart and great artery attachment | any anomaly in the in the position or pattern of the connection site of the heart to any of the great arteries, including the pulmonary artery and aorta |
| HP:0001824 | Weight loss | MP:0005114 | premature hair loss | release of fur at an earlier than expected time |
Mapped by homologous gene(Total Items:26) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0001252 | Muscular hypotonia | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| HP:0002098 | Respiratory distress | MP:0014198 | absent pituitary infundibular stalk | absence of the apical portion of the tubular structure extending from the hypothalamus to the posterior lobe of the pituitary gland |
| HP:0001250 | Seizures | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| HP:0001259 | Coma | MP:0020216 | decreased circulating complement protein level | less than normal levels of the serum proteins that act sequentially to allow for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes |
| HP:0000964 | Eczema | MP:0020154 | impaired humoral immune response | impaired response of the immune system that mediates secreted antibodies produced in B cells |
| HP:0001096 | Keratoconjunctivitis | MP:0020220 | decreased tear production | decreased production of the amount of fluid produced in the eye |
| HP:0002883 | Hyperventilation | MP:0014178 | increased brain apoptosis | increase in the number of cells of the brain undergoing programmed cell death |
| HP:0001510 | Growth delay | MP:0020169 | increased thyroid gland weight | higher than average weight of the thyroid gland |
| HP:0001873 | Thrombocytopenia | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0002017 | Nausea and vomiting | MP:0020220 | decreased tear production | decreased production of the amount of fluid produced in the eye |
| HP:0001992 | Organic aciduria | MP:0011471 | decreased urine creatinine level | a reduced amount of creatinine in the urine compared to the normal state |
| HP:0002039 | Anorexia | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0011127 | Perioral eczema | MP:0013799 | abnormal intestinal goblet cell physiology | any functional anomaly of the glandular simple columnar epithelial cell found in the mucosal lining of the small and large intestine, whose primary function is to secrete gel-forming mucins, the major components of mucus; intestinal goblet cells produce a |
| HP:0000737 | Irritability | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0001824 | Weight loss | MP:0020220 | decreased tear production | decreased production of the amount of fluid produced in the eye |
| HP:0001263 | Global developmental delay | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| HP:0001276 | Hypertonia | MP:0020316 | decreased vascular endothelial cell proliferation | decrease in the expansion rate of any vascular endothelial cell population by cell division |
| HP:0001254 | Lethargy | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0002789 | Tachypnea | MP:0013572 | abnormal parathyroid gland chief cell morphology | any structural anomaly of an epithelial cell that are collectively arranged in wide, irregular interconnecting columns in the parathyroid gland, that is responsible for the synthesis and secretion of parathyroid hormone (PTH) |
| HP:0001251 | Ataxia | MP:0020301 | short tongue | decreased length of the mobile mass of muscular tissue and surrounding epithelial tissue occupying the cavity of the mouth and forming part of the floor |
| HP:0008872 | Feeding difficulties in infancy | MP:0020214 | susceptible to malignant hyperthermia | increased susceptibility to hyperthermia triggered by exposure to certain drugs used for general anesthesia, specifically the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine |
| HP:0001987 | Hyperammonemia | MP:0013405 | increased circulating lactate level | greater amount of lactate in the blood which is produced from pyruvate by lactate dehydrogenase |
| HP:0002013 | Vomiting | MP:0020316 | decreased vascular endothelial cell proliferation | decrease in the expansion rate of any vascular endothelial cell population by cell division |
| HP:0001942 | Metabolic acidosis | MP:0014206 | decreased intestinal epithelial sodium ion transmembrane transport | |
| HP:0001596 | Alopecia | MP:0020220 | decreased tear production | decreased production of the amount of fluid produced in the eye |
| HP:0000988 | Skin rash | MP:0020154 | impaired humoral immune response | impaired response of the immune system that mediates secreted antibodies produced in B cells |
| Disease ID | 334 |
|---|---|
| Disease | holocarboxylase synthetase deficiency |
| Case | (Waiting for update.) |