Details of Disease

General Information of Disease (ID: DIS9OPZ4)

• Disease Name: Systemic primary carnitine deficiency disease
• Synonyms: CARNITINE deficiency, systemic primary; Carnitine deficiency, systemic, due to defect in renal reabsorption of Carnitine; systemic primary carnitine deficiency; Carnitine transporter, plasma-Membrane, deficiency of; Carnitine deficiency, systemic, due to defect in renal reabsorption of carnitine; Carnitine uptake defect; Carnitine plasma-membrane transporter deficiency; systemic Carnitine deficiency; Carnitine deficiency, primary; Carnitine deficiency; primary carnitine deficiency; carnitine uptake defect; cud; Carnitine transporter defect; CDSP; carnitine transporter deficiency; SPCD; renal carnitine transport defect; systemic primary carnitine deficiency disease; deficiency of plasma-membrane carnitine transporter; Carnitine uptake deficiency
• Definition: Systemic primary carnitine deficiency (SPCD) is a potentially lethal disorder of fatty acid oxidation characterized classically by early childhood onset cardiomyopathy often with weakness and hypotonia, failure to thrive and recurrent hypoglycemic hypoketotic seizures and/or coma.
• Disease Hierarchy:
  DISXOOWI: Disorder of carnitine cycle and carnitine transport
  DISA6JBV: Disorder of fatty acid oxidation and ketogenesis
  DIS9OPZ4: Systemic primary carnitine deficiency disease
• Disease Identifiers:
  MONDO ID: MONDO_0008919
  MESH ID: C536778
  UMLS CUI: C0342788
  OMIM ID: 212140
  MedGen ID: 90999
  Orphanet ID: 158
  SNOMED CT ID: 21764004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CPT1B	TTDL0NY	Limited	Genetic Variation	[1]
DAGLA	TTRQ6UD	Limited	Biomarker	[2]
DAGLB	TTXZDEN	Limited	Biomarker	[2]
DLL3	TT1C9K6	Limited	Biomarker	[3]
CACNA1C	TTZIFHC	Strong	Biomarker	[4]
SCD	TT6RIOV	Strong	Biomarker	[5]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC22A4	DT2EG60	Limited	Biomarker	[6]
SLC22A5	DT3HUVD	Definitive	Autosomal recessive	[7]

This Disease Is Related to 22 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ABHD5	OTY829Z3	Limited	Biomarker	[8]
ACADM	OTA4P0FC	Limited	Genetic Variation	[9]
BEAN1	OT0WLH27	Limited	Biomarker	[10]
BRAP	OTB7BAFQ	Limited	Biomarker	[11]
CDH23	OTOJGQ7S	Limited	Genetic Variation	[12]
DMRT2	OTA39QNR	Limited	Genetic Variation	[13]
ETFB	OT6Q6FBD	Limited	Biomarker	[8]
ETFDH	OTOSKSFH	Limited	Biomarker	[8]
GZMM	OTEC5CWT	Limited	Biomarker	[13]
IMPA1	OTBUVW1Z	Limited	Biomarker	[11]
INSIG1	OTZF5X1D	Limited	Genetic Variation	[14]
LFNG	OTPSUBN2	Limited	Genetic Variation	[15]
MADD	OTUFYVGG	Limited	Biomarker	[16]
MESP2	OT7H4LYA	Limited	Biomarker	[17]
RIPPLY2	OTDEEDLH	Limited	Biomarker	[13]
SAR1A	OTSSRVGV	Limited	Biomarker	[18]
SCD5	OTSSUQ3Z	Limited	Biomarker	[19]
TBX6	OTW1Q8RM	Limited	Biomarker	[20]
TK2	OTS1V4XB	Limited	Biomarker	[10]
TMLHE	OTH4ZLJP	Limited	Biomarker	[21]
HES7	OT6F9R7P	Definitive	Genetic Variation	[22]
SLC22A5	OTC36TYB	Definitive	Autosomal recessive	[7]

References

• [1] Follow-up of fatty acid -oxidation disorders in expanded newborn screening era.Eur J Pediatr. 2019 Mar;178(3):387-394. doi: 10.1007/s00431-018-03315-2. Epub 2019 Jan 7.
• [2] Genetic variation in FAAH is associated with cannabis use disorders in a young adult sample of Mexican Americans.Drug Alcohol Depend. 2016 Sep 1;166:249-53. doi: 10.1016/j.drugalcdep.2016.06.021. Epub 2016 Jun 25.
• [3] Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis.Hum Mol Genet. 2011 Mar 1;20(5):905-16. doi: 10.1093/hmg/ddq529. Epub 2010 Dec 7.
• [4] Emerging therapeutic targets in the short QT syndrome.Expert Opin Ther Targets. 2018 May;22(5):439-451. doi: 10.1080/14728222.2018.1470621.
• [5] Diagnostics of DNA fragmentation in human spermatozoa: Are sperm chromatin structure analysis and sperm chromatin dispersion tests (SCD-HaloSpermG2() ) comparable?.Andrologia. 2019 Sep;51(8):e13316. doi: 10.1111/and.13316. Epub 2019 May 17.
• [6] Genotype-phenotype correlation in primary carnitine deficiency.Hum Mutat. 2012 Jan;33(1):118-23. doi: 10.1002/humu.21607. Epub 2011 Oct 11.
• [7] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [8] Clinical and genetic analysis of lipid storage myopathies.Muscle Nerve. 2009 Mar;39(3):333-42. doi: 10.1002/mus.21167.
• [9] Clinical and genetic characteristics of patients with fatty acid oxidation disorders identified by newborn screening.BMC Pediatr. 2018 Mar 8;18(1):103. doi: 10.1186/s12887-018-1069-z.
• [10] Impaired Adaptive Motor Learning Is Correlated With Cerebellar Hemispheric Gray Matter Atrophy in Spinocerebellar Ataxia Patients: A Voxel-Based Morphometry Study.Front Neurol. 2019 Nov 14;10:1183. doi: 10.3389/fneur.2019.01183. eCollection 2019.
• [11] Arterial spin labeling MR imaging for the clinical detection of cerebellar hypoperfusion in patients with spinocerebellar degeneration.J Neurol Sci. 2018 Nov 15;394:58-62. doi: 10.1016/j.jns.2018.09.007. Epub 2018 Sep 6.
• [12] CDH23 Related Hearing Loss: A New Genetic Risk Factor for Semicircular Canal Dehiscence?.Otol Neurotol. 2016 Dec;37(10):1583-1588. doi: 10.1097/MAO.0000000000001210.
• [13] Homozygous DMRT2 variant associates with severe rib malformations in a newborn.Am J Med Genet A. 2018 May;176(5):1216-1221. doi: 10.1002/ajmg.a.38668.
• [14] Schnyder corneal dystrophy-associated UBIAD1 mutations cause corneal cholesterol accumulation by stabilizing HMG-CoA reductase.PLoS Genet. 2019 Jul 19;15(7):e1008289. doi: 10.1371/journal.pgen.1008289. eCollection 2019 Jul.
• [15] Screening of known disease genes in congenital scoliosis.Mol Genet Genomic Med. 2018 Nov;6(6):966-974. doi: 10.1002/mgg3.466. Epub 2018 Sep 9.
• [16] Spectrum of metabolic myopathies.Biochim Biophys Acta. 2015 Apr;1852(4):615-21. doi: 10.1016/j.bbadis.2014.06.031. Epub 2014 Jul 2.
• [17] Defective somitogenesis and abnormal vertebral segmentation in man.Adv Exp Med Biol. 2008;638:164-89. doi: 10.1007/978-0-387-09606-3_9.
• [18] The Responsiveness of Triaxial Accelerometer Measurement of Gait Ataxia Is Higher than That of the Scale for the Assessment and Rating of Ataxia in the Early Stages of Spinocerebellar Degeneration.Cerebellum. 2019 Aug;18(4):721-730. doi: 10.1007/s12311-019-01025-5.
• [19] Ciliary ultrastructure in patients with chronic rhinosinusitis and primary ciliary dyskinesia.Eur Arch Otorhinolaryngol. 2013 Jul;270(7):2065-70. doi: 10.1007/s00405-012-2342-7. Epub 2013 Jan 5.
• [20] Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.J Med Genet. 2019 Sep;56(9):622-628. doi: 10.1136/jmedgenet-2018-105920. Epub 2019 Apr 22.
• [21] Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias: A hypothesis.Bioessays. 2017 Aug;39(8):10.1002/bies.201700012. doi: 10.1002/bies.201700012. Epub 2017 Jul 13.
• [22] Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis.Eur J Hum Genet. 2010 Jun;18(6):674-9. doi: 10.1038/ejhg.2009.241. Epub 2010 Jan 20.