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DK1-congenital disorder of glycosylation(CDGIm; CDG1M)

MedGen UID:
332072
Concept ID:
C1835849
Disease or Syndrome
Synonyms: Carbohydrate deficient glycoprotein syndrome type 1m; CDG Im; Congenital disorder of glycosylation type 1M; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im; DK1 DEFICIENCY; DK1-CDG; DOLICHOL KINASE DEFICIENCY; DOLK-CDG (CDG-Im); DOLK-congenital disorder of glycosylation
SNOMED CT: Carbohydrate deficient glycoprotein syndrome type 1m (718712005); Carbohydrate deficient glycoprotein syndrome type Im (718712005); CDG1M - carbohydrate deficient glycoprotein syndrome type 1m (718712005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): DOLK (9q34.11)
 
Monarch Initiative: MONDO:0012556
OMIM®: 610768
Orphanet: ORPHA91131

Definition

DOLK-congenital disorder of glycosylation (DOLK-CDG, formerly known as congenital disorder of glycosylation type Im) is an inherited condition that often affects the heart but can also involve other body systems. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.

Individuals with DOLK-CDG typically develop signs and symptoms of the condition during infancy or early childhood. Nearly all individuals with DOLK-CDG develop a weakened and enlarged heart (dilated cardiomyopathy). Other frequent signs and symptoms include recurrent seizures; developmental delay; poor muscle tone (hypotonia); and dry, scaly skin (ichthyosis). Less commonly, affected individuals can have distinctive facial features, kidney disease, hormonal abnormalities, or eye problems.

Individuals with DOLK-CDG typically do not survive into adulthood, often because of complications related to dilated cardiomyopathy, and some do not survive past infancy. [from MedlinePlus Genetics]

Clinical features

From HPO
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Bradycardia
MedGen UID:
140901
Concept ID:
C0428977
Finding
A slower than normal heart rate (in adults, slower than 60 beats per minute).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Tetraplegia
MedGen UID:
19617
Concept ID:
C0034372
Disease or Syndrome
Paralysis of all four limbs, and trunk of the body below the level of an associated injury to the spinal cord. The etiology of quadriplegia is similar to that of paraplegia except that the lesion is in the cervical spinal cord rather than in the thoracic or lumbar segments of the spinal cord.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Secondary microcephaly
MedGen UID:
608952
Concept ID:
C0431352
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Aspiration
MedGen UID:
751786
Concept ID:
C2712334
Finding
Inspiration of a foreign object into the airway.
Inflammatory abnormality of the skin
MedGen UID:
849741
Concept ID:
C3875321
Disease or Syndrome
The presence of inflammation of the skin. That is, an abnormality of the skin resulting from the local accumulation of fluid, plasma proteins, and leukocytes.
Type I transferrin isoform profile
MedGen UID:
324900
Concept ID:
C1837899
Finding
Abnormal transferrin isoform profile consistent with a type I congenital disorder of glycosylation. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II.
Hypoketotic hypoglycemia
MedGen UID:
344733
Concept ID:
C1856438
Finding
A decreased concentration of glucose in the blood associated with a reduced concentration of ketone bodies.
Increased circulating free fatty acid level
MedGen UID:
908805
Concept ID:
C4280773
Finding
A higher than normal levels of the fatty acids which can occur in plasma as a result of lipolysis in adipose tissue or when plasma triacyglycerols are taken into tissues.
Sparse eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number of eyebrow hairs.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Hyperkeratosis
MedGen UID:
209030
Concept ID:
C0870082
Disease or Syndrome
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
Sparse eyelashes
MedGen UID:
375151
Concept ID:
C1843300
Finding
Decreased density/number of eyelashes.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for DK1-congenital disorder of glycosylation in Orphanet.

Professional guidelines

PubMed

Mueller AL, Payandeh Z, Mohammadkhani N, Mubarak SMH, Zakeri A, Alagheband Bahrami A, Brockmueller A, Shakibaei M
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Med Princ Pract 2021;30(3):223-235. Epub 2020 Oct 9 doi: 10.1159/000512142. PMID: 33040057Free PMC Article
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Recent clinical studies

Etiology

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Int J Mol Sci 2020 Aug 6;21(16) doi: 10.3390/ijms21165630. PMID: 32781578Free PMC Article
Altassan R, Péanne R, Jaeken J, Barone R, Bidet M, Borgel D, Brasil S, Cassiman D, Cechova A, Coman D, Corral J, Correia J, de la Morena-Barrio ME, de Lonlay P, Dos Reis V, Ferreira CR, Fiumara A, Francisco R, Freeze H, Funke S, Gardeitchik T, Gert M, Girad M, Giros M, Grünewald S, Hernández-Caselles T, Honzik T, Hutter M, Krasnewich D, Lam C, Lee J, Lefeber D, Marques-de-Silva D, Martinez AF, Moravej H, Õunap K, Pascoal C, Pascreau T, Patterson M, Quelhas D, Raymond K, Sarkhail P, Schiff M, Seroczyńska M, Serrano M, Seta N, Sykut-Cegielska J, Thiel C, Tort F, Vals MA, Videira P, Witters P, Zeevaert R, Morava E
J Inherit Metab Dis 2019 Jan;42(1):5-28. doi: 10.1002/jimd.12024. PMID: 30740725
Jaeken J, Péanne R
J Inherit Metab Dis 2017 Jul;40(4):569-586. Epub 2017 May 8 doi: 10.1007/s10545-017-0050-6. PMID: 28484880

Diagnosis

Qing L, Li Q, Dong Z
Bull Cancer 2022 Nov;109(11):1202-1216. Epub 2022 Sep 30 doi: 10.1016/j.bulcan.2022.08.001. PMID: 36184332
Luo G, Jin K, Deng S, Cheng H, Fan Z, Gong Y, Qian Y, Huang Q, Ni Q, Liu C, Yu X
Biochim Biophys Acta Rev Cancer 2021 Apr;1875(2):188409. Epub 2020 Aug 19 doi: 10.1016/j.bbcan.2020.188409. PMID: 32827580
Altassan R, Péanne R, Jaeken J, Barone R, Bidet M, Borgel D, Brasil S, Cassiman D, Cechova A, Coman D, Corral J, Correia J, de la Morena-Barrio ME, de Lonlay P, Dos Reis V, Ferreira CR, Fiumara A, Francisco R, Freeze H, Funke S, Gardeitchik T, Gert M, Girad M, Giros M, Grünewald S, Hernández-Caselles T, Honzik T, Hutter M, Krasnewich D, Lam C, Lee J, Lefeber D, Marques-de-Silva D, Martinez AF, Moravej H, Õunap K, Pascoal C, Pascreau T, Patterson M, Quelhas D, Raymond K, Sarkhail P, Schiff M, Seroczyńska M, Serrano M, Seta N, Sykut-Cegielska J, Thiel C, Tort F, Vals MA, Videira P, Witters P, Zeevaert R, Morava E
J Inherit Metab Dis 2019 Jan;42(1):5-28. doi: 10.1002/jimd.12024. PMID: 30740725
Jaeken J, Péanne R
J Inherit Metab Dis 2017 Jul;40(4):569-586. Epub 2017 May 8 doi: 10.1007/s10545-017-0050-6. PMID: 28484880
Stowell SR, Ju T, Cummings RD
Annu Rev Pathol 2015;10:473-510. doi: 10.1146/annurev-pathol-012414-040438. PMID: 25621663Free PMC Article

Therapy

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Cancer Cell 2019 Jul 8;36(1):6-16. doi: 10.1016/j.ccell.2019.06.006. PMID: 31287993
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Prognosis

Stanczak MA, Rodrigues Mantuano N, Kirchhammer N, Sanin DE, Jacob F, Coelho R, Everest-Dass AV, Wang J, Trefny MP, Monaco G, Bärenwaldt A, Gray MA, Petrone A, Kashyap AS, Glatz K, Kasenda B, Normington K, Broderick J, Peng L, Pearce OMT, Pearce EL, Bertozzi CR, Zippelius A, Läubli H
Sci Transl Med 2022 Nov 2;14(669):eabj1270. doi: 10.1126/scitranslmed.abj1270. PMID: 36322632Free PMC Article
Qing L, Li Q, Dong Z
Bull Cancer 2022 Nov;109(11):1202-1216. Epub 2022 Sep 30 doi: 10.1016/j.bulcan.2022.08.001. PMID: 36184332
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Clinical prediction guides

Radovani B, Gudelj I
Front Immunol 2022;13:893365. Epub 2022 Jun 27 doi: 10.3389/fimmu.2022.893365. PMID: 35833138Free PMC Article
Dashti H, Pabon Porras MA, Mora S
Adv Exp Med Biol 2021;1325:307-319. doi: 10.1007/978-3-030-70115-4_15. PMID: 34495542
Luo G, Jin K, Deng S, Cheng H, Fan Z, Gong Y, Qian Y, Huang Q, Ni Q, Liu C, Yu X
Biochim Biophys Acta Rev Cancer 2021 Apr;1875(2):188409. Epub 2020 Aug 19 doi: 10.1016/j.bbcan.2020.188409. PMID: 32827580
Groux-Degroote S, Cavdarli S, Uchimura K, Allain F, Delannoy P
Adv Protein Chem Struct Biol 2020;119:111-156. Epub 2019 Nov 26 doi: 10.1016/bs.apcsb.2019.08.008. PMID: 31997767
Vogt G, Vogt B, Chuzhanova N, Julenius K, Cooper DN, Casanova JL
Curr Opin Genet Dev 2007 Jun;17(3):245-51. Epub 2007 Apr 30 doi: 10.1016/j.gde.2007.04.008. PMID: 17467977

Recent systematic reviews

Simpson TC, Clarkson JE, Worthington HV, MacDonald L, Weldon JC, Needleman I, Iheozor-Ejiofor Z, Wild SH, Qureshi A, Walker A, Patel VA, Boyers D, Twigg J
Cochrane Database Syst Rev 2022 Apr 14;4(4):CD004714. doi: 10.1002/14651858.CD004714.pub4. PMID: 35420698Free PMC Article
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Cochrane Database Syst Rev 2020 May 29;5(5):CD005266. doi: 10.1002/14651858.CD005266.pub2. PMID: 32470201Free PMC Article
Lin X, Zhang X, Guo J, Roberts CK, McKenzie S, Wu WC, Liu S, Song Y
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Yang Z, Scott CA, Mao C, Tang J, Farmer AJ
Sports Med 2014 Apr;44(4):487-99. doi: 10.1007/s40279-013-0128-8. PMID: 24297743
Leach MJ, Kumar S
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