Format

Send to:

Choose Destination

Leukodystrophy, hypomyelinating, 4(HLD4)

MedGen UID:
383026
Concept ID:
C2677109
Disease or Syndrome
Synonyms: HLD4; MITCHAP60 DISEASE; MITOCHONDRIAL HSP60 CHAPERONOPATHY
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): HSPD1 (2q33.1)
OMIM®: 612233
Orphanet: ORPHA280288

Clinical features

From HPO
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
A group of rare genetic neurodegenerative disorders that affect infants and children. These disorders are characterized by metabolic abnormalities in the development of the myelin sheaths in the white matter. Clinical signs and symptoms include developmental delays, mental retardation, dementia, seizures, loss of motor skills, and muscle weakness. Representative examples include metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
A reflex characterized by upward movement of the great toe and an outward movement of the rest of the toes, when the sole of the foot is stroked. It is a normal reflex up to the age of two. Its presence beyond that age indicates neurological damage.
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Abnormal movement characterized by involuntary jerking and writhing affecting the limbs, trunk, and facial muscles.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Autonomic nervous system overreaction to stimuli, most commonly after spinal cord injury at a T-5 level and above.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Postnatal microcephaly
MedGen UID:
339779
Concept ID:
C1847514
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Progressive spasticity
MedGen UID:
347171
Concept ID:
C1859520
Finding
Spasticity that increases in degree with time.
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
A transient absence of spontaneous respiration.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Finding
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Progressive spasticity
MedGen UID:
347171
Concept ID:
C1859520
Finding
Spasticity that increases in degree with time.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Finding
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Postnatal microcephaly
MedGen UID:
339779
Concept ID:
C1847514
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Postnatal microcephaly
MedGen UID:
339779
Concept ID:
C1847514
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Finding
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLeukodystrophy, hypomyelinating, 4
Follow this link to review classifications for Leukodystrophy, hypomyelinating, 4 in Orphanet.

Recent clinical studies

Etiology

Miyamoto Y, Eguchi T, Kawahara K, Hasegawa N, Nakamura K, Funakoshi-Tago M, Tanoue A, Tamura H, Yamauchi J
Biochem Biophys Res Commun 2015 Jul 3;462(3):275-81. Epub 2015 May 6 doi: 10.1016/j.bbrc.2015.04.132. PMID: 25957474
Wolf NI, Vanderver A, van Spaendonk RM, Schiffmann R, Brais B, Bugiani M, Sistermans E, Catsman-Berrevoets C, Kros JM, Pinto PS, Pohl D, Tirupathi S, Strømme P, de Grauw T, Fribourg S, Demos M, Pizzino A, Naidu S, Guerrero K, van der Knaap MS, Bernard G; 4H Research Group.
Neurology 2014 Nov 18;83(21):1898-905. Epub 2014 Oct 22 doi: 10.1212/WNL.0000000000001002. PMID: 25339210Free PMC Article

Diagnosis

Cayami FK, Bugiani M, Pouwels PJW, Bernard G, van der Knaap MS, Wolf NI
Neuropediatrics 2018 Apr;49(2):112-117. Epub 2017 Nov 27 doi: 10.1055/s-0037-1608780. PMID: 29179231
Jurkiewicz E, Dunin-Wąsowicz D, Gieruszczak-Białek D, Malczyk K, Guerrero K, Gutierrez M, Tran L, Bernard G
Clin Neuroradiol 2017 Jun;27(2):213-220. Epub 2015 Oct 19 doi: 10.1007/s00062-015-0472-1. PMID: 26478204Free PMC Article
Wolf NI, Vanderver A, van Spaendonk RM, Schiffmann R, Brais B, Bugiani M, Sistermans E, Catsman-Berrevoets C, Kros JM, Pinto PS, Pohl D, Tirupathi S, Strømme P, de Grauw T, Fribourg S, Demos M, Pizzino A, Naidu S, Guerrero K, van der Knaap MS, Bernard G; 4H Research Group.
Neurology 2014 Nov 18;83(21):1898-905. Epub 2014 Oct 22 doi: 10.1212/WNL.0000000000001002. PMID: 25339210Free PMC Article

Prognosis

Jurkiewicz E, Dunin-Wąsowicz D, Gieruszczak-Białek D, Malczyk K, Guerrero K, Gutierrez M, Tran L, Bernard G
Clin Neuroradiol 2017 Jun;27(2):213-220. Epub 2015 Oct 19 doi: 10.1007/s00062-015-0472-1. PMID: 26478204Free PMC Article
Wolf NI, Vanderver A, van Spaendonk RM, Schiffmann R, Brais B, Bugiani M, Sistermans E, Catsman-Berrevoets C, Kros JM, Pinto PS, Pohl D, Tirupathi S, Strømme P, de Grauw T, Fribourg S, Demos M, Pizzino A, Naidu S, Guerrero K, van der Knaap MS, Bernard G; 4H Research Group.
Neurology 2014 Nov 18;83(21):1898-905. Epub 2014 Oct 22 doi: 10.1212/WNL.0000000000001002. PMID: 25339210Free PMC Article

Clinical prediction guides

Jurkiewicz E, Dunin-Wąsowicz D, Gieruszczak-Białek D, Malczyk K, Guerrero K, Gutierrez M, Tran L, Bernard G
Clin Neuroradiol 2017 Jun;27(2):213-220. Epub 2015 Oct 19 doi: 10.1007/s00062-015-0472-1. PMID: 26478204Free PMC Article
Wolf NI, Vanderver A, van Spaendonk RM, Schiffmann R, Brais B, Bugiani M, Sistermans E, Catsman-Berrevoets C, Kros JM, Pinto PS, Pohl D, Tirupathi S, Strømme P, de Grauw T, Fribourg S, Demos M, Pizzino A, Naidu S, Guerrero K, van der Knaap MS, Bernard G; 4H Research Group.
Neurology 2014 Nov 18;83(21):1898-905. Epub 2014 Oct 22 doi: 10.1212/WNL.0000000000001002. PMID: 25339210Free PMC Article

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center