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Leukodystrophy, hypomyelinating, 24(HLD24)

MedGen UID:
1805365
Concept ID:
C5676974
Disease or Syndrome
Synonym: HLD24
 
Gene (location): ATP11A (13q34)
 
Monarch Initiative: MONDO:0859242
OMIM®: 619851

Definition

Hypomyelinating leukodystrophy-24 (HLD24) is an autosomal dominant disorder characterized by global developmental delay and neurologic deterioration (Segawa et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. [from OMIM]

Clinical features

From HPO
Severe short stature
MedGen UID:
3931
Concept ID:
C0013336
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Widened subarachnoid space
MedGen UID:
375826
Concept ID:
C1846151
Finding
An increase in size of the anatomic space between the arachnoid membrane and pia mater.
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
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.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
An abnormal decrease from the normal count of B cells.
Tongue fasciculations
MedGen UID:
65987
Concept ID:
C0239548
Finding
Fasciculations or fibrillation affecting the tongue muscle.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Recent clinical studies

Etiology

Ashrafi M, Kameli R, Hosseinpour S, Razmara E, Zamani Z, Rezaei Z, Mashayekhi R, Pak N, Barzegar M, Azizimalamiri R, Kashani MR, Khosroshahi N, Rasulinezhad M, Heidari M, Amanat M, Abdi A, Mohammadi B, Mohammadi M, Zamani GR, Badv RS, Omrani A, Nikbakht S, Bereshneh AH, Movahedinia M, Moghaddam HF, Ardakani HS, Akbari MG, Tousi MB, Shahi MV, Hosseini F, Amouzadeh MH, Hosseini SA, Nikkhah A, Khajeh A, Alizadeh H, Yarali B, Rohani M, Karimi P, Elahi HML, Hosseiny SMM, Sadeghzadeh MS, Mohebbi H, Moghadam MH, Aryan H, Vahidnezhad H, Soveizi M, Rabbani B, Rabbani A, Mahdieh N, Garshasbi M, Tavasoli AR
Neurogenetics 2023 Oct;24(4):279-289. Epub 2023 Aug 19 doi: 10.1007/s10048-023-00730-y. PMID: 37597066
Duignan S, Wright S, Rossor T, Cazabon J, Gilmour K, Ciccarelli O, Wassmer E, Lim M, Hemingway C, Hacohen Y
Dev Med Child Neurol 2018 Sep;60(9):958-962. Epub 2018 Feb 22 doi: 10.1111/dmcn.13703. PMID: 29468668

Diagnosis

Martínez-Rubio D, Hinarejos I, Argente-Escrig H, Marco-Marín C, Lozano MA, Gorría-Redondo N, Lupo V, Martí-Carrera I, Miranda C, Vázquez-López M, García-Pérez A, Marco-Hernández AV, Tomás-Vila M, Aguilera-Albesa S, Espinós C
Int J Mol Sci 2023 Nov 16;24(22) doi: 10.3390/ijms242216400. PMID: 38003592Free PMC Article
Ashrafi M, Kameli R, Hosseinpour S, Razmara E, Zamani Z, Rezaei Z, Mashayekhi R, Pak N, Barzegar M, Azizimalamiri R, Kashani MR, Khosroshahi N, Rasulinezhad M, Heidari M, Amanat M, Abdi A, Mohammadi B, Mohammadi M, Zamani GR, Badv RS, Omrani A, Nikbakht S, Bereshneh AH, Movahedinia M, Moghaddam HF, Ardakani HS, Akbari MG, Tousi MB, Shahi MV, Hosseini F, Amouzadeh MH, Hosseini SA, Nikkhah A, Khajeh A, Alizadeh H, Yarali B, Rohani M, Karimi P, Elahi HML, Hosseiny SMM, Sadeghzadeh MS, Mohebbi H, Moghadam MH, Aryan H, Vahidnezhad H, Soveizi M, Rabbani B, Rabbani A, Mahdieh N, Garshasbi M, Tavasoli AR
Neurogenetics 2023 Oct;24(4):279-289. Epub 2023 Aug 19 doi: 10.1007/s10048-023-00730-y. PMID: 37597066
Duignan S, Wright S, Rossor T, Cazabon J, Gilmour K, Ciccarelli O, Wassmer E, Lim M, Hemingway C, Hacohen Y
Dev Med Child Neurol 2018 Sep;60(9):958-962. Epub 2018 Feb 22 doi: 10.1111/dmcn.13703. PMID: 29468668
Kumar S, Mattan NS, de Vellis J
Ment Retard Dev Disabil Res Rev 2006;12(2):157-65. doi: 10.1002/mrdd.20108. PMID: 16807907

Prognosis

Quental R, Sampaio M, Alonso I, Quental S, Leão M, Sousa R
Neuropediatrics 2023 Apr;54(2):120-125. Epub 2023 Jan 18 doi: 10.1055/s-0042-1760366. PMID: 36652953
Duignan S, Wright S, Rossor T, Cazabon J, Gilmour K, Ciccarelli O, Wassmer E, Lim M, Hemingway C, Hacohen Y
Dev Med Child Neurol 2018 Sep;60(9):958-962. Epub 2018 Feb 22 doi: 10.1111/dmcn.13703. PMID: 29468668

Clinical prediction guides

Quental R, Sampaio M, Alonso I, Quental S, Leão M, Sousa R
Neuropediatrics 2023 Apr;54(2):120-125. Epub 2023 Jan 18 doi: 10.1055/s-0042-1760366. PMID: 36652953

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