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Prepair 1000+

Gene: HPDL

No list

HPDL (4-hydroxyphenylpyruvate dioxygenase like)
EnsemblGeneIds (GRCh38): ENSG00000186603
EnsemblGeneIds (GRCh37): ENSG00000186603
HPDL is in 11 panels

1 review

Andrew Coventry (Victorian Clinical Genetics Services)

Green List (high evidence)

Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA) is an autosomal recessive disorder characterised by impaired psychomotor development apparent in infancy. Affected individuals show poor overall growth, progressive microcephaly, and axial hypotonia, with later onset of spasticity. Progressive - some patients show normal early development, but later have regression of motor, cognitive, and language skills. More variable features include seizures, joint contractures, ocular disturbances, episodic respiratory failure, and nonspecific dysmorphic facial features. The intellectual impairment is variable, ranging from poor visual contact with inability to walk or speak to milder intellectual disability with the ability to say some words.
Autosomal recessive spastic paraplegia-83 (SPG83) is a neurologic disorder characterized by progressive lower limb spasticity resulting in gait instability. Patients develop symptoms in the second decade, consistent with juvenile onset. Some patients may have myalgia or mild dysarthria, but the phenotype is considered to be a pure type of SPG with no additional neurologic abnormalities.
- Although two distinct distinct disease associations have been assigned by OMIM, these clinical presentations likely represent a continuum of severity for an underlying mitochondrial disorder (Clingen categorised as Leigh syndrome MONDO:0009723).

17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%). Frequently observed clinical findings included chronic progression of neurological signs (n = 16/17, 94%), motor developmental delay (n = 12/17, 71%), intellectual impairment (n = 11/17, 65%), microcephaly (n = 9/16, 56%), and seizures/epilepsy (n = 9/17, 53%). Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%). Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%). Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one.

Functional studies and animal model present.
Created: 6 Mar 2025, 5:11 a.m. | Last Modified: 6 Mar 2025, 5:11 a.m.
Panel Version: 1.1568

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities MIM#619026; Spastic paraplegia 83, autosomal recessive MIM#619027; Leigh syndrome MONDO:0009723

Publications

History Filter Activity

12 Dec 2024, Gel status: 0

Created, Added New Source, Set mode of inheritance

Andrew Coventry (Victorian Clinical Genetics Services)

gene: HPDL was added gene: HPDL was added to Prepair 1000+. Sources: Literature Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal