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Hypomyelinating Leukodystrophy due to HSPD1 Mutations: A New Patient
Maria Schioldan Kusk1, Bodil Damgaard2, Lotte Risom3
1Department of Pediatrics, Nordsjællands Hospital, Hillerød, Denmark.
Abstract:
The hypomyelinating leukodystrophies (HMLs) encompass the X-linked Pelizaeus-Merzbacher disease (PMD) caused by PLP1 mutations and known as the classical form of HML as well as Pelizaeus-Merzbacher-like disease (PMLD) (Online Mendelian Inheritance in Man [OMIM] 608804 and OMIM 260600) due to GJC2 mutations. In addition, mutations in at least 10 other genes are known to cause HMLs. In 2008, an Israeli family with clinical and neuroimaging findings similar to those found in PMD was reported. The patients were found to have a homozygous missense mutation in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60), and the disorder was defined as the autosomal recessive mitochondrial Hsp60 chaperonopathy (MitCHAP-60) disease. We here report the first case of this severe neurodegenerative disease since it was first described. Given the fact that the families carried the same mutation our patient probably belongs to the same extended family as the Israeli family. In conclusion, the MitCHAP-60 disease should be considered as a rare differential diagnosis in HML.
Insights
Mitochondrial Hsp60 chaperonopathy (MitCHAP-60) disease, a rare neurodegenerative disorder, is caused by HSPD1 mutations. This study reports a new case, highlighting MitCHAP-60 as a crucial differential diagnosis for hypomyelinating leukodystrophies (HMLs).
Area of Science:
- Neurogenetics
- Mitochondrial Biology
- Rare Diseases
Background:
- Hypomyelinating leukodystrophies (HMLs) are a group of rare genetic disorders affecting myelin development.
- Pelizaeus-Merzbacher disease (PMD) and Pelizaeus-Merzbacher-like disease (PMLD) are well-characterized forms of HML.
- Mutations in over 10 genes are known to cause HMLs, underscoring the genetic heterogeneity of these conditions.
Observation:
- A family was previously identified with a homozygous missense mutation in HSPD1, causing autosomal recessive mitochondrial Hsp60 chaperonopathy (MitCHAP-60) disease.
- This study presents the first reported case of MitCHAP-60 disease since its initial description.
- The patient exhibits severe neurodegenerative symptoms and neuroimaging findings consistent with HML.
Findings:
- The patient carries a homozygous missense mutation in HSPD1, confirming the diagnosis of MitCHAP-60 disease.
- Genetic analysis suggests the patient may belong to the same extended family as the previously reported Israeli family.
- This case reinforces the link between HSPD1 mutations and this severe neurodegenerative phenotype.
Implications:
- MitCHAP-60 disease, caused by HSPD1 mutations, should be considered in the differential diagnosis of HML.
- Understanding the genetic basis of HMLs, including rare forms like MitCHAP-60, is crucial for accurate diagnosis and potential therapeutic strategies.
- Further research into mitochondrial chaperonopathies may reveal new insights into neurodevelopmental disorders.
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