Hydroxysteroid 17-Beta Dehydrogenase Type 10 Disease in Siblings

Area of Science:

• Genetics and Molecular Biology
• Neuroscience
• Rare Diseases

Background:

• Hydroxysteroid 17-beta dehydrogenase type 10 (HSD10) deficiency (HSD10 disease) is a rare X-linked neurodegenerative disorder.
• Mutations in the HSD17B10 gene cause HSD10 disease, with only 10 mutations reported since 2000.
• Phenotypes range from severe infantile forms to attenuated forms with variable regression.

Purpose of the Study:

• To report the second case of the c.194T>C (p.V65A) mutation in HSD10 disease.
• To describe the clinical features of two half-brothers with this mutation.
• To review and compare reported phenotypes and discuss potential pathophysiology.

Main Methods:

• Clinical case report of two affected half-brothers.
• Review of existing literature on HSD10 disease mutations and phenotypes.
• Analysis of clinical features including neurodevelopmental delay, choreoathetosis, visual loss, cardiac findings, and behavioral abnormalities.

Main Results:

• Two half-brothers presented with a less fulminant phenotype of HSD10 disease associated with the c.194T>C (p.V65A) mutation.
• Clinical features included neurodevelopmental delay, choreoathetosis, visual loss, cardiac findings, and behavioral abnormalities, with noted regression in the older sibling.
• Newborn screening via tandem mass spectroscopy was normal; diagnosis required a high index of suspicion due to atypical organic acid patterns.

Conclusions:

• The V65A mutation in HSD10 disease can present with a variable, less severe phenotype.
• Diagnosis of HSD10 disease necessitates a high index of suspicion, as biochemical markers may be absent or atypical.
• Further research is needed to elucidate the exact pathogenic mechanisms, potentially involving non-dehydrogenase functions of the HSD10 protein.