Compound heterozygous mutations in the neuraminidase 1 gene in type 1 sialidosis: A case report and review of literature

BACKGROUND Type 1 sialidosis,also known as cherry-red spot-myoclonus syndrome,is a rare autosomal recessive lysosomal storage disorder presenting in the second decade of life.The most common symptoms are myoclonus,ataxia and seizure.It is rarely encountered in the Chinese mainland.CASE SUMMARY A 22-year-old male presented with complaints of progressive myoclonus,ataxia and slurred speech,without visual symptoms;the presenting symptoms began at the age of 15-year-old.Whole exome sequencing revealed two pathogenic heterozygous missense variants[c.239C>T(p.P80L)and c.544A>G(p.S182G)in the neuraminidase 1(NEU1)gene],both of which have been identified previously in Asian patients with type 1 sialidosis.All three patients identified in China's Mainland come from three unrelated families,but all three show the NEU1 mutations p.S182G and p.P80L pathogenic variants.Increasing sialidase activity through chaperones is a promising therapeutic target in sialidosis.CONCLUSION Through retrospective analysis and summarizing the clinical and genetic characteristics of type 1 sialidosis,we hope to raise awareness of lysosomal storage disorders among clinicians and minimize the delay in diagnosis.

Chinese patient with cerebrotendinous xanthomatosis confirmed by genetic testing: A case report and literature review

BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a treatable autosomal recessive inherited metabolic disorder.It results from a deficiency of sterol 27-hydroxylase(CYP27A1),which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis.Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain,eyes,tendons,and vessels,resulting in juvenile cataracts,tendon xanthoma,chronic diarrhea,cognitive impairment,ataxia,spastic paraplegia,and peripheral neuropathy.CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports.CASE SUMMARY A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied.The patient is a 47-year-old male,who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts,cerebellar ataxia,pyramidal signs and chronic diarrhea.There was a significant increase in the concentration of free fatty acid compared to normal range.Doppler ultrasound of the urinary system showed multiple left kidney stones,a right kidney cyst,and a hypoechoic area in the bladder,which could move with body position.Sagittal and axial magnetic resonance imaging(MRI)of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon,abnormal thickening of the plantar fat,and a small amount of exudation around the fascia in front of the Achilles tendon.Cerebral MRI suggested white matter(WM)demyelination and slight cerebral atrophy.The diagnosis was confirmed by targeted sequencing,which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene(c.435G>T,c.1263+1G>A).Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid.Sediments in the bladder disappeared after therapy.CONCLUSION CYP27A1 genetic analysis should be the definitive method for CTX diagnosis.This case suggests that urinary system diseases may be neglected in CTX patients.The clinical,biological,radiological,and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.