Hereditary spastic paraplegia (SPG 48) with deafness and azoospermia: A case report.

Hereditary spastic paraplegias (HSP) are inherited neurodegenerative disorders characterized by progressive paraplegia and spasticity in the lower limbs. SPG48 represents a rare genotype characterized by mutations in AP5Z1, a gene playing a role in intracellular membrane trafficking. This study describes a case of a 53-year-old male patient with SPG48 presenting spastic paraplegia, infertility, hearing impairment, cognitive abnormalities and peripheral neuropathy. The Sanger sequencing revealed a homozygous deletion in the chr 7:4785904-4786677 region causing a premature stop codon in exon 10. The patient's brother was heterozygous for the mutation. The brain magnetic resonance imaging found a mild brain atrophy and white matter lesions. In the analysis of the auditory thresholds, we found a significant hearing decrease in both ears.

Polyglucosan body myopathy 1 may cause cognitive impairment: a case report from China.

BACKGROUND: Polyglucosan body myopathy 1 (PGBM1) is a type of glycogen storage disease that can cause skeletal muscle myopathy and cardiomyopathy with or without immunodeficiency due to a pathogenic mutation in the RBCK1 gene. PGBM1 has been reported in only 14 European and American families, and no cognitive impairment phenotype was reported. Its prevalence in Asia is unknown. CASE PRESENTATION: We report a Chinese boy with teenage onset of skeletal muscle myopathy and mild cognitive impairment. Whole-exome sequencing analysis identified a homozygous missense mutation in RBCK1 (c.1411G > A:p.Glu471Lys). A muscle biopsy indicated the accumulation of periodic acid-Schiff-positive material, which could be ubiquitinated by immunohistochemistry with an anti-ubiquitin antibody. In skeletal muscle tissue, HOIL-1 and HOIP protein levels were lower than those in the control, confirming the phenotype of an RBCK1 mutation. MRI revealed abnormal cerebral white matter signals. Immune system and cardiac examination found no abnormalities. The patient was diagnosed with PGBM1 with no effective treatment. CONCLUSIONS: This case from China with a novel homozygous missense mutation in RBCK1 extends the phenotypic spectrum and geographical distribution of PGBM 1, which may cause cerebral white matter changes and cognitive impairment.

[Analysis of a cerebrotendinous xanthomatosis case with mental retardation as the initial symptom].

OBJECTIVE: To analyze a case of cerebrotendinous xanthomatosis (CTX) with mental retardation as the initial neurological symptom. METHODS: Medical imaging, histopathological assay and genetic testing were carried out to analyze the patient. RESULTS: Neurological manifestations of the 27-year-old male patient were initiated by mental retardation and subsequently memory lapses, ataxia, spastic paraplegia and fuzzy language. Other symptoms included cataract, xanthomatosis in Achilles tendon, kidney stones and high arches. The total bile acid in serum has risen to 14.7 umol/L. There were symmetrical abnormal signals in bilateral cerebellar dentate nuclei, hypointensities on T1WI and DWI and mixed signals on T2WI. Cholesterol crystallization and cholesterol granulomatous inflammation were found upon pathological examination of the Achilles tendon. The patient was found to have carried a compound heterozygous mutation of the CTX gene, which consisted of two novel mutations including c.379C>T (p.Arg127Trp) in exon 2 and c.1174G>A (p.Glu392Lys) in exon 6 of the CYP27A1 gene. CONCLUSION: Clinicians should be alert to cerebrotendinous xanthomatosis when the patient has mental retardation caused by genetic and metabolic factors beginning at a young age, particularly accompanied with tendinous xanthomatosis and cataracts. CTX can be readily diagnosed by histopathological assay and sequencing of the CYP27A1 gene.