Advance of research on Hereditary spastic paraplegia type 4 / 中华医学遗传学杂志

Spastic paraplegia type 4 (SPG4) is the most common type of autosomally inherited spastic paraplegia. Its main clinical features include typical simple hereditary spastic paraplegia, with neurological impairments limited to lower limb spasticity, hypertonic bladder dysfunction, and mild weakening of lower limb vibration sensation, without accompanying features such as nerve atrophy, ataxia, cognitive impairment, seizures, and muscle tone disorders. SPAST is the main pathogenic gene underlying SPG4, and various pathogenic SPAST variants have been discovered. This disease has featured a high degree of clinical heterogeneity, and the same pathogenic variant can have different age of onset and severity among different patients and even within the same family. There is a lack of systematic research on the correlation between the genotype and phenotype of SPG4, and the pathogenic mechanism has remained controversial. This article has provided a review for the clinical characteristics, pathogenic gene characteristics, correlation between the genotype and phenotype, and pathogenic mechanism of this disease, with an aim to provide reference for its clinical diagnosis and treatment.

Identification of SPAST gene variant in a pedigree affected with hereditary spastic paraplegia type 4 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4).@*METHODS@#Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing.@*RESULTS@#DNA sequencing suggested that the proband has carried a heterozygous c.1196C>G variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic.@*CONCLUSION@#The c.1196C>G variant of the SPAST gene probably underlay the HSP4 in this pedigree.

Paraplejia espástica e insuficiencia suprarrenal primaria: un caso de adrenomieloneuropatia / Spastic paraplegia and primary adrenal insuficiency: a case of adrenomyeloneuropathy

Un varón de 40 años se internó por dificultad creciente para la marcha que había comenzado 2 años antes y que lo había reducido a una silla o a la cama. Hacía 7 años se le había diagnosticado enfermedad de Addison y tomaba regularmente 20 mg/día de hidrocortisona oral. Su padre, un tío paterno y 2 hermanas están sanos; un hermano afectado por oligofrenia, disartria y dificultad para caminar falleció a los 9 años de edad. A su ingreso, el paciente estaba lúcido y orientado,; tenía hiperpigmentaciín leve de piel y mucosas, alopecía en cuero cabeludo y cola de cejas, testículos de 3,5 ml y paraplejía espástica; los miembros inferiores conservaban la sensibilidad táctil y dolorosa. La radiografía de tórax y la reacción de Mantoux eran normales. Las pruebas hormonales de laboratorio confirmaron la insuficiencia suprarrenal primaria (con conservación de la función de la zona glomerulosa) y un hipogonadismo primario; la función tiroidea era normal. La velocidad de conducción motora en miembros inferiores era baja (30-32 m/seg), con aumento de las latencias proximal y distal; esto y el EMG eran compatibles con polineuropatía de tipo mielinopático. Se comprobó leve atrofia cortical difusa (TAC) de cráneo); los potenciales evocados auditivos de tronco cerebral mostraron baja amplitud del complejo IV-V y tiempo de conducción central prolongado (5,3 mseg). Los ácidos grasos séricos eran cuantitativa y cualitativamente normales por cromatografía gaseosa. En la biopsia de nervio safeno se observó desmielinización segmentaria y degeneración axonal, sin infiltrados inflamatorios; el estudio ultraestructural demostró, en el citoplasma de algunas células de Schwann, inclusiones bilaminares, en su mayoría curvalíneas, que confirmaron el diagnósticos clínico de adrenomieloneuropatía. Esta rara enfermedad familiar de transmisión recesiva ligada al cromosoma X se origina en un trastorno del metabolismo de los ácidos grasos saturados de cadena muy larga, con compromiso funcional del sistema nervioso y de células productoras de hormonas esteroides

Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) is a rare hereditary disorder and becomes clinically apparent during adolescence or in childhood and progresses s1owly throughout the adult years with a variability in the severity of expression. We experienced 3 cases of hereditary spastic paraplegia. Cases 1 and 2, which were pure HSP, had only the signs and symptoms of corticospinal tract involvement with the positive family history, and case 3, which was a complicated case of HSP, had distal muscle wasting, dysarthria, signs and symptoms of the corticospinal tracts, and a positive family history. All are thought to be inherited in an autosomal dominant pattern.