Contribution to clinical characterization of autosomal recessive hereditary ataxias

THESES

Contribution to clinical characterization of autosomal recessive hereditary ataxias (Abstract)^*. Theses. São Paulo, 2009

Emília Katiane Embiruçu^**

Autosomal recessive hereditary ataxias belong to a group of heterogeneous disorders, for which detailed clinical evaluation, ancillary exams, and sometimes, genetic tests, are required for diagnosis. After literature review, an algorithm was built to help the investigation of this group. The objective of this thesis is to present the results of investigation of three forms of recessive ataxias: [1] Joubert syndrome is a condition characterized by early hypotonia, developmental delay, ataxia and neonatal respiratory disturbances or abnormal eye movement. It has a wide clinical spectrum and is a genetically heterogeneous. Renal, hepatic and retina abnormalities are often seen. A combination of midline cerebellar vermis hypoplasia, deepened interpeduncular fossa, and thick, elongated superior cerebellar penduncles gives to the axial view of the midbrain an appearance of a molar tooth at brain magnetic resonance image (MRI) study. Molar tooth sign is considered as obligatory radiologic criteria to diagnosis. In this study we present a series of five patients that have clinical and radiologic criteria to Joubert syndrome and a large phenotypic variability: two children have a pure form (subgroup 1), one child has an associated retinopathy (subgroup 2), the other has Leber congenital amaurosis and kidney abnormalities (subgroup 4), and another has chorioretinal coloboma and hepatic abnormalities (subgroup 5); [2] Ataxia with vitamin E deficiency, which has a phenotype similar to Friedreich ataxia but slowest progression, is characterized by low levels of serum α-tocopherol and is treatable with vitamin E. This ataxia is common in South Italy and North Africa, but was not reported in Brazil. Four patients from two different families were studied. Three of them have typical clinical features and hands dystonia, a probably underreported feature which might helps its distinction from Friedreich ataxia. The other case was identified in a pre-symptomatic stage, after family investigation. After five years of treatment with vitamin E, subtle balance disturbance was still present. The reaming three patients improved with vitamin E supplementation and disease progression stopped; [3] Cerebrotendinous xanthomatosis (CTX) is a disorder of cholesterol metabolism, characterized by reduction of bile acid synthesis and accumulation of cholestanol, a toxic metabolic. Congenital or juvenile cataract and chronic diarrhea are early manifestations. Cerebellar ataxia, spastic paraplegia, cognitive impairment and tendinous xanthomatosis are also seen. Brain MRI T2-weghted and FLAIR sequences disclosed dentate nucleus hypersignal, a quite feature in CTX. Three patients from two different families, with clinical and radiologic features were studied. In all, serum cholestanol was elevated. MRI spectroscopy demonstrated in cerebellum a peak in 1.2-1.4 ppm, which is a possibly a lipid, not previously described. Treatment with chenodeoxycholic acid improved their gait.

*

Contribuição para a caracterização clínica das ataxias hereditárias autossômicas recessivas (Resumo). Tese de Doutorado. Universidade de São Paulo, USP (Área: Neurologia). Orientador: Fernando Kok.

Publication Dates

• Publication in this collection
  01 Sept 2011
• Date of issue
  Aug 2011