Mitochondrial neurogastrointestinal encephalomyopathy mimicking chronic inflammatory demyelinating polyradiculoneuropathy

Encefalomiopatia neurogastrointestinal mitocondrial mimetizando polirradiculoneuropatia inflamatória desmielinizante crônica

Camila Pupe; Osvaldo J. M. Nascimento; Giseli Quintanilha; Marcos R. G. de Freitas; Eduardo Uchôa; André P. C. Matta; João Gabriel Dib; Tânia Escada

Departamento de Neurologia e Núcleo de Pesquisa Clínica em Neurologia/Neurociências da Universidade Federal Fluminense (NeuroUPC-UFF), Rio de Janeiro, Brazil

^{Correspondence} Correspondence: Osvaldo J. M. Nascimento Rua Siqueira Campos 53/1204 22031-070 Rio de Janeiro RJ - Brasil Email: osvaldo_nascimento@hotmail.com

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare multisystemic autosomal recessive disease caused by mutations in the gene encoding thymidine phosphorylase¹. The deficiency of this enzyme produces plasma accumulations of its substrates, thymidine and deoxyuridine, that have toxic effect on mitochondrial DNA, leading to multiple deletions and depletion. Clinically, the disease is characterized by severe gastrointestinal dysmotility, cachexia, progressive external ophtalmoplegia, peripheral neuropathy and diffuse leukoencephalopathy on brain magnetic resonance imaging. The diagnosis is made by biochemical and molecular tests². New therapeutic approaches remain unproven.

Case report

A 36-year-old male patient was referred to our hospital presenting general weakness, muscular atrophy, growth and developmental delay since 6 years old. He also had chronic diarrhea associated to abdominal pain, weight loss, nausea and vomiting³.

Cachexia, main muscular groups atrophy and mild palpebral ptosis, associated to ophtalmoparesis were observed. There was symmetrical paresis of both distal and proximal, mainly on the lower limbs and universal areflexia. The sensitive examination revealed distal tactile, thermal and pinprick hypoesthesia.

The electroneuromyography demonstrated demyelinating sensory and motor polyneuropathy, characterized by conduction slowing and increase latency in motor and sensory nerves and conduction block in 2 motor nerves (Table).

Biochemical tests revealed no thymidine phosphorylase activity and significant increase of serum thymidine and deoxyuridine 9.6 e 8.6 mmol/L, respectively; normal <0.05 mmol/L³.

The magnetic resonance imaging (MRI) of the brain showed diffuse leukoencephalopathy affecting both cerebral hemispheres, brain stem and cerebellum.

The muscular biopsy revealed type 2 fibers atrophy and irregular muscle fibers in size and shape. At electronic microscopy, intense mitochondrial proliferation and modest glycogen accumulation were observed³.

The superficial fibular nerve biopsy revealed demyelinating pattern with thin myelin to the axonal caliber in different remyelinating stages.

The genetic molecular study detected multiple deletions on mitochondrial DNA. No depletions were identified. Homozigotic mutation was found on exon 10 (C4202A) of the ECGF1 gene³.

Discussion

There were described less than 100 cases of MNGIE over the world on the literature¹. Despite being clinically recognizable and a homogeneous disease, its presentation form may vary and exhibit atypical phenotypes¹.

Because it is a rare and recently described disease, many patients are misdiagnosed as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP) and intestinal inflammatory disease⁴. The peripheral neuropathy presented by the patient fulfills the current clinical, electrophysiological and histopathological criteria for CIDP⁵.

In 2004, there were described 5 cases of neuropathy simulating CIDP in patients with MNGIE⁴. Similarities and differences between these two conditions were highlighted. In MNGIE polyneuropathy, proximal weakness is less common than CIDP. Furthermore, there are many other systemic symptoms associated to this disease. Among the studied cases, none of them obtained clinical improvement with immunomodulating therapy⁴.

The diagnosis of MNGIE was finally confirmed with biochemical analysis demonstrating absence of thymidine phosphorylase activity and serum raise of thymidine and deoxyuridine, in addition to identification of the ECGF1 gene mutation on nuclear DNA and multiple deletions on mitochondrial DNA³.

Conflict of interest:

There is no conflict of interest to declare.

Received 08 September 2011

Received in final form 14 October 2011

Accepted 21 October 2011

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