Leigh's disease in an adult with evidence of “inhibitor factor” in family members

Abstract

A 21-year-old man with a longstanding history of impaired visual acuity, strabismus, broad-based gait, and below-average intellectual capacity developed respiratory difficulties and intermittent generalized weakness at age 19. He subsequently showed signs of massive brainstem dysfunction and died. Postmortem examination demonstrated changes compatible with subacute necrotizing encephalomyelopathy of Leigh involving portions of the diencephalon, midbrain, pons, and medulla as well as portions of the spinal cord and optic nerves. Evaluation of family members for presence of the urinary inhibitor factor for thiamine diphosphate phosphoryl transferase revealed abnormal levels in a brother, a maternal uncle, and the maternal grandfather of the patient.

Chronic leigh disease: A genetic and biochemical study

“…largely considered a familial degenerative neurological disorder of infancy and early childhood that usually has a fatal outcome within two years [17]. In recent years a few adults with SNE have been identified by postmortem examination [6,13,[23][24][25]. In these patients, an acute or subacute illness developed either without antecedent clinical symptoms [6,131 or following longstanding neurological involvement [6,[23][24][25].…”

“…In recent years a few adults with SNE have been identified by postmortem examination [6,13,[23][24][25]. In these patients, an acute or subacute illness developed either without antecedent clinical symptoms [6,131 or following longstanding neurological involvement [6,[23][24][25]. Because of the paucity of data from adult patients, there are no known criteria, except duration of the disease, which can be used to distinguish an "adult form" from a "childhood form" of SNE [23, 251. Although the pathogenesis of the disorder is not yet fully elucidated, a disturbance in thiamine metabolism has been implicated.…”

“…In addition, it has been used to identify some, but not all, obligate carriers [15, 171. Though the assay has been helpful in identifying high-risk families, false positive and false negative results occur [17, 201. We recently reported a patient who died of Leigh disease at 2 1 years of age, and we presented evidence that the TDP-ATP phosphoryltransferase inhibitor factor was present in members of his immediate family [25]. Because the patient came from a small, isolated Greek island with a total population of 1,200, we were presented with the unusual opportunity of investigating an inbred, high-risk population from which Leigh disease in an adult had been documented.…”

Familial subacute necrotizing encephalomyelopathy of the adult form (adult Leigh syndrome)

“…The patient was divorced, and the medical history of her former husband was not available. At the age of 22 years, bilateral optic atrophy had been diagnosed, accompanied by hyperactive tendon reflexes in the lower extremities and a left Babinski sign. Her neurological status had remained more or less the same until the age of 47, when clonic jerks and paresthesias in the left upper extremity and ataxia suddenly appeared.…”

Pyruvate Decarboxylase Deficiency in Subacute Necrotizing Encephalomyelopathy

“…Qubacute necrotizing encephalomyelopathy (SNE) is a recessively inherited disorder of children, charac¬ terized by progressive encephalopa¬ thy, bulbar paresis, abnormal ocular motility, ataxia, and peripheral neu¬ ropathy.1 Subacute necrotizing encephalomyelopathy occurs rarely in old¬ er children and adults. 2 Macroscopic examination of the brain shows char¬ acteristic necrotizing lesions of the deep midline structures, but sparing of the mamillary bodies; microscopi¬ cally the necrotic lesions show demyelination, capillary proliferation, and cell loss. 3 The histologie change resem¬ bles Wernicke's encephalopathy, and hyperpyruvicemia and hyperlactatem¬ ía are present in some patients, hence a disturbance in pyruvate metabolism has been suspected.…”