A Correlative Synopsis of the Leukodystrophies

Abstract

Leukodystrophies are disorders affecting primarily oligodendroglial cells or myelin. Another necessary criteria for defining a leukodystrophy is that the disorder has to be of endogenous origin with a pattern compatible with genetic transfer of a metabolic defect. The clinical criterion of a steadily progressive deterioration of function must also be included. Much of the material presented during the conference related to three leukodystrophies from which subclasses with a relatively uniform clinical presentation can be distinguished and about which a considerable body of consistent biochemical information is available. These disorders are metachromatic leukodystrophy (MLD), globoid leukodystrophy (GLD, also referred to as Krabbe's disease) and adrenoleukodystrophy (ALD). Discussion was focused to the pathophysiology of the more prevalent "classical" subclass of each of these disorders; discussion of clinical variants was in the context of what we could learn about the more prevalent form. Finally, because of time restraints, most of the discussion on the final day was centered around MLD. This clinical disorder was used as a starting point for discussion of questions both specific to MLD as well as those questions common to all leukodystrophies. The discussion of GLD and ALD was more restricted and only points relevant to those specific leukodystrophies were discussed. Information from the presentation not dealing directly with these human disorders is also summarized.

Animal models of leukodystrophy: a new perspective for the development of therapies

“…The term ‘leukodystrophy’ – first coined in 1928 – has evolved with our growing understanding of these disorders . The first formalised definitions – which considered leukodystrophies primarily as myelin disorders – set the tone for decades of research with a narrow focus on pathogenic mechanisms relating to the myelin sheath and the oligodendrocytes responsible for its formation .…”

Late infantile metachromatic leukodystrophy presenting with extrapyramidal sign

“…This deficiency results in accumulation of the cerebroside sulphate within the myelin sheath of central and peripheral nervous system. This excessive accumulation of the cerebroside sulphate is thought to cause myelin breakdown and damage to oligodendroglial cells [1]. ___________________________________________ *Correspondence: Dr. Sandeep Choudhary, Doctor' Hostel, Room No-208, Dr. Ram Manohar Lohiya Hospital, New Delhi, India.…”

Clinical Pathological Correlation

“…One hypothesis suggests that too much sulfatide is directed to myelin leading to an unstable molecular structure and membrane breakdown [30], Whether demyelination alone accounts for all the clinical symp toms of MLD has not been definitively answered. While it is likely that demyelination accounts for the motor symptoms, it is unclear whether intellectual impairment is due to involvement of shorter myelinated fibers or neuronal damage.…”

“…An electroencephalogram done while patient was awake showed amorphous activity in all leads with little interlcad differentiation with dominant frequency of 5-7 Hz and ampli tude of [30][31][32][33][34][35][36][37][38][39][40] pV. An old-fashioned brain scan was normal.…”