Metachromatic Leukodystrophy - Type II (Juvenile Form)
Etiology and Pathogenesis [1,2]One of a group of genetic disorders called the leukodystrophies that affect the growth of the myelin sheath, the fatty covering on nerve fibers in the brain that acts as an insulator. MLD is the result of a failure in the breakdown of sulfatides in the course of normal myelin maintenance and replacement. This is usually the result of a severe deficiency in arylsulfatase A, the first enzyme in the sulfatide degradative pathway. Key Symptom Images Clinical Description and Progression/Prognosis [1,2]Progressive loss of physical and intellectual functions in all forms of the disease. Normal development up to 4-12 years of age. Initial symptoms often relate to a deterioration of intellectual performance and/or behavioral changes, often diagnosed as a variety of psychiatric conditions. The later the age of onset, the slower the rate of progression. Inheritance pattern: autosomal recessive Incidence: 1 in 92,000 live births (for types I, II, and III together) [3] Diagnosis: Enzyme (ASA) deficiency, Saposin B deficiency. Urinary sulfatides. Clinical diagnosis: symptoms and laboratory tests, including brain CT and MRI, nerve conduction velocity [5]. Conditions with similar presentations: Multiple sulfatase deficiency Management:[1] bone marrow transplantation has been used Other medical care: symptom management; drugs may mitigate some symptoms but do not slow disease progression
 Psychomotor retardation Gait disturbances Loss of developmental milestones by end of first decade Ataxia with progressive gait disturbances leading to loss of ambulation Progressive hypertonia with tremor, postural abnormalities, and/or leg scissoring Diminished deep tendon reflexes Slurred speech with speech deterioration Cognitive/behavioral problems: Abnormal/bizarre behavior Difficulty following directions Emotional difficulties Mental deterioration Ocular Optic atrophy leading to blindness Back to categories
1. National Institute of Neurological Disorders and Stroke www.ninds.nih.gov/health_and_medical/disorders/meta_leu_doc.htm. Accessed July 2004. 2. Nyhan WL, Ozand PT. Atlas of Metabolic Diseases. London: Chapman & Hall Medical, 1998; 608-613. 3. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of Lysosomal Storage Disorders. JAMA. 1999; 281: 249-254. 4. National Center for Biotechnology Information; OMIM(TM), Online Mendelian Inheritance in Man. www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=250100 Accessed July 2004. 5. Lyon G, Adams RD, Kolodny EH. Neurology of Hereditary Metabolic Diseases of Children. McGraw-Hill, 2nd edition. 1996; 244-245 |
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