1043-3155 Pediatr Neurol Briefs pedneurbriefs Pediatr Neurol Briefs Pediatric Neurology Briefs Pediatr Neurol Briefs 2166-6482 1043-3155 2166-3155 Pediatric Neurology Briefs Publishers Chicago, IL, USA PNB-7-62-b 10.15844/pedneurbriefs-7-8-8 Degenerative Diseases Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Metachromatic Leukodystrophy Variants http://orcid.org/0000-0002-0173-7931 Millichap J. Gordon MD 1 2 * Division of Neurology, Children's Memorial Hospital, Chicago, IL Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL Correspondence: Dr. J. Gordon Millichap, E-mail: jgmillichap@northwestern.edu 08 1993 01 07 2016 7 8 62 63 Copyright: © 1993 The Author(s) 1993 This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Metachromatic leukodystrophy: multiple nonfunctional and pseudodeficiency alleles in a pedigree: problems with diagnosis and counseling

Clinical, pathological, imaging, and genetic findings in a family with multiple allelic mutations of metachromatic leukodystrophy (MLD) are reported from McGill University, Montreal, and McMaster University, Hamilton, Canada.

 Metachromatic Leukodystrophy Pseudodeficiency Allelic Mutations

Clinical, pathological, imaging, and genetic findings in a family with multiple allelic mutations of metachromatic leukodystrophy (MLD) are reported from McGill University, Montreal, and McMaster University, Hamilton, Canada. The propositus, a 23-year-old man, presented at age 18 with a 3-year history of clumsiness and stiffness of gait. Two maternal uncles, ages 48 and 56, were also neurologically impaired. Two siblings, a brother aged 30 and sister aged 25, the mother, and father were clinically normal and had normal electrical studies and MRIs, but their arylsulfatase activity was reduced. Allele-specific amplification confirmed the pseudodeficiency (PD) allele, with no clinical dysfunction, in the mother and her 2 unaffected children. The mother was a PD/MLD compound heterozygote since she was an obligate MLD carrier. The father was a normal (N/MLD) heterozygote. The family was unique in the unusual occurrence of MLD in consecutive generations in the absence of consanguinity. [1]

COMMENT. Three phenotypes of MLD are recognized based on age of onset: late infantile (0-2 years), juvenile (3-16 years), and adult. The time of onset is determined by the amount of residual arylsulfatase A activity, those retaining some activity having a delayed onset of the disease. A variety of allelic mutations has been identified, including a pseudodeficiency allele with no clinical dysfunction. Cloning of the enzyme gene and genotype identification at the molecular level for the PD and MLD mutations allow appropriate genetic counselling for the families. With these advances in diagnosis, the authors conclude that unnecessary testing of spouses and prenatal screening of pregnancies can be avoided.

 Francis GS Bonni A Shen N Hechtman P Yamut B Carpenter S Metachromatic leukodystrophy: multiple nonfunctional and pseudodeficiency alleles in a pedigree: problems with diagnosis and counseling Ann Neurol 1993 Aug 34 2 212 218 10.1002/ana.410340218 8101704