Metachromatic Leukodystrophy

Alternative Names

  • MLD
  • Metachromatic Leukoencephalopathy
  • Cerebral Sclerosis, Diffuse, Metachromatic Form
  • Sulfatide Lipidosis
  • Arylsulfatase A Deficiency
  • ARSA Deficiency
  • Cerebroside Sulfatase Deficiency
  • Pseudoarylsulfatase A Deficiency
  • Metachromatic Leukodystrophy, Late Infantile
  • Metachromatic Leukodystrophy, Juvenile
  • Metachromatic Leukodystrophy, Adult

Associated Genes

Arylsulfatase A
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number

250100

Mode of Inheritance

Autosomal recessive

Gene Map Locus

22q13.33

Description

Metachromatic Leukodystrophy (MLD) is an autosomal recessive leukodystrophy, characterized by a buildup of sulfatide fat in cells, especially in cells of the nervous system. The sulfatide accumulation stains differently and appears in the form of metachromatic granules under the microscope. The accumulation causes progressive destruction of the myelin sheath, leading to characteristic signs and symptoms. It is estimated that MLD occurs in every one in about 40,000 individuals worldwide. However, some populations, including some Arab groups in Palestine and a group of Jews who migrated from Southern Arabia (Habbanites) have been shown to have much higher frequencies of the disease.

Molecular Genetics

Mutations in the ARSA gene, which codes for the lysosomal Arylsulfatase A enzyme, are the most common cause of MLD. Arylsulfatase A is one of the enzymes playing major roles in the metabolism of sphingolipids, which form a part of the myelin sheath. 

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
250100.1Lebanon Metachromatic leukodystrophy variant; ...NM_001085427.2:c.470C>GHomozygousAutosomal, RecessiveGieselmann et al. 1994
250100.2.1LebanonYesYes Global developmental delay; Behavioral a...NM_001085427.2:c.827C>THomozygousAutosomal, RecessiveHarvey et al. 1993 Sister of 250100.2.2...
250100.2.2LebanonFemaleYesYes Global developmental delay; Behavioral a...NM_001085427.2:c.827C>THomozygousAutosomal, RecessiveHarvey et al. 1993
250100.2.3LebanonFemaleYesYes Global developmental delay; Behavioral a...NM_001085427.2:c.827C>THomozygousAutosomal, RecessiveHarvey et al. 1993
250100.3LebanonMaleNoYes Difficulty walking; Poor fine motor coor...NM_001085427.2:c.827C>THomozygousAutosomal, RecessiveHarvey et al. 1993
250100.4.1LebanonMaleNoYes Clumsiness; Spastic gait; Motor delay; D...NM_001085427.2:c.827C>THomozygousAutosomal, RecessiveHarvey et al. 1993
250100.4.2LebanonMaleNoYes Muscle weakness; AreflexiaNM_001085427.2:c.827C>THomozygousAutosomal, RecessiveHarvey et al. 1993
250100.5PalestineOthersYes Motor deteriorationNM_001085427.2:c.465+1G>AHomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.6PalestineOthersYes Motor deteriorationNM_001085427.2:c.465+1G>AHomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.7PalestineOthersYes Motor deteriorationNM_001085427.2:c.465+1G>AHomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.8.1PalestineOthersYesNM_001085427.2:c.827C>THomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.9.1PalestineOthersYes Motor deteriorationNM_001085427.2:c.1114C>THomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.10.1PalestineYes Motor deteriorationNM_001085427.2:c.292_293delTCinsCTHomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.11.1PalestineYes Motor deteriorationNM_001085427.2:c.576G>CHomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.12.1PalestineYes Motor deteriorationNM_001085427.2:c.263G>AHomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.13PalestineOthersYes Motor deteriorationNM_001085427.2:c.827C>THomozygousAutosomal, RecessiveHeinisch et al. 1995
250100.15Saudi ArabiaOthers Metachromatic leukodystrophy variantNM_001085427.2:c.890C>AHomozygousAutosomal, RecessiveBarth et al. 1993
250100.16LebanonFemale Nystagmus; Hypotonia; Hyperreflexia; ...NM_001085427.2:c.827C>THomozygousAutosomal, RecessiveNair et al. 2018
250100.17LebanonFemaleYes Intellectual disability; Hypotonia; De...NM_000487.6:c.433C>GAutosomal, RecessiveNair et al. 2018

Other Reports

Kuwait

El Khateeb et al. (1988) studied auditory brain stem responses in 35 children with neurologiocal disorders. Five of these patients demonstrated characteristics of metachromatic leukodystrophy.

Oman

Koul et al. (1994) reported two siblings with first degree consanguineous parents diagnosed with metachromatic leucodystrophy.

A hospital register based study by Rajab et al. (2005)  in Oman from 1993 to 2002 revealed that Metachromatic Leukodystrophy was diagnosed in 18 patients, with an observed incidence of 1 in 25,000 births.

Yemen

A study by Schaap et al. (1981) described a pseudodeficiency allele at the arylsulfatase A locus rendering asymptomatic persons with levels of arylsulfatase A that are within the range usually found in metachromatic leukodystrophy (MLD) patients. The subject of this study is a population from Habban (Arabian Peninsula, Southwest of Hadhramaut), an area with high frequency of MLD. 

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