Mucolipidosis Type IIIA: GNPTAB Gene Deletion/Duplication

Condition Description

Mucolipidosis III A (ML III, pseudo-Hurler polydystrophy) is an autosomal recessive lysosomal storage disorder characterized by short stature, skeletal dysplasia, and mild mental retardation and survival up to adulthood.

Fibroblasts from ML III patients have numerous cytoplasmic inclusion bodies. The accumulation of material in the lysosomes results from the inability of the lysosomal enzymes to enter the lysosome for normal degradation. A biochemical marker signal is required for proper trafficking of the lysosomal enzymes, from the site of production in the endoplasmic reticulum to the lysosome itself. This marker was identified as a mannose-6-phosphate residue on the lysosomal enzyme that interacts with a specific receptor on the lysosomal membrane, which then triggers entry into the lysosome. The biochemical defect in ML III disease is due to the deficiency of the enzyme UDP-N-acetylglucosamine- N-acetylglucosamine- l-phosphotransferase (abbreviated GlcNAc phosphotransferase) involved in the addition of the mannose-6-phosphate residue. The genetic defect causing this disorder results in mislocalization of the lysosomal enzymes such that they are, in part, secreted from the cell rather than transported into the lysosomes. Many lysosomal enzymes have decreased intracellular activities but increased activities in the serum and urine. The electrophoretic patterns of a number of lysosomal enzymes also are altered in ML III fibroblasts. The disorder mucolipidosis II (ML II, I-cell disease) is clinically and biochemically very similar to ML III, although with more severe characteristics leading to death by 6 years of age. Lysosomal enzyme activities also are very low in fibroblasts and have abnormal electrophoretic patterns different from ML III.

Mutations to the GNPTAB gene cause deficiency of this enzyme. Diagnostic sequencing analysis of the GNPTAB gene coding region is available for Mucolipidosis III A patients and their at-risk relatives on a clinical basis.

For questions about testing for ML IIIA, call EGL Genetics at (470) 378-2200 or (855) 831-7447. For further clinical information about lysosomal storage diseases, including management and treatment, call the Emory Lysosomal Storage Disease Center at (404) 778-8565 or (800) 200-1524.

1). Leroy JG, Spranger JW. I-cell disease. N Engl J Med. 1970 Sep 10;283(11):598-9.
2). Kudo M, Brem MS, Canfield WM: Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene. Am. J. Hum. Genet. 78: 451-463, 2006.
3). Olkkonen VM, Ikonen E. Genetic defects of intracellular-membrane transport. New Eng. J. Med. 343: 1095-1104, 2000.
4). Tiede S, Storch S, Lubke T, Henrissat B, Bargal R, Raas-Rothschild A, Braulke T. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Nature Med. 11: 1109-1112, 2005.

Genes (1)

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  • Confirmation of clinical diagnosis of ML IIIA disease
  • Prenatal testing for known familial mutation(s).
  • Assessment of carrier status in high risk family members known mutation analysis.


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (
Submit only 1 of the following specimen types
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside EGL Genetics, please submit a copy of the sequencing report with the test requisition. Contact the laboratory if further information is needed.
  • Known mutation analysis (Custom Diagnostics) is available to test family members.
  • Prenatal testing is available for known familial mutations only. Please call the Laboratory Genetic Counselor for specific requirements for prenatal testing before collecting a fetal sample.

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