I cell disease (MLll/lll αβ)

Introduction

I-cell disease (also called mucolipidosis II/lll αβ, MLII/lllαβ) is an autosomal recessive disorder caused by a deficiency of the membrane bound enzyme UDP-N –acetylglucosamine- 1-phosphotransferase. The GNPTAB gene encodes two out of three subunits of this enzyme; a heterohexameric complex of two alpha, two beta, and two gamma subunits. The encoded protein is proteolytically cleaved to yield mature alpha and beta polypeptides while the gamma subunits are the product of a distinct gene (GNPTG). Mutations in the GNPTAB gene prevents appropriate trafficking of lysosomal enzymes and thus prevent normal processing. One unique feature of this disease is the presence of phase-dense intracytoplasmic inclusions in the fibroblasts of patients. These cells are termed inclusion cells, or I-cells, thus, the disease is designated I-cell disease. Individuals with more severe features have ML IIαβ; those with less severe, or attenuated, features have ML IIIαβ. I-cell disease is characterized by severe psychomotor retardation that rapidly progresses leading to death between 5 and 8 years of age. Although there are similar signs and symptoms, the earlier onset of symptoms and the lack of mucopolysacchariduria distinguish I-cell disease from Hurler syndrome (MPSl). The GNPTAB gene is located on chromosome 12q23.3.

Referral information

This service is funded by the National Commissioning Group (NCG). Samples received from England, Northern Ireland and Scotland are charged to NCG with the majority of samples being received from The Willink Metabolic Unit. New patients are initially diagnosed by enzyme analysis, therefore patients will usually have already been referred to a relevant NCG centre before DNA analysis is requested. Funding from the NCG also covers carrier detection, by DNA analysis, for family members.

Price & reporting times

Test Price NHS (£) Price non- NHS (£ ) TRT (calendar days)
Mutation scanning POA POA 56
Single mutation test POA POA 28
Urgent/Predictive single mutation test POA POA 14

Test validation & quality assurance - information for users

The laboratory is UKAS assessed against ISO 15189 standards.

Sample requirements

4ml EDTA blood sample

Referral guidelines

Please see our referral guidelines for more information.

OMIM Number(s) - 252500

Gene(s) - GNPTAB

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