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Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter.

ABSTRACT: BACKGROUND: ?/?-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. CASE PRESENTATION: We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5' regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. CONCLUSIONS: This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients.

SUBMITTER: Missaglia S

PROVIDER: S-EPMC3995635 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter.

Missaglia Sara S Valadares Eugenia Ribeiro ER Moro Laura L Faguntes Eleonora Druve Tavares ED Quintão Roque Raquel R Giardina Bruno B Tavian Daniela D

BMC medical genetics 20140314

<h4>Background</h4>α/β-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver st ...[more]

PMID: 24628803

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Project description:BackgroundChanarin-Dorfman syndrome (CDS) is a rare syndromic disease related to an accumulation of triacylglycerol in most organs. The aim of our study was to investigate various organs in a large series of CDS patients.ResultsWe report for the first time thyroid function impairment in CDS. Among 12 investigated patients, 7 showed thyroid function impairment. All of them were over 30 of age. The 5 remaining investigated patients with normal thyroid function were under 30. Thyroid loss of function is an unknown clinical feature of CDS that could gradually develop with age. Thyroid ultrasound showed an abnormal aspect in all investigated patients (6 with thyroid impairment and 3 with normal thyroid function). Cervical MRI done in 2 patients with thyroid impairment showed fat infiltration of thyroid parenchyma. Audiogram carried out in 8 of our patients showed sensorineural hearing impairment in all patients, although only 2 patients suffered from clinical hypoacusia. We also demonstrated that kidney could be a more commonly involved organ than previously reported in the literature. A poorly differentiated kidney parenchyma is a common feature in our series. One patient showed cerebellar atrophy and T2 hypersignal of brain's white matter in MRI. All patients carried the same founder mutation c.773(- 1)G > A in the ABDH5 gene.DiscussionAside from the congenital ichthyosiform erythroderma, the most common symptom of CDS, in addition to other organs involvement frequently reported in the literature, we described thyroid dysfunction, an unreported feature, probably related to the lipid infiltration of the thyroid parenchyma. The association found between age and hypothyroidism in CDS patients could explain the gradually development of thyroid disease with age.ConclusionWe reported a thyroid dysfunction and unreported ultrasonographic aspects of kidneys and cerebral MRI in CDS patients.MethodsWe performed clinical analyses in 15 patients in whom thyroid, liver, ocular, kidney, skeletal muscle and neurological involvement were explored. Genetic and molecular explorations were performed by direct sequence analysis. Software SPSS, Fisher's exact test and ANOVA were used for statistical analyses.

Dataset Information

Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter.

Publications

Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter.

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