A case of multiple carboxylase deficiency presenting with skin lesions as the initial symptom induced by a novel mutation in the holocarboxylase synthetase gene

2019 ◽  
Keyword(s):  
Novel Mutation ◽  
Skin Lesions ◽  
Initial Symptom ◽  
Holocarboxylase Synthetase ◽  
Multiple Carboxylase Deficiency

scholarly journals Paradoxical Regulation of Biotin Utilization in Brain and Liver and Implications for Inherited Multiple Carboxylase Deficiency

2004 ◽  
Vol 279 (50) ◽  
pp. 52312-52318 ◽  
Author(s):  
Diana Pacheco-Alvarez ◽  
R. Sergio Solórzano-Vargas ◽  
Roy A. Gravel ◽  
Rafael Cervantes-Roldán ◽  
Antonio Velázquez ◽  
...  
Keyword(s):  
High Dose ◽  
Mrna Levels ◽  
Holocarboxylase Synthetase ◽  
Biotin Deficiency ◽  
Multiple Carboxylase Deficiency ◽  
Regulatory Impact ◽  
Normal Metabolism ◽  
Liver And Kidney ◽  
Essential Function ◽  
The Brain

Holocarboxylase synthetase (HCS) catalyzes the biotinylation of five carboxylases in human cells, and mutations of HCS cause multiple carboxylase deficiency (MCD). Although HCS also participates in the regulation of its own mRNA levels, the relevance of this mechanism to normal metabolism or to the MCD phenotype is not known. In this study, we show that mRNA levels of enzymes involved in biotin utilization, including HCS, are down-regulated during biotin deficiency in liver while remaining constitutively expressed in brain. We propose that this mechanism of regulation is aimed at sparing the essential function of biotin in the brain at the expense of organs such as liver and kidney during biotin deprivation. In MCD, it is possible that some of the manifestations of the disease may be associated with down-regulation of biotin utilization in liver because of the impaired activity of HCS and that high dose biotin therapy may in part be important to overcoming the adverse regulatory impact in such organs.

scholarly journals A novel mutation of ABHD5 gene in a Chanarin Dorfman patient with unusual dermatological findings

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ali Haydar Eskiocak ◽  
Sara Missaglia ◽  
Laura Moro ◽  
Murat Durdu ◽  
Daniela Tavian
Keyword(s):  
Neutral Lipids ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Skin Lesions ◽  
Clinical Feature ◽  
Nonalcoholic Fatty Liver ◽  
Pityriasis Rubra Pilaris ◽  
Long Time ◽  
History Of

Abstract Background Chanarin Dorfman Syndrome (CDS) is a rare autosomal recessive disorder characterized by the multisytemic accumulation of neutral lipids inside the cytoplasmic lipid droplets. This condition is caused by mutations in the abhydrolase domain containing 5 gene (ABHD5). In CDS the skin involvement is the prevalent and always observed clinical feature, consisting of a non-bullous congenital ichthyosiform erythroderma (NCIE). Moreover, a variable involvement of the liver and neuromuscular system can be also observed. In this report, we aimed to perform the clinical and genetic characterization of a patient affected by CDS with atypical dermatological findings, considering this rare inborn error of neutral lipid metabolism. Methods Genomic DNA samples obtained from patient and his parents were used to perform the sequencing of the ABHD5 exons and their intron/exon boundaries. Bioinformatic analyses were performed to investigate the possible effect of the identified mutation on protein structure. Results Here we present the case of a 29-year-old male patient with CDS, who, for long time, has been misdiagnosed as pityriasis rubra pilaris (PRP). He has a history of increasing hyperlipidemia; hepatomegaly associated with hepatosteatosis was also detected. ABHD5 molecular analysis revealed a novel missense mutation, the c.811G > A (p.G271R). Bioinformatic investigations showed that the variant has a deleterious effect on ABHD5 function, probably causing an incorrect folding of the mutant protein. Conclusions These results highlihts the importance of genetic testing for ABHD5 in unresolved cases of patients presenting unusual skin lesions, that resemble PRP, associated with a history of hyperlipidemia and nonalcoholic fatty liver.

Widespread central nervous system cavernous malformations associated with café-au-lait skin lesions

2003 ◽  
Vol 99 (2) ◽  
pp. 412-415 ◽  
Author(s):  
Kiran Musunuru ◽  
Virany Huynh Hillard ◽  
Raj Murali
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Novel Mutation ◽  
Skin Lesions ◽  
Neurological Deficits ◽  
Intramedullary Spinal Cord ◽  
Cavernous Malformations ◽  
Content Type ◽  
Brain And Spinal Cord

✓ The simultaneous presence of cavernous malformations in the brain and spinal cord is a very rare finding and is typically associated with familial cavernous malformations. Although they are uncommon, various skin lesions can manifest in patients with familial cavernous malformations. The authors report on a 60-year-old man in whom more than 100 lesions consistent in appearance with cavernous malformations, including several intramedullary spinal cord lesions, were found throughout the neuraxis. This patient also displayed prominent café-au-lait skin lesions, but had no additional signs of neurofibromatosis or other neurocutaneous disorders. Analysis of his DNA revealed a novel mutation in the KRIT1/CCM1 gene, thereby confirming the diagnosis of familial cavernous malformation. The presence of these lesions in every major compartment of this patient's central nervous system underscores their indiscriminate nature and the need to screen throughout the neuraxis in patients in whom familial cavernous malformations are suspected. The findings in this case add to the growing list of skin lesions associated with genetically confirmed familial cavernous malformations. In patients presenting with seizures, focal neurological deficits, or hemorrhagic stroke, the presence of unusual skin lesions should prompt consideration of familial cavernous malformations, and appropriate screening should be performed.

scholarly journals Interferon-induced sarcoidosis with uveitis as the initial symptom: a case report and review of the literature

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ai Kato ◽  
Mami Ishihara ◽  
Nobuhisa Mizuki
Keyword(s):  
Case Reports ◽  
Relevant Literature ◽  
Corticosteroid Treatment ◽  
Pegylated Interferon ◽  
Skin Lesions ◽  
Japanese Woman ◽  
Interferon Α ◽  
Initial Symptom ◽  
Initial Symptoms ◽  
Old Japanese

Abstract Background In recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as initial symptoms. Herein, we describe a rare case of interferon-α-induced sarcoidosis with uveitis as the initial symptom, and present a review of the relevant literature. Case presentation This case involved a 62-year-old-Japanese woman with a history of a combination treatment of pegylated interferon-α-2a, ribavirin, and simeprevir, after which she developed granulomatous panuveitis. She was subsequently diagnosed with sarcoidosis following histological examination of skin biopsy specimens. In addition to reporting this case, we performed a literature review of 27 cases (24 case reports) of histopathologically diagnosed interferon-α-induced sarcoidosis published between January 2009 and November 2018. Conclusions Among the reviewed cases, 23 (85.1%) cases developed skin lesions and 19 (70.1%) had lung lesions. Only three cases (11.1%) had accompanying eye lesions. Interferon-α therapy was discontinued in 16 cases (52.9%), and the majority exhibited improvement after systemic corticosteroid treatment. There are few reported cases of interferon-α-induced sarcoidosis with uveitis as the initial symptom. However, if uveitis develops during or after interferon-α treatment, it might represent an initial symptom of interferon-α-induced sarcoidosis, as observed in the present case.

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