|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 1 | Page : 90-91
Acrodermatitis Enteropathica with Complicated Tubercular Meningitis in a Child with a Novel Mutation of SLC39A4 gene
Anupama Manohar Prasad, Sahana M Srinivas
Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
|Date of Submission||21-Jun-2020|
|Date of Decision||29-Jun-2020|
|Date of Acceptance||14-Jul-2020|
|Date of Web Publication||31-Dec-2020|
Anupama Manohar Prasad
Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Prasad AM, Srinivas SM. Acrodermatitis Enteropathica with Complicated Tubercular Meningitis in a Child with a Novel Mutation of SLC39A4 gene. Indian J Paediatr Dermatol 2021;22:90-1
|How to cite this URL:|
Prasad AM, Srinivas SM. Acrodermatitis Enteropathica with Complicated Tubercular Meningitis in a Child with a Novel Mutation of SLC39A4 gene. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Apr 20];22:90-1. Available from: https://www.ijpd.in/text.asp?2021/22/1/90/305819
Acrodermatitis enteropathica is a rare autosomal recessive zinc deficiency disorder, characterized by triad of acral and periorificial dermatitis, alopecia, and intractable diarrhea. Here, we report a case of inherited acrodermatitis enteropathica with novel homozygous nonsense variation in exon 8, variant c.1308C>A of the SLC39A4 gene in chromosome 8 in a 7-year-old child with complicated tubercular meningitis.
A 7-year-old-boy, born of consanguineous marriage presented with recurrent, itchy skin lesions over perioral, perianal areas, and extremities from 4 months of age. There was a history of recurrent fever, intermittent diarrhea, and loss of hair. There was no history of developmental delay or growth retardation and the child was weaned at 4 months of age. The child had recurrent episodes of seizures, loss of vision, and loss of weight from the past 4 months. He was diagnosed with tubercular meningitis complicated with hydrocephalus and quadriparesis, and underwent ventriculoperitoneal shunt and was started on antitubercular treatment. Family history and sibling history were noncontributory. General physical examination and vitals were normal. On cutaneous examination, few pustules, crusted erosions, and erythematous plaques were seen on perioral, peri-nasal areas, dorsa of hands and feet, and around ankle joints [Figure 1]. Well-defined erythematous scaly plaques were seen over genitals and perianal area [Figure 2]. The child had sparse and brittle hair, loss of eyebrows, and fewer eyelashes [Figure 3]. Mild erythema was seen on the buccal mucosa with angular cheilitis. Nails were brittle and beau's lines were seen on all finger and toe nails, leukonychia, and onychomadesis noted in few nails. Ophthalmic examination revealed loss of perception of light in both eyes secondary to optic atrophy. Central nervous system examination revealed quadriparesis. On investigations, the child had mild anemia. Biochemical profile showed low serum alkaline phosphatase 24 μ/l (up to 500 μ/l), very low serum zinc level <11.47 μg/dl, (70 μg/dl–120 μg/dl), and normal serum biotinidase level (10.30 nmol/ml). Magnetic resonance imaging brain and cerebrospinal fluid analysis were consistent with tubercular meningitis. Genetic analysis done by the next generation sequencing detected novel homozygous mutation in exon 8 of SLC39A4 gene in chromosome 8, resulting in a stop codon and premature truncation of the protein at codon 436 c. 1308C>A (p. Cys436Ter; ENST00000301305.3) thus, confirming the diagnosis of inherited acrodermatitis enteropathica. We were unable to confirm this mutation in parents due to financial constraint. The child was started on oral zinc 3 mg/kg body weight. On follow-up after 6 weeks, the child showed good improvement and reduction in skin lesions. Serum zinc level was raised to 50 μg/dl.
|Figure 1: Erythema, erosions and crusting noted around perinasal and perioral areas|
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|Figure 2: Erythematous to hyperpigmented mild scaly plaque noted over genitals|
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Hereditary form of acrodermatitis enteropathica is caused by mutation in the gene SLC39A4 located on chromosome 8q24.3 which codes for transmembrane protein human zinc/iron-regulated transporter-like protein (hZIP4), expressed in the duodenum and jejunum required for zinc absorption. The SLC39A4 gene covers approximately 4.5 kb of chromosomal region 8q24.3 and consists of 12 exons and 11 introns. Mutations of this gene are spread over the entire gene and include many types of mutations. There are about 31 mutations or unclassified variants of SLC39A4 gene documented since the first description.,
Zhong et al. reported novel compound heterozygous mutations in twins, a missense mutation in exon 5 (c.926G>T), and a splice site mutation occurring in the consensus donor site of intron 5. Our case had mutation in the exon 8 c.1308C>A (P. Cys436Ter), which is not been documented till date.
Zinc deficiency depresses the immune responses, mainly cell-mediated immunity by reducing the capacity to respond to many T-cell-dependent antigens. Although superinfections with staphylococcus, candida and Pseudomonas aeruginosa are common, tuberculosis in hereditary acrodermatitis enteropathica is rarely reported. Mondal et al. reported a case of disseminated tuberculosis in a 4-year-old child with acrodermatitis enteropathica but genetic confirmation was not done in their case. The complicated tubercular meningitis in our case, may possibly point this novel mutation's association toward severe immunodeficiency.
The child responded well to oral zinc therapy and was advised for lifelong zinc supplementation. Unfortunately, in our case, vision loss and quadriparesis were permanent sequelae. The child was advised regular follow-up for monitoring serum zinc levels every 3–6 months.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]