Brandt syndrome (BS) is an autosomal recessive inborn error of metabolism that usually occurs in early childhood, particularly in children who have recently been weaned off breast milk, or a few weeks after birth in children who are not breast fed. Symptoms are primarily due to zinc deficiency, secondary to reduced absorption of zinc [1]. Acquired deficiency of this mineral is seen in adulthood, and the signs are the same as those of BS [2] [3] [4]. Zinc deficiency can be caused by various factors, like restricted diet, gastrointestinal pathologies such as celiac disease, alcoholism, excessive intake of phytates, burns and renal disease [5] [6].

The clinical triad for BS is dermatitis, diarrhea, and alopecia, although few patients present in this way [7]. Dermatitis characteristic of BS includes periorificial, around the mouth and eyes, and acral dermatitis, which affects the extremities. Skin lesions may be pustular, vesicular, erythematous and crusted. In addition, they have a clear demarcation and may resemble eczema or psoriasis. As the condition progresses, lesions may spread to other areas of the body such as the buttocks and thighs. Alopecia is noted in the hair as well as eyebrows and eyelashes. Other dermatological symptoms are dysmorphic nails and superimposed bacterial or fungal infection. The latter may make the correct diagnosis even more difficult to ascertain.

Involvement of mucosal surfaces may manifest in the form of blepharitis, conjunctivitis and inflamed gums and stomatitis [8]. Furthermore, patients may also show changes in mood, photophobia, increased susceptibility to infection, mental dullness, a reduced sense of taste and anorexia. In infants, additional symptoms comprise of failure to thrive, growth retardation and irritability.

• Splenomegaly

  Congenitally anemic W/Wv mice reconstituted with bone marrow cells transduced with the retroviral vector developed a syndrome characterized by anemia, transient granulocytosis, hypoalbuminemia, and polyclonal hypergammaglobulinemia, with marked splenomegaly [jci.org]

  […] dysfunction 0005435 Infantile onset Onset in first year of life Onset in infancy [ more ] 0003593 Irritability Irritable 0000737 Lethargy 0001254 Low alkaline phosphatase Decreased serum alkaline phosphatase 0003282 Recurrent candida infections 0005401 Splenomegaly [rarediseases.info.nih.gov]

• Weight Loss

  It presents as erythematous skin lesions, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, cheilitis, neuropsychiatric disturbances, steatorrhea and diarrhea. [explainmedicine.com]

  Growth retardation, alopecia, weight loss and recurrent infections were prevalent in toddlers and schoolchildren. Spontaneous remission may occur at adolescence. 2. The severity of symptoms also varies. [ncbi.nlm.nih.gov]

  Contact your doctor right away if you have weight loss when you are not trying, bloody stools, fever, or severe pain. [ufhealth.org]

  Complications may include: Failure to locate the tumor during surgery Intestinal bleeding or hole (perforation) from ulcers in the stomach or duodenum Severe diarrhea and weight loss Spread of the tumor to other organs Call your health care provider if [medlineplus.gov]

• Malnutrition

  In congenital acrodermatitis enteropathica these lesions begin to appear after weaning is started. [1,4] History of malnutrition Malnutrition especially zinc deficiency leads to the development of acquired acrodermatitis enteropathica. [2] Positive family [explainmedicine.com]

  Histopathologic findings are typically indistinguishable from other forms of malnutrition dermatitis. [bmcdermatol.biomedcentral.com]

  We assume that in our patient the skin lesions were the result of malnutrition, rather than being primarily associated with the underlying metabolic disease. [ijp.mums.ac.ir]

• Short Stature

  AE is associated with short stature, anaemia, skin hyperpigmentation, hepatosplenomegaly, hypogonadism, poor wound healing, immune deficiency, recurrent bacterial and fungal infections due to immune defect. [medical-dictionary.thefreedictionary.com]

  Growth delays continue after birth (postnatal), resulting in short stature (dwarfism). [rarediseases.org]

  stature Decreased body height Small stature [ more ] 0004322 30%-79% of people have these symptoms Blepharitis Inflammation of eyelids 0000498 Cheilitis Inflammation of the lips 0100825 Conjunctivitis Pink eye 0000509 Emotional lability Emotional instability [rarediseases.info.nih.gov]

• Recurrent Infection

  Growth retardation, alopecia, weight loss and recurrent infections were prevalent in toddlers and schoolchildren. Spontaneous remission may occur at adolescence. 2. The severity of symptoms also varies. [ncbi.nlm.nih.gov]

  Mother revealed similar cutaneous manifestations and chronic diarrhea in her first child, who succumbed to recurrent infections at the age of 6 months. [ijpd.in]

• Death in Infancy

  If untreated, the condition can result in death during infancy or early childhood. Symptoms Symptoms of this condition include growth retardation, diarrhea, hair loss, and a red skin rash. Skin around the fingernails may be red and swollen. [uofmhealth.org]

• Diarrhea

  […] or malabsorption History of refractory diarrhea or malabsorption is present in many patients with acrodermatitis enteropathica. [explainmedicine.com]

  Management Oral zinc. acrodermatitis enteropathica Congenital zinc deficiency An AR condition characterized by dermatitis and diarrhea; the dermatitis affects the cheeks, elbows, knees, periorbital and perianal regions, and is accompanied by hair loss [medical-dictionary.thefreedictionary.com]

  Diarrhea, generalized alopecia and Beau-Reil lines on the nails are frequent manifestations. Paronychia, conjunctivitis, blepharitis and erythematous oral mucous membranes are also sometimes observed. [orpha.net]

  The primary complication associated with zinc therapy is diarrhea. This may be minimized by administering zinc gluconate, which is usually better tolerated, with less diarrhea than seen with zinc sulfate. [clinicaladvisor.com]

• Failure to Thrive

  Case2: Two-month-old male patient was admitted with diffuse erythemateous and pathcy, exfoliated skin eruptions, anemia, hypoalbuminemia, edema, diarrhea, failure to thrive and bronchiolitis history.He was thought to be CF; treated with PERT and skin [erj.ersjournals.com]

  Diets with high amounts of phytate, chronic alcoholism, total parenteral nutrition, anorexia nervosa and bulimia nervosa are other causes of zinc deficiency. [1,5] Failure to thrive Failure to thrive is also a common feature seen in acrodermatitis enteropathica [explainmedicine.com]

  The disorder is characterized by intermittent simultaneous occurrence of diarrhea and dermatitis with failure to thrive. [genome.jp]

  Inherited vesiculobullous disorder characterized by intermittent simultaneous occurrence of diarrhea and bullous dermatitis (dry lesions surrounding the mouth, ears, nose, and eyes, but also affecting the fingers, feet, and knees) and failure to thrive [accessanesthesiology.mhmedical.com]

  Other features associated with severe and chronic zinc deficiency include failure to thrive, mental slowness, photophobia, hypogeusia, anemia, poor wound healing, hypogonadism in males, and delayed puberty. [orpha.net]

• Chronic Diarrhea

  History of excessive irritability and chronic diarrhea was present. The parents had no history of consanguinity. [ijpd.in]

  Chronic diarrhea leads to malabsorption and acquired acrodermatitis enteropathica. Secondary causes of acquired zinc deficiency includes chronic pancreatitis, malabsorption syndromes, blind loop syndrome and cirrhosis. [explainmedicine.com]

  Blistering, generalized Blisters [ more ] 0008066 Abnormal eyebrow morphology Abnormality of the eyebrow 0000534 Alopecia Hair loss 0001596 Cerebral cortical atrophy Decrease in size of the outer layer of the brain due to loss of brain cells 0002120 Chronic [rarediseases.info.nih.gov]

• Cheilitis

  She reported that the rash started on her feet and mouth before spreading to her knees and was accompanied by lower extremity swelling, cheilitis, and glossitis. [cureus.com]

  It presents as erythematous skin lesions, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, cheilitis, neuropsychiatric disturbances, steatorrhea and diarrhea. [explainmedicine.com]

  […] and angular cheilitis. [elsevier.es]

  Mucosal features include red glossy tongue, angular cheilitis and mouth ulcers. Wound healing is impaired. [dermnetnz.org]

  The lesions may develop over the arms and legs as well as the anogenital and periorificial areas. 5 Other notable manifestations that may present early in the course of AE include angular cheilitis followed by paronychia. [mdedge.com]

• Oral Ulcers

  No oral ulcers were present. [mdedge.com]

• Sore Mouth

  The lesions were accompanied with sore mouth and hair loss. [ijdvl.com]

• Alopecia

  AE is characterised by a triad of periorificial and acral dermatitis, diarrhoea and alopecia. [omicsonline.org]

  Alopecia is noted in the hair as well as eyebrows and eyelashes. Other dermatological symptoms are dysmorphic nails and superimposed bacterial or fungal infection. The latter may make the correct diagnosis even more difficult to ascertain. [symptoma.com]

  The alopecia diffusely affects the eyelashes, eyebrows and scalp. As described in the case, secondary infection by candida albicans or staphylococcus aureus may complicate the disease. [longdom.org]

  Cutaneous aspects after 2 months of treatment, with remission of periorificial lesions and alopecia. [ncbi.nlm.nih.gov]

  It is characterized by skin lesions on acral and periorificial areas and may be associated to alopecia, diarrhea and increased frequency of infections. [termedia.pl]

• Blister

  These blisters would not be intact, may worsen in warmer climates and would be more evident on exposed areas such as the feet, elbows, hands and knees. The blisters would heal with thickening of the skin on soles and palms with no scarring evident. [omicsonline.org]

  […] gastrointestinal disturbances such as diarrhea, as well as total alopecia. ac·ro·der·ma·ti·tis en·ter·o·path·'i·ca [MIM*201100] a progressive hereditary defect of zinc metabolism in young children (onset, 3 weeks-18 months); often manifests first as a blistering [medical-dictionary.thefreedictionary.com]

  Later they become crusted and blisters appear. Rupture of blisters expose the purulent eroded skin lesions. [1,2,4] Alopecia Diffuse hair loss in scalp, eye lashes and eye brows can be seen. [explainmedicine.com]

  Acrodermatitis enteropathica Other names Acrodermatitis enteropathica, zinc deficiency type[1] Acrodermatitis enteropathica inheritance Specialty Endocrinology Symptoms Dry skin, Emotional lability, Blistering of skin[2] Causes Mutation of the SLC39A4 [en.wikipedia.org]

  This case report describes AE which manifested in a similar way to other blistering skin disorders, but showed a dramatic clinical improvement to oral zinc therapy. [longdom.org]

• Eczema

  Symptoms are a result of chronic zinc deficiency and include eczema-like or crusty skin lesions that are susceptible to infections, loss of hair, diarrhea, and failure to grow. [sema4.com]

  In addition, they have a clear demarcation and may resemble eczema or psoriasis. As the condition progresses, lesions may spread to other areas of the body such as the buttocks and thighs. [symptoma.com]

  […] granuloma Non-hereditary acrodermatitis enteropathica Papular acrodermatitis of childhood Papular acrodermatitis, childhood Papulosquamous dermatosis Papulosquamous disorder Perleche Pitted keratolysis Protothecosis of skin Pustular bacterid Pustular eczema [icd9data.com]

  A biopsy from an early skin lesion is not specific as the histology may be similar to eczema or psoriasis. Spongiosis with epidermal pallor may be seen initially. [dermnetnz.org]

• Skin Rash

  The main symptoms can also include growth retardation, the presence of a persistent diarrhea, the loss of hair and balding and the presence of a red skin rash on the body of the child. [herbs2000.com]

  Rapid resolution of the skin rash ( Figure 5 ) as well as weight gain and improvement in motor skills and mentation occurred. Two months after initiating therapy, the serum zinc increased to 67 mcg/dL and the alkaline phosphatase was 90 U/L. [consultant360.com]

  The febrile episodes are commonly accompanied by hepatosplenomegaly, lymphadenopathy, abdominal symptoms, arthralgia and skin rashes. Life expectancy is often compromised. [ojrd.biomedcentral.com]

  […] manifestations suggest a possible NCGS: headache or migraine, "foggy mind", chronic fatigue,[64] fibromyalgia,[65][66][67] joint and muscle pain,[64][65][68] leg or arm numbness,[64][65][68] tingling of the extremities,[64][68] dermatitis (eczema or skin [en.wikipedia.org]

• Irritability

  Children are highly irritable. [explainmedicine.com]

  In the acute phase, irritability and emotional disturbances are evident due to wasting (atrophy) of the brain cortex. synonyms Acrodermatitis Enteropathica UMLS Acrodermatitis enteropathica, Acrodermatitis enteropathica syndrome, Brandt syndrome, Brandt's [dermis.net]

  The first sign of response to treatment less irritability. Shortly after that, improvement in skin lesions is noted. While on therapy, regular monitoring of certain parameters is also required. [statpearls.com]

  […] in the gastrointestinal absorption of zinc typically presents when the affected infant is weaned from breast feeding acquired form due to nutritional zinc deficiency, e.g. in premature infants who receive prolonged parenteral alimentation Features: irritability [gpnotebook.co.uk]

  After zinc replacement, the skin lesions heal within one to two weeks, diarrhoea ceases, and irritability and depression of mood improve within 24 hours. Secondary bacterial and/or fungal infection of lesions require appropriate antibiotic therapy. [dermnetnz.org]

• Behavior Problem

  Parent management training is a highly effective form of psychotherapy that teaches parenting skills to reduce their child's behavior problems. [en.wikipedia.org]

Diagnosis of BS incorporates clinical assessment as well as laboratory studies. In a patient suspected to have BS because of their clinical symptoms, serum zinc levels, which may be depleted, can be calculated. A value less than 50 micro-grams per deciliter implies BS [5]. Measuring zinc in the hair and urine is also done, but this is not common [7]. Serum alkaline phosphatase levels may be low. If it is in the normal range, however, this does not rule out BS. Further, the administration of zinc and an improvement in symptoms is used to confirm the diagnosis.

Genetic testing for the mutation in the solute carrier family 39 member 4 (SLC39A4) gene are not routinely available.

Light and electron microscopy may be utilized in the analysis of biopsy samples. A breast feeding infant's mother can have her breast milk screened for low zinc, as an inadequate concentration in breast milk may be the cause of zinc deficiency in an infant [9].

Histological examination of lesions yields findings such as neutrophils in the epidermal layer as well as abnormal keratinization of the epidermis, pallor, tissue necrosis and hyperplasia. However, such details may also be noticed in other nutritional diseases.

• Alkaline Phosphatase Decreased

  [ more ] 0003593 Irritability Irritable 0000737 Lethargy 0001254 Low alkaline phosphatase Decreased serum alkaline phosphatase 0003282 Recurrent candida infections 0005401 Splenomegaly Increased spleen size 0001744 Tremor 0001337 Showing of 44 | Last [rarediseases.info.nih.gov]

Management and treatment There is no cure for AE. In the majority of cases, zinc supplementation therapy results in the disappearance of AE symptoms, but this treatment is life-long and relapses can occur. [orpha.net]

He is currently continuing his zinc treatment, and he will be undergoing regular check-ups. Cutaneous aspects after 2 months of treatment, with remission of periorificial lesions and alopecia. [ncbi.nlm.nih.gov]

Prognosis With adherence to life-long zinc substitution therapy, the prognosis is good. Only when infants are left untreated can the disease be fatal. The documents contained in this web site are presented for information purposes only. [orpha.net]

Without treatment, the prognosis of acrodermatitis enteropathica is bad, with mortality occurring between four and five years of age. In the acute phase, irritability and emotional disturbances are evident due to wasting of the brain cortex. [streetdirectory.com]

Zinc, and other nutritional, deficiencies in adults are often a manifestation of an underlying malabsorptive etiology. [bmcdermatol.biomedcentral.com]

Symptomatic treatment is any medical therapy of a disease that only affects its symptoms, not its cause, i.e., its etiology. [en.wikipedia.org]

Etiology AE is due to a mutation in the SLC39A4 gene (8q24.3) that encodes a zinc transporter protein (called the Zip4 transporter). [orpha.net]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

Topics covered include the history of the disease, categories of the disorder, molecular analysis, epidemiology, effects on body systems, disorder symptoms, and treatment. [blunck-medical-books.de]

Summary Epidemiology The prevalence of AE is unknown. It is more common in the North-West of Tunisia. [orpha.net]

الصفحة 450 - Pathophysiological mechanisms involved in genesis and spread of muscular tension in occupational muscle pain and in chronic musculoskeletal pain syndromes: a hypothesis. ‏ [books.google.com]

^ a b c d e "Acrodermatitis Enteropathica: Background, Pathophysiology, Epidemiology". 2017-01-10. ^ Sehgal, V. N.; Jain, S. (2000-11-01). "Acrodermatitis enteropathica". Clinics in Dermatology. 18 (6): 745–748. doi:10.1016/s0738-081x(00)00150-4. [en.wikipedia.org]

Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 21. Theise ND. Liver and gallbladder. In: Kumar V, Abbas AK, Fausto N, Aster JC, eds. [ufhealth.org]

Acquired zinc deficiency can manifest at any age.[5] Pathophysiology Zinc plays an important role in cellular processes, being an integral part of various metalloenzymes and transcription factors. [statpearls.com]

How can this disease be prevented? Increased zinc supplementation in affected women during pregnancy will prevent subtle or overt expression of AEZ because of the increased demand for zinc. [clinicaladvisor.com]

Emphasis is placed on early and adequate zinc replacement to effectively prevent or reverse this entity. [ncbi.nlm.nih.gov]

An early diagnosis and prompt treatment of AE reduces mortality and prevents the long-term consequences of zinc deficiency. [longdom.org]

This is accomplished through the stabilization of cell membranes by reducing free radical production and the prevention of lipid peroxidation. [consultant360.com]

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