Ocular manifestations of autosomal recessive Alport syndrome

Ocular abnormalities are common in X-linked Alport syndrome, but they have not been studied in patients with the rarer autosomal recessive disease. We have examined the eyes of a family with autosomal recessive Alport syndrome. Four of the eight offspring of a consanguineous marriage had renal failure and deafness by the age of 20 years. The diagnosis of Alport syndrome was confirmed on the ultrastructural demonstration of a lamellated glomerular basement membrane (GBM) in one affected family member. Autosomal recessive inheritance was suggested by the lack of linkage to the COL4A5/COL4A6 locus, and by linkage to the COL4A3/COL4A4 locus. All four affected family members had anterior lenticonus (or had had a lens replacement for this) and the three who were examined had a dot-and-fleck retinopathy. Neither of the two unaffected offspring who were examined nor the father had these abnormalities. The ocular manifestations of autosomal recessive Alport syndrome are probably identical to those for the X-linked form. Although the mutations in these diseases affect genes for different type IV collagen chains, these chains occur together in the basement membranes of the kidney, eye and ear, and abnormalities in any one may result in the same clinical phenotype.     

Orofacial manifestations of Melkersson-Rosenthal syndrome. A study of 42 patients and review of 220 cases from the literature

We investigated orofacial manifestations in 42 patients with Melkersson-Rosenthal syndrome who were examined at our institution between 1965 and 1990. Patient histories and histologic and clinical findings were reviewed in detail. These data were compared with the oral findings in 220 cases that were reported in the literature between 1965 and 1990. There were 28 females in our study. The age at onset of signs and symptoms varied widely with a mean of 33.8 years. Most frequent initial signs were labial edema, facial swelling, and Bell's palsy. During the course of the disease, 75% of all patients had labial swelling, 50% had facial edema, and 33% had Bell's palsy. Swelling, erythema, or painful erosions that affected the gingiva, buccal mucosa, palate, or tongue were common intraoral symptoms. A comparison with patients reported in the literature revealed a similar frequency of extraoral symptoms but more prevalent intraoral symptoms in our patients.     

Alport syndrome in the light of current molecular genetics

Alport syndrome is a hereditary nephropathy, inconstantly associated with sensorineural deafness and ocular abnormalities. These manifestations result from a structural defect in type IV collagen. Recent genetic advances have provided a molecular basis for the two main subsets of the disease, namely the X-linked and the autosomal recessive forms. It has just been shown that the autosomal dominant entity known as benign familial haematuria is actually due to a heterozygote mutation of the gene accounting for the autosomal recessive form of Alport syndrome. The genetic breakthrough has already clinical and pathophysiological implications.     

Psychotic manifestations complicating surgical operation in the ocular region

The authors report ten observations as well as the results of an investigation conducted by ophtalmologists and psychiatrists with intention of better understanding clinical, physiological and psychological problems, provoked by occurance of complications stemming from psychoses which are the result of ophtamological complications. They conclude that it is necessary to form accurate distinctions with regard to the total manifestations of the malady "black patch delirium". They emphasize the fact that its manifestations are not an appanage of the aged ; they especially insist upon not only the role of visual disorientation but also of the social factors which are united with restrictions, beyond those of motor, control and biological imvalances. With regard to etiopathology they acknowledge a need for a combination of organogenic and psychodynamic models to account for each case ; a certain number of communal points can be found : subjects (declined in physical and metal capacities), there is a rapid weaking of the external comportment, resulting in an imptiness, which must be compensated for by a fantasy life or some other physiopathological mecanisms.     

The ocular manifestations of Beh?et's disease

Of 32 patients with Beh?et's disease, 21 had uveitis. The uveitis was seldom the initial manifestation of systemic disease, but once established, it tended to become chronic and bilateral, involving the anterior and posterior segments. Hypopyon was a relatively uncommon occurrence in this series. All patients with uveal inflammation had obvious cellular reactions within the vitreous body. Other posterior segment manifestations of the disease included localized retinal edema, macular edema, disc edema, retinal pigmentary changes, and accumulation of exudative material in the deep retina. One patient developed a necrotizing retinitis with deep retinal exudation and subsequent retinal detachment. Occlusions of retinal vessels were common. Neuro-ophthalmologic manifestations of Beh?et's disease included cranial nerve palsies, a homonymous hemianopic field defect, and papillitis.     

Lymphocutaneous syndrome. A review of non-sporothrix causes

The lymphocutaneous syndrome can be caused by a number of diverse microorganisms requiring very different antimicrobial therapy for resolution. The epidemiology and geographic occurrence of the infection often can provide important first clues to the microbiologic etiology. Accurate diagnosis can be accomplished usually by punch or wedge biopsy of a primary lesion or proximal subcutaneous nodule submitted for histopathologic examination and culture. The microbiology laboratory staff should be alerted to the diagnostic possibilities so that appropriate cultural and incubation techniques, procedures, and precautions can be initiated. Provision of a correct microbiologic diagnosis and institution of appropriate antimicrobial therapy will result in a complete cure in almost all instances. Adjunctive surgical debridement may be required for certain organisms such as Nocardia or Mycobacterium chelonae.     

Alport syndrome: from bedside to genome to bedside

Alport syndrome is a genetic disorder of basement membranes manifested clinically by a progressive nephropathy and, in many families, sensorineural hearing loss and ocular lesions. During the 1980s evidence was amassed indicating type IV (basement membrane) collagen as the defective protein in Alport This hypothesis was confirmed in 1990 by the cloning of the X-chromosomal gene COL4A5, which encodes the alpha 5 chain of type IV collagen, and the discovery of mutations in this gene in many Alport kindreds. The results of results of recent studies suggest that the alpha 5(IV) chain forms a distinct collagenous network with the alpha 3 and alpha 4 chains of type IV collagen and that mutations in alpha 5(IV) may prevent the normal incorporation of alpha 3(IV) and alpha 4(IV) into basement membranes. Renal biopsy remains an important modality for making the diagnosis of Alport syndrome, but may eventually be replaced by molecular genetic techniques. Posttransplant anti-glomerular basement membrane nephritis occurs rarely in Alport patients and may be restricted to a subgroup with particular COL4A5 mutations. It is not clear why COL4A5 mutations result in glomerulosclerosis and renal failure, or whether this process may be slowed through dietary or pharmacologic intervention.     

Autoimmune manifestations of the Wiskott-Aldrich syndrome

OBJECTIVE: To describe and review the autoimmune features and typical manifestations of Wiskott-Aldrich syndrome (WAS). DESIGN: Case series and review of the literature. SETTING: Tertiary care medical center and pediatric referral center. PATIENTS: The presentation, diagnosis, and management of two cases are reported. In addition to the typical features of WAS, the first patient had hemolytic anemia, arthritis, leukocytoclastic vasculitis, and colitis. The second patient had colitis and arthralgias. Detailed review of features and therapeutic options in WAS as exemplified by these two patients are presented. Both patients had bone marrow transplantation, the only definitive treatment for WAS. CONCLUSIONS: WAS has variable clinical and autoimmune manifestations. Diagnosis must be suspected in a boy with small, decreased number of platelets and autoimmune problems or infections. Bone marrow transplantation is the only successful mode of treatment for all aspects of WAS.     

Alport syndrome with neurofibromatosis type-I: a case report

We report a 9-year-old boy with repeated fractures of the tibia from age 6 months and microscopic hematuria from age 2 years. His maternal family has a history of nephritis and his paternal family has neurofibromatosis type-I (NF-I). The boy's renal biopsy revealed an irregular attenuation and splitting of the glomerular basement membrane. The skin biopsy was stained with monoclonal antibody against the alpha 5 chain of type IV collagen; the epidermal basement membrane was negative in the boy and segmentally positive in the boy's mother. We conclude that the patient inherited Alport syndrome from his mother and NF-I from his father. We postulate this was a chance association and that this case does not suggest any relationship between the two diseases.     

Rheumatic manifestations related to acrodermatitis chronica atrophicans. A review of four cases

BACKGROUND: Acrodermatitis chronica atrophicans is a delayed manifestation of Lyme disease caused by a Borrelia burgdorferi subspecies, B. afzelii. Although rheumatic manifestations are rare, they can result in deformities of the fingers and toes if they are not treated promptly. METHODS: We report four cases of acrodermatitis chronica atrophicans seen over a 15-year period. RESULTS: Two patients had a noninflammatory unilateral knee effusion and one had swelling of the dorsum of one hand. Antimicrobial therapy was followed by a full recovery in the three patients who received an early diagnosis. The remaining patient, a 63-year-old woman, had swelling and dysesthesia in the fingers of both hands. She developed finger deformities over a period of two years. Although the swelling resolved under antimicrobial therapy, she had persistent reducible deformities of the fingers consistent with Jaccoud's arthropathy. CONCLUSION: The diagnosis of acrodermatitis chronica atrophicans rests on a history of a tick bite, a suggestive skin biopsy histology and a positive Western blot for B. afzelii. A positive response to antimicrobial therapy is also required. Acrodermatitis chronica atrophicans, a common condition in central and northern Europe, can cause joint manifestations and persistent finger deformities in the absence of early treatment.     

Clinical manifestations of vasculitis in patients with solid tumors. A case report and review of the literature

Vasculitis is characterized by inflammatory changes and necrosis of blood vessels. Involvement of arteries and veins of diverse sizes throughout the body is possible and results in a multiplicity of clinical manifestations. Primary and secondary forms of vasculitis exist. Secondary vasculitis has been linked to several processes, including infections, drugs, and allergic, rheumatologic, and neoplastic disease. The majority of patients with malignant neoplasm-associated vasculitis who have been described had hematologic neoplasms. We report a patient with adenocarcinoma of the colon and vasculitis and review the 36 cases of vasculitis in patients with solid tumors documented in the world literature. The most common malignant neoplasms were non-small-cell lung cancer and prostate, breast, colon, and renal cancer. Cutaneous leukocytoclastic vasculitis and nerve and muscle microvasculitis were the most frequently observed vasculitic subtypes. Importantly, in 71% of the cases, manifestations of vasculitis appeared before or concurrent with the initial recognition or the relapse of the tumor. Management strategies that met with success in at least half the patients in whom they were used included corticosteroids, cyclophosphamide, and treatment of the underlying cancer. Prognosis may be primarily related to the ability to control the malignant neoplasm, as most of the patients who died did so because of tumor progression.     

Determination of the genomic structure of the COL4A4 gene and of novel mutations causing autosomal recessive Alport syndrome

Autosomal recessive Alport syndrome is a progressive hematuric glomerulonephritis characterized by glomerular basement membrane abnormalities and associated with mutations in either the COL4A3 or the COL4A4 gene, which encode the alpha3 and alpha4 type IV collagen chains, respectively. To date, mutation screening in the two genes has been hampered by the lack of genomic structure information. We report here the complete characterization of the 48 exons of the COL4A4 gene, a comprehensive gene screen, and the subsequent detection of 10 novel mutations in eight patients diagnosed with autosomal recessive Alport syndrome. Furthermore, we identified a glycine to alanine substitution in the collagenous domain that is apparently silent in the heterozygous carriers, in 11.5% of all control individuals, and in one control individual homozygous for this glycine substitution. There has been no previous finding of a glycine substitution that is not associated with any obvious phenotype in homozygous individuals.