An Unusual Course of a 2,8-Dihydroxyadeninuria Crystalline Nephropathy Secondary to Adenine Phosphoribosyltransferase Deficiency

Nephron ◽  
2021 ◽  
pp. 1-5
Author(s):  
Nicole Nourié ◽  
Hussein Nassereddine ◽  
Hiba Azar
Keyword(s):  
Genetic Disease ◽  
Autosomal Recessive ◽  
Middle Eastern ◽  
Disease Recurrence ◽  
Gene Variant ◽  
Adenine Phosphoribosyltransferase ◽  
Aprt Gene ◽  
Appropriate Therapy ◽  
Late Stages ◽  
Aprt Deficiency

Adenine phosphoribosyltransferase (APRT) deficiency is a rare disorder caused by an autosomal recessive genetic disease leading to the deposition of 2,8-dihydroxyadenine (2,8-DHA) in the kidney. The disease remains under-recognized, oftentimes diagnosed in late stages of renal insufficiency or a failed kidney allograft with biopsy-proven disease recurrence. Here, we present the case of a 59-year-old middle eastern male patient diagnosed with 2,8-DHA nephropathy after a very unusual presentation, and we show how the initiation of an appropriate therapy slowed down his evolution toward kidney replacement therapies. His disease was found to be secondary to a specific APRT gene variant c.188G>A p (Gly63Asp) also described in 4 other patients, all from middle eastern origins.

scholarly journals APRT deficiency: the need for early diagnosis

2018 ◽  
pp. bcr-2018-225742
Author(s):  
Aamira Huq ◽  
Kushma Nand ◽  
Rajiv Juneja ◽  
Ingrid Winship
Keyword(s):  
Early Diagnosis ◽  
Autosomal Recessive ◽  
Rare Condition ◽  
Autosomal Recessive Disorder ◽  
Signs And Symptoms ◽  
Kidney Donation ◽  
Shortness Of Breath ◽  
Adenine Phosphoribosyltransferase ◽  
Poorly Soluble ◽  
Aprt Deficiency

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder which leads to accumulation of poorly soluble 2,8-dihydroxyadenine in kidneys resulting in nephrolithiasis as well as chronic kidney disease from crystal nephropathy. This report describes a 55-year-old previously fit man who presented with shortness of breath and the investigative pathway that eventually led to a diagnosis of APRT deficiency. Early diagnosis has aided in timely institution of allopurinol, thereby improving his renal function and possibility of weaning off renal replacement therapy. Genetic testing has enabled early identification of other family members at risk and prevention of renal failure by commencing xanthine oxidoreductase (XOR) inhibitors. The issues surrounding kidney donation by a member of this family are also discussed. This case represents the importance of awareness and recognition of the signs and symptoms of this rare condition, complications of which can be easily prevented by early institution of XOR inhibitor therapy.

scholarly journals Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency

2021 ◽  
Author(s):  
Hrafnhildur L. Runolfsdottir ◽  
John A. Sayer ◽  
Olafur S. Indridason ◽  
Vidar O. Edvardsson ◽  
Brynjar O. Jensson ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Autosomal Recessive Disorder ◽  
European Population ◽  
Adenine Phosphoribosyltransferase ◽  
Genomic Databases ◽  
Pathogenic Variants ◽  
Adenine Phosphoribosyltransferase Deficiency ◽  
Variation Database ◽  
The Uk ◽  
Aprt Deficiency

AbstractAdenine phosphoribosyltransferase deficiency is a rare, autosomal recessive disorder of purine metabolism that causes nephrolithiasis and progressive chronic kidney disease. The small number of reported cases indicates an extremely low prevalence, although it has been suggested that missed diagnoses may play a role. We assessed the prevalence of APRT deficiency based on the frequency of causally-related APRT sequence variants in a diverse set of large genomic databases. A thorough search was carried out for all APRT variants that have been confirmed as pathogenic under recessive mode of inheritance, and the frequency of the identified variants examined in six population genomic databases: the deCODE genetics database, the UK Biobank, the 100,000 Genomes Project, the Genome Aggregation Database, the Human Genetic Variation Database and the Korean Variant Archive. The estimated frequency of homozygous genotypes was calculated using the Hardy-Weinberg equation. Sixty-two pathogenic APRT variants were identified, including six novel variants. Most common were the missense variants c.407T>C (p.(Met136Thr)) in Japan and c.194A>T (p.(Asp65Val)) in Iceland, as well as the splice-site variant c.400 + 2dup (p.(Ala108Glufs*3)) in the European population. Twenty-nine variants were detected in at least one of the six genomic databases. The highest cumulative minor allele frequency (cMAF) of pathogenic variants outside of Japan and Iceland was observed in the Irish population (0.2%), though no APRT deficiency cases have been reported in Ireland. The large number of cases in Japan and Iceland is consistent with a founder effect in these populations. There is no evidence for widespread underdiagnosis based on the current analysis.

Homology dependence of targeted recombination at the Chinese hamster APRT locus

1994 ◽  
Vol 14 (10) ◽  
pp. 6663-6673
Author(s):  
J B Scheerer ◽  
G M Adair
Keyword(s):  
Homologous Recombination ◽  
Sequence Homology ◽  
Chinese Hamster Ovary ◽  
Target Gene ◽  
Gene Deletion ◽  
Chinese Hamster ◽  
Adenine Phosphoribosyltransferase ◽  
Aprt Gene ◽  
Logarithmic Relationship ◽  
Targeted Recombination

Using simple linear fragments of the Chinese hamster adenine phosphoribosyltransferase (APRT) gene as targeting vectors, we have investigated the homology dependence of targeted recombination at the endogenous APRT locus in Chinese hamster ovary (CHO) cells. We have examined the effects of varying either the overall length of targeting sequence homology or the length of 5' or 3' flanking homology on both the frequency of targeted homologous recombination and the types of recombination events that are obtained. We find an exponential (logarithmic) relationship between length of APRT targeting homology and the frequency of targeted recombination at the CHO APRT locus, with the frequency of targeted recombination dependent upon both the overall length of targeting homology and the length of homology flanking each side of the target gene deletion. Although most of the APRT+ recombinants analyzed reflect simple targeted replacement or conversion of the target gene deletion, a significant fraction appear to have arisen by target gene-templated extension and correction of the targeting fragment sequences. APRT fragments with limited targeting homology flanking one side of the target gene deletion yield proportionately fewer target gene conversion events and proportionately more templated extension and vector correction events than do fragments with more substantial flanking homology.

Urinary Retention Due to Severe Pseudocystic Mucoid Degeneration of the Prostatic Matrix: A Rare Urologic Manifestation of Cystic Fibrosis

2015 ◽  
Vol 95 (4) ◽  
pp. 486-488
Author(s):  
Gesa Kellermann ◽  
Aristotelis G. Anastasiadis ◽  
Desirée L. Dräger ◽  
Friedrich Prall ◽  
Oliver W. Hakenberg
Keyword(s):  
Cystic Fibrosis ◽  
Urinary Retention ◽  
Genetic Disease ◽  
Autosomal Recessive ◽  
Structural Changes ◽  
Histopathological Examination ◽  
Underlying Disease ◽  
Exocrine Glands ◽  
Mucoid Degeneration ◽  
Prostatic Enlargement

Cystic fibrosis (CF) is an autosomal recessive genetic disease, which is characterized by the production of thick mucus in exocrine glands. The main cause for morbidity and mortality in CF patients is respiratory failure. The gastrointestinal system is also commonly affected. Urologic manifestations of CF include infertility and azoospermia, nephrolithiasis, and stress urinary incontinence. In this report, we describe a 33-year-old male, who presented with recurrent urinary retention due to prostatic enlargement despite his young age. After transurethral resection, the voiding problems resolved. Histopathological examination, however, revealed a severe pseudocystic mucoid degeneration of the prostatic matrix as a cause of his subvesical obstruction. Although these structural changes are most probably due to his underlying disease, detailed histologic features have not been described in the literature.

scholarly journals Monogenic Causes of Strokes

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1855
Author(s):  
Justyna Chojdak-Łukasiewicz ◽  
Edyta Dziadkowiak ◽  
Sławomir Budrewicz
Keyword(s):  
Autosomal Recessive ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Clinical Phenotype ◽  
Single Gene ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Appropriate Therapy

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

scholarly journals Sindrome de allgrove en niños. Reporte de 11 casos

2020 ◽  
Vol 50 (4) ◽  
Author(s):  
María Carmen Álvarez López ◽  
Pedro Coello Ramírez ◽  
Elizabeth García Rodríguez ◽  
Mariana Ordoñez Cárdenas ◽  
Fátima Azereth Reynoso Zarzosa
Keyword(s):  
Adrenal Insufficiency ◽  
Genetic Disease ◽  
High Frequency ◽  
Clinical Characteristics ◽  
Autosomal Recessive ◽  
Allgrove Syndrome ◽  
Documented Case ◽  
Responsible Gene ◽  
Neurological Alterations ◽  
Chronic Vomiting

Background. Allgrove Syndrome is a very rare genetic disease, which is inherited in an autosomal recessive way. The responsible gene is the AAAS, that encodes the protein ALADIN. It occurs most often in children of consanguineous parents. It is characterized by the classic triad of achalasia, alacrima, and adrenal insufficiency due to resistance to ACTH; the presence of two of the three previous manifestation events are required to establish the diagnosis. There is also a high frequency of the neurologic symptoms. Objective. Describe the clinical characteristics, age of presentation and evolution in 11 patients with Allgrove Syndrome. Methods. 11 clinical cases compatible with Allgrove Syndrome of presentation in childhood are retrospectively reviewed. Results. The average age at diagnosis was 5.9 years (range 1-16 years old). There was a predominance of the female sex (n = 7). The most common symptoms were postprandial vomiting and alacrima, present in 100% of the cases at the time of diagnosis. Adrenal insufficiency was not common; it was only documented in one patient. There was consanguinity between parents in 62.5% of the cases. Conclusions. Allgrove Syndrome is an uncommon cause of dysphagia, chronic vomiting and failure to grow in children. In case of any documented case of achalasia it is suggested to question in a directed way the presence of alacrima and adrenal insufficiency data such as seizures, hyperpigmentation of the skin and neurological alterations.

scholarly journals Consanguineous marriages in Finland and their implication for genetic disease

1995 ◽  
pp. 45-53
Author(s):  
Jaakko Ignatius
Keyword(s):  
Rural Areas ◽  
Genetic Disease ◽  
Autosomal Recessive ◽  
Genetic Diseases ◽  
Finnish Population ◽  
Autosomal Recessive Disorders ◽  
Consanguineous Marriages ◽  
The Mean ◽  
Autosomal Recessive Diseases ◽  
Recessive Disorders

The frequency of marriages contracted between individuals with close consanguinity has traditionally been low in Finland. In the 19th and early 20th centuries only 0.1-0.3% of all marriages were contracted between first-cousins (average kinship coefficient 0.0001-0.0002). In genealogical search, however, a remote consanguinity (often beyond 3rd cousins) is frequently found especially in the rural areas and the true level of inbreeding is higher. In Finland, several autosomal recessive diseases are known to be enriched in the population. This unique spectrum of genetic diseases is sometimes called »the Finnish Disease Heritage». To study the implication of close consanguinity for these disorders, information on consanguineous marriages closer than second-cousins was collected from 808 families representing 24 different »Finnish» autosomal recessive disorders. The mean rate of first-cousin marriages was 1.6% (0-20%). Consanguinity (parents second-cousins or closer) was found in 4.2% of the families. For comparison, in 160 families representing three »non-Finnish» autosomal disorders the corresponding figures were 1.9% and 2.5%, respectively. Although these figures are high when compared to the general Finnish population, it can be concluded that close consanguinity is not a significant factor of Finnish genetic diseases.

scholarly journals Congenital Insensitivity to Pain: A Case Report and Review of the Literature

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Leema Reddy Peddareddygari ◽  
Kinsi Oberoi ◽  
Raji P. Grewal
Keyword(s):  
Genetic Disease ◽  
Autosomal Recessive ◽  
Lumbosacral Spine ◽  
Review Of The Literature ◽  
Secondary Complications ◽  
Congenital Insensitivity ◽  
Electrophysiological Studies ◽  
Congenital Insensitivity To Pain ◽  
Insensitivity To Pain ◽  
Spine Disease

Congenital insensitivity to pain (CIP) is a rare autosomal recessive genetic disease caused by mutations in theSCN9Agene. We report a patient with the clinical features consistent with CIP in whom we detected a novel homozygous G2755T mutation in exon 15 of this gene. Routine electrophysiological studies are typically normal in patients with CIP. In our patient, these studies were abnormal and could represent the consequences of secondary complications of cervical and lumbosacral spine disease and associated severe Charcot’s joints.

scholarly journals Netherton’s Syndrome: A Case of Two Male Siblings Diagnosed in Adulthood

2020 ◽  
Vol 12 (1) ◽  
pp. 64-69
Author(s):  
Akshay Flora ◽  
Annika Smith
Keyword(s):  
Genetic Disease ◽  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Correct Diagnosis ◽  
Hair Shaft ◽  
Cutaneous Inflammation ◽  
Erythrodermic Psoriasis ◽  
Timely Fashion ◽  
Congenital Ichthyosiform Erythroderma

Netherton’s syndrome (NS) is a rare autosomal recessive genetic disease caused by a germline mutation in the SPINK5 gene. It is most commonly diagnosed in neonates due to the presence of congenital ichthyosiform erythroderma. Affected individuals will typically also develop a hair shaft abnormality known as trichorrhexis invaginata, severe atopy, and a migratory rash known as ichythyosis linearis circumflexa. The chronicity and severity of NS adversely affects a patient’s quality of life to a large extent. It Is therefore important that this condition is identified early, and treatment to reduce cutaneous inflammation is initiated in a timely fashion. However, due to this condition being relatively rare, a lack of awareness may lead clinicians to misdiagnose it as atopic dermatitis or undifferentiated psoriasis. Clinicians should therefore be aware of the peripheral stigmata that this disease may present as in adulthood, so that a correct diagnosis can be made if it was previously missed. Here we present a case of two male siblings from Jordon who were misdiagnosed since childhood as having erythrodermic psoriasis. Clinical examination of one of the siblings, as an adult, revealed multiple peripheral features associated with NS. Genetic analysis through sanger sequencing was also able to identify a mutation in the SPINK5 gene, confirming the diagnosis.

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