DeCure for Hypoparathyroidism-deafness-renal disease syndrome
DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for hypoparathyroidism-deafness-renal disease syndrome — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypoparathyroidism-deafness-renal disease syndrome maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for hypoparathyroidism-deafness-renal disease syndrome is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
GATA binding protein 3 (GATA3) — GATA3 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4HC9 · 1.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 37 paediatric patients with primary hypoparathyroidism, 5 (13.5%) had hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome, also called Barakat syndrome. The median age at presentation across the whole cohort was 1.7 months, and mean follow-up was 7.0 years. Among 26 patients examined by renal imaging, 5 (19.2%) had nephrocalcinosis or a renal stone. After 11 months of calcium or calcitriol supplementation, 16 patients (43.2%) discontinued medication; final PTH levels were significantly higher in those with transient hypoparathyroidism than in those with permanent disease.
A 51-year-old man with HDR syndrome presented with severe hypocalcaemia, hyperphosphataemia, severe hypoparathyroidism, low serum magnesium, and mild renal insufficiency. He had left renal aplasia and bilateral sensorineural deafness, plus vitamin D deficiency. Calcium gluconate and magnesium were given intravenously, followed by oral calcium and vitamin D supplements, and hypocalcaemia was corrected. A 19-year-old woman on haemodialysis for chronic renal failure was found to have idiopathic hypoparathyroidism and Hashimoto thyroiditis; the authors note that hypoparathyroidism may be overlooked in chronic renal failure if parathyroid hormone response is not assessed.
A 6-year-old boy with steroid-unresponsive nephrotic syndrome had focal segmental glomerulosclerosis, hypoparathyroidism, and sensorineural deafness. He progressed to end-stage renal failure, was managed with dialysis and cadaveric renal transplantation, and later developed progressive neurological deterioration with mitochondrial myopathy and neuropathy. A family with autosomal dominant hypoparathyroidism and sensorineural deafness but no renal dysplasia is also described; the proband was a 1-month-old with seizures, hypocalcaemia (6.8 mg/dL), hyperphosphataemia (8.9 mg/dL), and normal PTH. Five family members were affected, and sequencing of calcium-sensing receptor and preproPTH genes showed no mutation.
A young woman with congenital deafness and subacute visual loss was found to have primary hypoparathyroidism causing idiopathic intracranial hypertension. She had small bilateral kidneys with tubular loss of magnesium and calcium but normal glomerular filtration rate. The combination of congenital deafness, hypoparathyroidism, and renal dysfunction was diagnosed as Barakat syndrome. What remains missing is systematic prospective data on the natural history of HDR syndrome, standardised protocols for monitoring renal and neurological complications, and any trial of targeted therapy beyond calcium and vitamin D supplementation. Patient stratification by genotype and by presence or absence of renal dysplasia is not yet supported by published evidence.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Endocrinology · 2015 · 48 citations
Diverse genetic aetiologies and clinical outcomes of paediatric hypoparathyroidism
AbstractCONTEXT: Hypoparathyroidism is characterized by hypocalcaemia, hyperphosphataemia, and low or inappropriately normal parathyroid hormone (PTH) levels. Idiopathic or genetic drivers are the predominant causes of hypoparathyroidism in paediatric-age patients. OBJECTIVE: This study investigated the aetiology and clinical course of primary hypoparathyroidism in infancy and childhood. SUBJECTS AND MEASUREMENTS: This study included 37 patients (23 males, 14 females) with primary hypoparathyroidism diagnosed prior to 18 years of age. We analysed aetiologies, initial presentation, age at diagnosis, endocrine and radiological findings, and outcomes. RESULTS: The median age at presentation was 1·7 months (range 1 day-17 years), and the mean follow-up duration was 7·0 ± 5·3 years (range 0·5-16·8 years). Our cohort included 22 cases (59·5%) of 22q11·2 microdeletion syndrome. Other aetiologies included hypoparathyroidism-deafness-renal dysplasia syndrome (5/37, 13·5%) and one patient each with autoimmune polyglandular syndrome type 1, Kearns-Sayre syndrome and Kenny-Caffey syndrome. The remaining 7 (18·9%) patients were classified as idiopathic hypoparathyroidism cases. Among the 15 patients who underwent brain imaging, 5 (33·3%) had basal ganglia calcification. Among the 26 patients examined by renal imaging, 5 (19·2%) had either nephrocalcinosis or a renal stone. After 11 months of calcium or calcitriol supplementation, 16 patients (43·2%) discontinued medication. The final PTH levels were significantly higher in patients with transient hypoparathyroidism than those with permanent hypoparathyroidism. CONCLUSIONS: Identification of the genetic aetiologies of hypoparathyroidism makes it possible to predict patient outcomes and provide appropriate genetic counselling. Long-term treatment with calcium and calcitriol necessitates monitoring for renal complications.
Postgraduate Medical Journal · 2001 · 25 citations · open access
Mitochondrial cytopathy presenting with focal segmental glomerulosclerosis, hypoparathyroidism, sensorineural deafness, and progressive neurological disease
AbstractA 6 year old boy who presented with steroid unresponsive nephrotic syndrome is reported. He was found to have focal segmental glomerulosclerosis and associated hypoparathyroidism and sensorineural deafness. The child progressed to end stage renal failure and was successfully managed by dialysis and cadaveric renal transplantation. He later developed progressive neurological deterioration and mitochondrial myopathy and neuropathy was diagnosed.
Archives of Disease in Childhood · 1980 · 23 citations · open access
Renal tubular acidosis and nerve deafness.
AbstractTwo brothers are described with renal tubular acidosis and nerve deafness: the elder also had rickets and hypokalaemia. The parents were unaffected. Studies of urinary acidification and bicarbonate excretion were consistent with a distal tubular abnormality. This report strengthens the view previously proposed in similar cases that nerve deafness and renal tubular acidosis constitute a genetic entity. Examination for nerve deafness is indicated in any child with renal tubular acidosis.
European Journal of Endocrinology · 1998 · 17 citations · open access
Autosomal dominant familial hypoparathyroidism and sensorineural deafness without renal dysplasia
AbstractOBJECTIVE: A family is described which has a unique combination of autosomal dominant hypoparathyroidism and sensorineural deafness without renal dysplasia. CASE REPORT: The proband was a male infant aged 1 month with episodes of seizures for 20 days. He was born at 35 weeks' gestation without asphyxia, weighing 2040 g. His initial calcium, phosphorus and percentage of tubular reabsorption of phosphorus were 6.8 mg/dl (normal range 8.5-10.5 mg/dl), 8.9 mg/dl (normal range 5.5-7.4 mg/dl) and 96.8% (normal range 85-95%) respectively. He had normal values for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D. No abnormalities were found by renal imaging and a routine renal function study. He showed a brisk plasma cAMP increase in response to human PTH-(1-34) infusion. He had normal karyotype 46, XY, without a microdeletion in chromosome 22q11.2 by an in situ hybridization method. Five family members were affected with hypoparathyroidism with sensorineural deafness with autosomal dominant transmission. The study of calcium-sensing receptor and preproPTH gene showed a normal DNA sequence. CONCLUSION: The combination of familial hypoparathyroidism with sensorineural deafness without renal dysplasia is novel and the cause may be distinct from previously reported familial hypoparathyroidism with sensorineural deafness and renal dysplasia.
Primary Hypoparathyroidism Presenting as Idiopathic Intracranial Hypertension in a Patient With Barakat Syndrome
AbstractUnlike hyperparathyroidism, hypoparathyroidism is rarely encountered in clinical practice. Usually, it results from surgical resection, an autoimmune phenomenon, or an infiltrative process. Under certain circumstances, one may encounter a genetic etiology of hypoparathyroidism, often combined with myriad other syndromic manifestations. We report a case of a young female with congenital deafness and subacute visual loss. Hypocalcemia and primary hypoparathyroidism were subsequently discovered, and the cause of the vision loss was diagnosed as idiopathic intracranial hypertension, likely secondary to severe primary hypoparathyroidism. The patient was also found to have small bilateral kidneys, with tubular loss of magnesium and calcium, yet with a normal glomerular filtration rate. The constellation of congenital deafness, hypoparathyroidism, and renal dysfunction suggests Barakat syndrome, one of the less common causes of syndromic primary hypoparathyroidism.
BMJ Case Reports · 2015 · 2 citations · open access
Vitamin D deficiency in a patient with HDR syndrome
AbstractThe case of a patient with clinical symptoms, laboratory and imaging findings of hypoparathyroidism, sensorineural deafness, renal dysplasia HDR, or Barakat syndrome (hypoparathyroidism, deafness, renal dysplasia), and vitamin D deficiency, is presented. A Caucasian man aged 51 years with a history of chronic hypocalcaemia since childhood, was admitted with hypertonia of the body and extremities, and loss of consciousness. On admission, he was found to have severe hypocalcaemia, hyperphosphataemia, severe hypoparathyroidism, low serum magnesium and mild renal insufficiency. Calcium gluconate was administered intravenously supplemented with magnesium, and the patient recovered consciousness while clinical and laboratory findings improved. Evaluation revealed left renal aplasia and sensorineural deafness affecting both ears. Vitamin D deficiency was also present. He was given calcium and vitamin D supplements orally, and the hypocalcaemia was corrected. This case is described as it is an extremely rare case of HDR syndrome with concurrent vitamin D deficiency.
Coexistence of chronic renal failure, hashimoto thyroiditis and idiopathic hypoparathyroidism: a rare case report
AbstractHypoparathyroidism is an uncommon disease and its coexistence with chronic renal failure is quite rare. Hypocalcemia and hyperphosphatemia are seen in both diseases. Diagnosis of hypoparathyroidism may be overlooked when parathormone response is not evaluated in patients with chronic renal failure. A 19-year-old female patient who had been receiving hemodialysis for 3 years because of chronic renal failure was diagnosed as idiopathic hypoparathyroidism and hashimoto thyroiditis. When her medical records on the first admission and medical history were evaluated, hypoparathyroidism and hashimoto thyroiditis were seen to be present also when she was started hemodialysis. Idiopathic hypoparathyroidism should be suspected in case as absence of parathormone response to hypocalcemia in patients with chronic renal failure. It should be taken into consideration that hashimoto thyroiditis may accompany and required analysis should be done.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
