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Last update 08 May 2025

Hypotonia-Cystinuria Syndrome

Last update 08 May 2025

Basic Info

Synonyms

CYSTINURIA WITH MITOCHONDRIAL DISEASE, Cystinuria with Mitochondrial Disease, HCS

+ [11]

Introduction

A rare, genetic disorder of amino acid absorption and transport, characterized by generalized hypotonia at birth, neonatal/infantile failure to thrive (followed by hyperphagia and rapid weight gain in late childhood), cystinuria type 1, nephrolithiasis, growth retardation due to growth hormone deficiency, and minor facial dysmorphism. Dysmorphic features mainly include dolichocephaly and ptosis. Nephrolithiasis occurs at variable ages.

Clinical Trials associated with Hypotonia-Cystinuria Syndrome

NCT02640443

/ Unknown statusPhase 2IIT

Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (In Dutch: Sulfamethoxazole Ter Behandeling Van Primaire PREPL deficiëntie)

The investigators will evaluate whether sulfamethoxazole, a sulfamide antibiotic, improves the symptoms of primary PREPL deficiency (hypotonia-cystinuria syndrome and isolated PREPL deficiency).

Start Date01 Oct 2015

Sponsor / Collaborator

Universitair Ziekenhuis Brussel

[+1]

EUCTR2013-005475-41-BE

/ Not yet recruitingPhase 2IIT

Sulfamethoxazole treatment of primary PREPL deficiency - Sulfamethoxazole for HCS

Start Date05 Nov 2014

Sponsor / Collaborator-

NCT02263781

/ Active, not recruitingNot ApplicableIIT

PREPL in Health and Disease

Evaluation of PREPL activity in healthy controls and known or possible PREPL deficient patients

Start Date01 Oct 2014

Sponsor / Collaborator

Katholieke Universiteit Leuven

100 Clinical Results associated with Hypotonia-Cystinuria Syndrome

100 Translational Medicine associated with Hypotonia-Cystinuria Syndrome

0 Patents (Medical) associated with Hypotonia-Cystinuria Syndrome

498

Literatures (Medical) associated with Hypotonia-Cystinuria Syndrome

01 Jul 2025·Neuropharmacology

Activated mTORC1 signaling pathway aggravates cisplatin induced oxidative damage by inhibiting autophagy in mouse cochlear hair cells

Article

Author: Tang, Jie ; Qu, Jia-Xi ; Qi, Xiao-Fei ; Wen, Yin-Chuan ; Pan, Jing ; Xu, Na-Na ; Shu, Fan

Platinum-based antitumor drugs, such as cisplatin and carboplatin, are well-known for their severe ototoxicity. The ototoxic effects of these drugs are primarily attributed to oxidative stress induced damage within cochlear hair cells (HCs), leading to cell death and subsequent irreversible hearing loss. Over the past decade, studies have demonstrated that upregulating autophagy levels in HCs can greatly alleviate the death of cochlear HCs as part of the oxidative damage induced by ototoxic drugs. However, the molecular mechanisms by which platinum-based drugs affect autophagy and ultimately lead to HCs death remain unclear. In the present study, we investigated the effects of cisplatin on the mTOR signaling pathway, a critical regulator of autophagy, in cochlear explants of mice. Our results indicated that while cisplatin enhances autophagy activity initially, it also activates mTOR Complex1 (mTORC1) within HCs. The persistent activation of mTORC1 inhibits autophagy in HCs, resulting in the accumulation of reactive oxygen species and leading to cell death. Further pharmacological experiments confirmed the protective role of rapamycin, a specific mTORC1 inhibitor, highlighting the importance of autophagy in combating cisplatin-induced ototoxicity. Our findings suggest that modulating the mTOR signaling pathway to regulate autophagy could be an effective strategy for preventing cisplatin-induced ototoxic damage.

01 Jun 2025·Bone Reports

Bone mineral density and microarchitecture improvement in a young patient with Hajdu-Cheney syndrome and autosomal dominant polycystic kidney disease treated with alendronate

Article

Author: Watanabe, Elieser Hitoshi ; Onuchic, Luiz Fernando ; Pereira, Rosa Maria Rodrigues ; Caparbo, Valeria de Falco ; Franco, André Silva

IntroductionOsteoporosis, typically seen in postmenopausal women, can also affect younger individuals, a condition known as Early-Onset Osteoporosis (EOOP). EOOP may be secondary to various conditions or arise from rare genetic disorders such as Hajdu-Cheney Syndrome (HCS), characterized by systemic bone involvement and fragility fractures.Case ReportA 14-year-old male presented with a distal left femur fragility fracture. His medical history included spina bifida and bilateral tarsal coalition, with no family history of osteoporosis, and polycystic kidneys associated with a positive family history of autosomal dominant polycystic kidney disease (ADPKD). Laboratory tests were unremarkable, but dual X-ray absorptiometry (DXA) revealed low bone mineral density (BMD), and high resolution peripheral quantitative computed tomography (HR-pQCT) showed decreased volumetric bone density (vBMD), particularly in the cortical bone. At age 17, his kidneys were cystic and mildly enlarged. Whole exome sequencing revealed a pathogenic variant in NOTCH2, confirming the diagnosis of HCS, and a very likely causative variant in PKD1, supporting the diagnosis of ADPKD.The treatment regimen included weekly alendronate, impact exercise, a calcium-rich diet, and vitamin D supplementation. After 3 years, follow-up DXA and HR-pQCT demonstrated significant improvements in BMD and vBMD, mainly in the cortical bone.DiscussionThis case highlights the effectiveness of alendronate in managing osteoporosis in a patient with HCS and ADPKD, despite the current lack of strong supportive evidence. Long-term monitoring revealed substantial improvements in bone density and microarchitecture, underscoring the importance of early diagnosis and intervention for genetic causes of osteoporosis to prevent fracture-related morbidity.

01 May 2025·American Journal of Medical Genetics Part A

Hajdu–Cheney Syndrome, a Rare Cause of Acro‐Osteolysis and Osteoporosis With Zoledronic Acid Experience

Article

Author: Buyukyilmaz, Gonul ; Adiguzel, Mehmet ; Gurbuz, Fatih ; Kılıc, Esra

ABSTRACTHajdu–Cheney syndrome (HCS), caused by a heterozygous gain of function variant of the NOTCH2 gene, is a rare skeletal dysplasia. Although the main presentation is acro‐osteolysis, osteoporosis, and facial dysmorphism, having a wide range of clinical manifestations creates diagnostic difficulties. Here, a 15‐year‐old male patient with HCS who had no complaints until this age except for two short bone fractures and one vertebral collapse fracture due to a fall was reported. The patient presented with acro‐osteolysis, facial anomalies, skull deformity, and osteoporosis. The clinical diagnosis of HCS was supported by a positive genetic test of a novel de novo heterozygous pathogenic variant in exon 34 of NOTCH2 c.6614dupAfs*. Zoledronic acid treatment was applied for 2 years, and the patient responded well to the treatment, showing signs of improved bone density and improvement in vertebral height. We identified a novel NOTCH2 gene variant related to HCS. Our findings could extend phenotypic spectrum and genotype–phenotype correlations. The results of this case report support that antiresorptive treatment with zoledronic acid increased bone mineral density. Nevertheless, because of the low prevalence of the syndrome and the small number of reported cases, further studies are required to understand the syndrome better and establish treatment guidelines.

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Hypotonia-Cystinuria Syndrome

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