ABSTRACT
Ornithine transcarbamylase (OTC) deficiency (OTCD) is an X-linked urea cycle disorder. In females - undergoing random X chromosomal inactivation (XCI) - disease severity depends on the XCI pattern. Hence, female OTCD subjects with favorable XCI display normal OTC expression and activity and are healthy carriers. Whereas females undergoing less favorable XCI may suffer from severe and fatal OTCD. In approximately 20% of patients with biochemical evidence of OTCD, no mutation can be identified hampering definitive diagnosis and adequate treatment.Here, we describe a female patient with high suspicion of OTCD in whom molecular genetic work-up did not reveal pathogenic variants in the OTC gene. In her case, this was particularly challenging, since she was awaiting liver transplantation due to metabolic instability. In order to substantiate the suspected diagnosis of OTCD, we applied our previously reported in vitro OTCD liver disease model. Patient-derived skin fibroblasts were reprogrammed into human induced pluripotent stem cells (hiPSCs) followed by differentiation into hepatocytes (hiPSC-Heps). Among five randomly selected hiPSC clones - differentiated into hiPSC-Heps - one clone expressed OTC protein, while the four remaining clones lacked OTC expression, supporting the patient's suspected diagnosis of OTCD.To conclude, we demonstrate that hiPSC technology is a powerful diagnostic tool to substantiate the suspected diagnosis of OTCD in patients lacking genetic confirmation. Furthermore, selecting clones that exclusively express the wild-type OTC protein, could be used strategically as cellular therapy in future. Ultimately, this approach might be applicable to virtually any X-linked disease. Synopsis: Induced pluripotent stem cell technology is a powerful diagnostic tool to substantiate the suspected diagnosis of OTCD in patients lacking genetic confirmation.
ABSTRACT
Índralupta is a disease characterized by patches of hair loss spread throughout the body and scalp. It can be considered alopecia areata according to conventional medical care. The present case report is on the effectiveness of shodhana (treatment in which aggravated doshas are expelled from the body) and shamana (treatment that pacifies the aggravated doshas) in the patient of índralupta. A patient 25 years old, had hair loss patches on the scalp and many other areas of the body. The patient took conventional modern medicine as well as ayurveda treatment but didn't get a satisfactory result. The patient was hospitalized and treated with vamana (medicated emesis), virechana (medicated purgation), basti (administration of medicine through procto-colonic route), raktamokshana (blood-letting), and nasya (medicine administered through nasal route) along with shamana treatment for more than 6 weeks. The hair eruption started from many patches of the scalp and whole body. In this case, regrowth of hair from hair follicles was evident within 15 days of treatment. The collected data of this study suggest that shodhana and shamana treatment can provide noteworthy relief in índralupta.
