Cystinosis
Description
● OVERVIEW:
➣ Cystinosis is a rare autosomal recessive metabolic illness.
➣ Contributing factors include mutations in the CTNS gene, a malfunctioning lysosomal cystine transporter, cystine buildup, and damage to several systems, including the kidneys, eyes, endocrine system, heart, and nerves.
➣ Mostly from Europe and the USA, incidence ranges from 1:260,000 to 1:115,000; there is little data from China.
➣ Particularly uncommon paediatric instances in China result in low awareness and delayed diagnosis.
➣ Prognosis is improved and ESRD is postponed with early diagnosis and therapy.
● Talk about epidemiology
➣ Rare in Asia: 1 case
→ Japan, 6 cases
→ Thailand, and 2 cases → India.
→China: around 21 instances (including Taiwan and the mainland).
• N323K, c.681G>A, c.477C>G, c.274C>T, c.680A>T, IVS6+1delG, IVS8-1delGT, 18_21del GACT, 57kb deletion, and other Chinese mutations have been described.
• In this instance, the c.140+5G>A mutation in intron 4 was reported for the first time.
➣ Clinical variants include growth retardation and infantile (nephropathic) CKD, which is the most severe kind with an early start.
• Juvenile/intermediate → slower progression, later onset.
Mostly corneal crystals, ocular non-nephropathic.
• Current patient: infantile type, involving multiple systems (thyroid, kidney, and bone).
➣Methods of diagnosis:
• Leukocyte cystine levels (gold standard, sensitive, therapy monitoring).
• CTNS sequencing, or genetic testing, is accurate but expensive.
•Slit-lamp for corneal crystals: inexpensive, precise, but not very useful for treatment or early monitoring.
➣ The difficulties in this instance
• Five years pass between the initial manifestation and the genetic diagnosis.
• Poor compliance as a result of geographical, cultural, and economical limitations.
• Cysteine is unavailable in China; supportive care is the sole option.
● Case Presentation: 9-year-old girl from Sichuan, China, of Zang ethnicity
➣ Early history:
• Normal pregnancy and delivery with non-consanguineous parents.
• Normal milestones at first → unable to stand or walk by age 3.
• At age 4, Fanconi syndrome (growth retardation, anaemia, hypophosphatemia, vitamin D insufficiency, and RTA) was diagnosed.
Phosphate, citrate, calcium, and vitamin D were used as treatments.
• Poor adherence to therapy as a result of social and cultural circumstances, as well as the family's limited knowledge and availability.
➣ Development (8–9 years)
• Accumulated agony, claw-like hand deformities, and exhaustion.
• Symptoms worsened after stopping drugs.
• Displayed bone abnormalities (X-legs, chicken chest, rickets), as well as growth failure (weight 18 kg, height 108 cm, <3rd percentile).
• Biochemistry: normocytic anaemia, metabolic acidosis, hypophosphatemia, hypocalcaemia, hypokalaemia, ↑ PTH, ↑ ALP.
• Renal function: eGFR 20.17 → CKD stage IV, creatinine ↑ 163 μmol/L, and BUN ↑ 6.98 mmol/L.
Urinalysis: tubular proteinuria, proteinuria, and glycosuria → proximal tubulopathy.
• Imaging: bone densitometry: low BMD, osteoporosis; renal ultrasound: elevated parenchymal echogenicity.
Tetany (hypocalcaemia), mesenteric lymphadenitis, and secondary hyperparathyroidism are complications.
• No corneal crystals in ophthalmology.
➣ The whole exome sequencing (WES) revealed a new homozygous CTNS mutation c.140+5G>A (intron 4) in the field of genetics.
• New mutation, pathogenic, not included in major databases.
• Genetic testing was refused by the family, so inheritance was not verified.
Iron, phosphate, calcium, vitamin D, and lysine are examples of supportive treatment.
• Citrate ceased (hypocalcaemia worsened).
• Low protein diet.
• Suggested strict monitoring and dialysis preparation → family non-compliance once more.
Protocol
➣ Therapy: In industrialised nations, cysteamine (mercaptamine bitartrate) is the conventional treatment.
→ Mechanism: lessens the buildup of lysosomal cystines.
→Benefits include enhancing growth, delaying ESRD, and extending life.
→Limitations include frequent doses, adverse effects, and the inability to treat illness.
→ Compliance is enhanced with delayed-release cysteamine.
Phosphate, citrate, vitamin D, calcium, growth hormone, and thyroid replacement are all supportive.
•Advanced: kidney transplantation and dialysis (not curative; systemic cystinosis persists).
• Future: gene editing (CRISPR, CTNS correction), stem cell transplantation.
●The main issues encountered
➣The youngster suffered from a variety of illnesses brought on by mutations in the CTNS gene, which causes cystinosis, a rare lysosomal storage disorder:
➣Motor Development Delay: By the age of three, the patient was unable to stand or walk and had aberrant bone abnormalities, including claw-like hands, "X" legs, and chest distortion.
➣Renal Involvement (Fanconi Syndrome and Chronic Kidney Disease): The girl began with metabolic acidosis, electrolyte abnormalities, proteinuria, glucosuria, and eventually advanced to stage IV of chronic kidney disease.
➣Recurrent tetany and bone pain are caused by metabolic and electrolyte disturbances, which include hypokalaemia, hypocalcaemia, hypophosphatemia, and secondary hyperparathyroidism.
➣ Malnutrition and Growth Retardation: Vitamin D insufficiency, thin subcutaneous fat, and stature and weight continuously below the third percentile.
➣ Poor Treatment Compliance: Infrequent medication adherence and medical follow-up because to a variety of issues, including sociocultural factors, family views, and restricted availability.
psychological Issues: The psychological well-being of the patient and their family was influenced by physical limits, chronic sickness, and repeated hospitalisations.
●Nursing Management and Interventions
➢Evaluation and Observation
• Comprehensive Health Assessment: To track the course of the condition, routine anthropometric measures, thorough recording of dysplasia, neurological evaluations, and assessments of bone deformities and discomfort were carried out.
• Laboratory Monitoring: Constant monitoring of haemoglobin (for anaemia), renal function (creatinine, urea), electrolyte levels (Ca, K, phosphorus), and indicators of bone metabolism (vitamin D, parathyroid hormone, alkaline phosphatase).
• Monitoring Medication Effects: Consistent evaluation of the efficacy and side effects of medications, particularly when taking calcium, phosphate, and vitamin D supplements and following intravenous treatment for acute symptoms.
➣ Direct Management of Symptoms
• Electrolyte Repletion: For tetany and hypocalcaemia, acute therapy involved oral and intravenous calcium, stopping citrate (which binds calcium), and taking potassium and phosphate supplements orally.
• Correction of Metabolic Acidosis: To treat acidosis, medications such as potassium and sodium citrate combinations were administered.
• Vitamin D and Calcium Supplementation: To maintain bone health and treat chronic hypocalcaemia, oral and intravenous vitamin D/calcium supplements were given; calcitriol was used to treat deficiencies.
• Pain and Deformity Management: Orthopaedic therapies (such as a pectus carinatum brace for chest deformity), physical therapy, and analgesics were administered.
➣ Particular Techniques to Increase Compliance
• Sustained-release Formulations: Although the medication is not currently accessible in China, details on novel cysteamine delayed-release formulations that lessen pill load and enhance adherence were given.
•Case-Based Counselling: The dire repercussions of non-compliance and drug withdrawal were demonstrated using actual case studies.
• Technology Use: Telehealth and follow-up networks facilitated communication, removing access and geographic constraints.
➣ Chronic Illness and Therapy Adherence
•information and Family Support: Nurses gave patients individualised health information about cystinosis, the value of taking medications as prescribed, and how to manage the illness at home.
• Follow-Up and Reminders: To guarantee adherence to routine urine and kidney function evaluations, families received coaching through network-based follow-up.
• Psychosocial Support: In an effort to enhance the patient's and her family's quality of life, nursing staff addressed sociocultural and practical obstacles to compliance, such as family beliefs, comprehension of chronic disease, and the requirement for constant care.
• Dietary Management: To promote development and delay the course of kidney impairment, education was emphasised on limiting high-protein consumption and making sure one is getting enough nutrients.
•Preparation for Advanced Care: Nurses advised the family of pre-dialysis care logistics, including setting up central venous access, as the patient neared end-stage renal disease.
Notes
For more details visit 10.3389/fped.2022.860990
