Cystinosis – The Post-transplant Era
Exocrine pancreatic insufficiency leads to malabsorption, with a coefficient of fat absorption of about 60% (normal >90%).30 Inflammatory bowel disease and fatal bowel perforation due to chronic intestinal damage have been reported in patients with severe cystinosis.59
Endocrine
Clinical and biochemical hypothyroidism continues as cystinosis patients progress into older age. Diabetes due to pancreatic endocrine insufficiency is a fairly frequent long-tem complication of NC, requiring insulin therapy by 20 years of age in about 25%.60 Cystine deposits have been detected in islet cells of patients post
mortem.30
Unlike type 1 diabetes , glucose intolerance in patients
with infantile cystinosis is characterised by a slowly progressive loss of insulin secretion and C-peptide production.61
Other factors
such as glucocorticoids or cyclosporine may contribute to the progressive endocrine pancreatic insufficiency. Long-term therapy with cystine-depleting agents may reduce involvement of the endocrine pancreas.
Females show no signs of gonadal dysfunction, and have normal ovulatory cycles. Perhaps five to 10 women with cystinosis have delivered healthy babies post-transplant. However, males exhibit a high incidence of hypogonadism, loss of testicular volumes and reproductive impairment; histological findings include cystine accumulation, germinal dysplasia and Leydig cell hyperplasia.62 impaired in cystinosis,63
Sweating and tearing are with mild clinical repercussions.
Pulmonary
Significant pulmonary dysfunction presents as extraparenchymal restrictive lung disease in adults with cystinosis, particularly in patients who have not received long-term cysteamine therapy. The lung dysfunction appears related to extrinsic muscle impairment rather than to a primary parenchymal defect.1
Pulmonary function
tests show decreased lung volumes with reduced maximal inspiratory pressure, maximal expiratory pressure and maximal voluntary ventilation and normal diffusing capacities.1
Open lung biopsy in a
patient with a severe restrictive defect demonstrated pulmonary fibrosis with cystine crystals.1
Treatment of the cystinosis myopathy
with cysteamine can be expected to prevent the restrictive pulmonary disease.
containing cystine crystals70 (see Figure 3B). Hypersplenism has been
Cardiovascular
Renin-dependent hypertension is well documented in NC patients and generally continues one to three years post-transplant.64
Some
patients have hypercholesterolaemia and some develop vascular calcifications due to continued intracellular storage of cystine, destruction of vascular endothelial cells and atherosclerosis;65 contributes to cardiovascular morbidity.66
this There are reports of patients
with cardiomyopathy in whom post mortem examinations showed cystine crystals within interstitial histiocytes in the myocardium.67 dissecting aortic aneurysm has also been reported.67
A The effects of
long-standing renal failure and hypertension on the myocardium and coronary vessels can include coronary artery dilatation.68
Haematological
In cystinosis, cystine accumulates within platelets, so patients could theoretically be at increased risk for bleeding;69
Neurological
Central nervous system deficits, which occur in perhaps 5–10% of adults not treated with cysteamine, are heterogeneous in nature and include hemiparesis, pyramidal and extrapyramidal dysfunction, hydrocephalus,
progressive dementia. Cystine crystals are present in the choroid plexus, perivascular spaces, dura and meninges, but not in the glial cells of patients with cerebral atrophy.3,30
Encephalopathy, sometimes
leading to a ‘pseudobulbar state’, can be pronounced in patients with cerebral atrophy or metabolic brain dysfunction.72
Psychometric
defects are rare and localised to visuospatial processing deficits; cognitive impairment specifically affects the spatial domain.73
Many we have not seen a
case of this. Some patients have marked anaemia, possibly due to bone marrow involvement; bone marrow biopsies reveal macrophages
EUROPEAN NEPHROLOGY
patients have memory loss and are at increased risk of seizures and stroke-like episodes.24
Intracranial hypertension and non-absorptive hydrocephalus can develop, possibly due to defective reabsorption
59
reported in a few patients, with associated thrombocytopenia and severe anaemia.71
Figure 5: Swallowing Severity Score as a Function of Time without Cysteamine Treatment (A) and Duration Receiving Cysteamine (B)
A
4.5 4
3.5 3
2.5 2
1.5
0.5 1
0 0 5
10 15 20 25 30 35 40 Years without cysteamine
B
4.5 4
3.5 3
2.5 2
1.5
0.5 1
0 0 5 10 15 Years with cysteamine
The swallowing severity score reflected increasing degrees of dysfunction. On this scale, a rating of 1 indicates a normal bolus flow and duration, a rating of 2 reflects a mild impairment of bolus flow, a score of 3 indicates a moderate impairment of bolus flow with pharyngeal stasis and/or laryngeal penetration and a score of 4 indicates severe dysphagia with aspiration on more than one bolus consistency and/or a swallow duration longer than five seconds. Swallowing dysfunction increased with years off cysteamine and decreased with years on cysteamine. Source: Nesterova and Gahl, 2008,19 Business media.
with kind permission from Springer Science +
20 25 45
personality and cognitive impairments and
Swallowing score
Swallowing score
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