Table 3.
Key monitoring parameters and frequency of assessment for patients with ASMD type B forms (NPD B).
| Test | Monitoring Frequency | Additional Points |
|---|---|---|
| Lung assessment | ||
| PFT | PFT possible in children from 5–6 years Need to monitor DLco (annually or at clinician’s discretion) following olipudase alfa treatment initiation |
|
| Blood gases | - | Non-predictive test Not routinely recommended, especially in children, and depending on symptomatology in adults |
| CT scan | At baseline visit and at follow-up visit annually, unless normal (then assess every 5 years) | Radiation examination in a population at risk of cancer In paediatric patients <4–5 years, sedation or general anaesthesia is required (depending on the child’s behaviour) |
|
Hepato-splenic
assessment |
||
| Liver blood tests | At baseline visit, at follow-up visit in first 6 months, and at follow-up visit annually | Assess GGT, transaminases, ALP, bilirubin, PT, CRP, Factor V |
| Abdominal ultrasound with doppler | At baseline visit, at follow-up visit in first 6 months, and at follow-up visit annually | Early detection of steatosis, PHT, cirrhosis or nodule Possible in children < 5 years of age |
| Abdominal MRI (adult patients) | At initial assessment and then every 2 years | Higher sensitivity for nodule detection Possible in children > 5 years of age |
| Fibroscan | - | Not recommended as not validated for ASMD |
| Liver biopsy | To consider if hepatocarcinoma is suspected | No correlation with biological tests (transaminases usually < 5 N). Characterisation of nodule may require alpha-foetoprotein, liver ultrasound, and MRI |
| Alpha-fetoprotein | - | No recommendation for systematic assessment |
|
Haematological
assessment |
||
| CBC, platelets, haemostasis test (PT, Factor V, fibrin, aPTT), ferritin | Assessment at baseline visit, at follow-up visit every 3 months during first year, and at follow-up visit annually | - |
| Protein electrophoresis | At initial assessment and then annually | Risk of hyper or hypogammaglobulinemia and risk of MGUS No need to perform any immunoelectrophoresis |
| Serum albumin | At initial assessment then every 2–3 years if the initial assay is normal | - |
| Bone assessment and growth evaluation | ||
| Growth curve | Assessment at baseline visit and at follow-up visit every 6 months | - |
| Phosphocalcium balance | Assessment at baseline visit and at follow-up visit every 6 months | Assessment to include blood calcium and phosphorus, vitamin D, creatinine, proteinuria, urine calcium and sodium, and creatininuria Patients are at risk of cholestasis |
| Absorptiometry | Assessment at baseline visit and then every 5 years if normal or every 3 years if anormal | Possible in children aged from 5–6 years old |
| Resorption markers | Optional | To be performed if osteoporosis is known |
| Cardiovascular assessment and lipid profile | ||
| Echocardiography | At initial assessment and then every 2 years | |
| Coronary computed tomographic angiography | Discuss coronary computed tomographic angiography depending on lipid profile and other cardiovascular risk factors | No monitoring data in ASMD type B disease |
| Lipid profile | Assessment at baseline visit, at follow-up visit every 3 months during first year, and at follow-up visit annually | Unproven benefit of statins in primary prevention |
| Neurological assessment a | ||
| Peripheral | ||
| Clinical examination | Monitoring frequency: at initial assessment and then annually | |
| EMG | Monitoring frequency: to be considered if there are clinical call points | |
| Central nervous system | ||
| Brain MRI | Monitoring frequency in adults: to be considered at initial assessment according to the clinical context and the neuropsychological tests Monitoring frequency in children: to be carried out at initial assessment if the diagnosis is made at a very early stage of childhood |
|
| Ophthalmic assessment | ||
| Ocular fundus | At initial assessment | The macular cherry-red spot is present in all patients with form A, and has been reported in one third of patients with form B [20] |
| Visual acuity | At initial assessment | Loss of visual acuity in infantile type (no effect in chronic visceral ASMD) |
| Other | ||
| Dermatological examination | At initial assessment and then annually | Necessary in order to assess the presence of lymphoedema (eyelid infiltration) |
| TSH assay (in combination with anti-TPO antibodies) | At initial assessment and then annually | Necessary for the investigation of thyroid autoimmunity |
| Biomarkers | ||
| Chitotriosidase | At initial assessment, follow-up every 3 months for the first year, and then every year | Chitotriosidase activity is absent in 6–8% of individuals in the general population |
| Specialised assays, contact reference laboratories | ||
| Lysosphingomyelin + Lysosphingomyelin isoform 509 |
At initial assessment, follow-up every 3 months for the first year, and then every year | Specialised assays, contact reference laboratories |
a Note: The clinical dichotomy between forms A and B occurs very early before the age of 1 year (around 3–6 months). For form A/B, the age of onset of neurological signs is highly variable (delayed acquisition at a variable age, possible after the age of 3 years). aPTT, activated partial thromboplastin time; CBC, complete blood count; CRP, C-reactive protein; CT, computerised tomography; DLco, diffusing capacity of the lungs for carbon monoxide; EMG, electromyography; GGT, gamma-glutamyl transferase; MGUS, monoclonal gammopathy of unknown significance; MRI, magnetic resonance imaging; PFT, pulmonary function test; PHT, portal hypertension; PT, prothrombin time; TSH, thyroid-stimulating hormone; TPO, thyroid peroxidase.