Table 4.

Suggested updated criteria for initiation of Gaucher disease-specific treatment.

Israeli Ministry of Health Criteria for Imiglucerase, 1998 [28]	Suggested Updated Criteria for ERT/SRT
A family history in a sibling with a rapid acceleration in the course of the disease.	When symptomatic or high lyso-Gb1 *
Age of onset of signs or symptoms of the disease below 5 years of age	Age is not a criterion by itself
At any age, enlargement of the spleen and liver is accompanied by signs of hypersplenism, abnormal liver function tests, or other complications	Stays as is
Hypersplenism expressed as serious pancytopenia: hemoglobin below 9 g%, white count below 3000/mm3, platelet count of 50 000/mm3 or less, in consecutive blood tests during a three-month approximated	Gaucher-related significant, symptomatic cytopenia and/or bleeding disorder, irrespective of lyso-Gb1 levels
Symptomatic anemia which is not the result of iron deficiency or due to other causes unrelated to Gaucher disease, or thrombocytopenia with a tendency to bleeding, or a consistently decreasing platelet count.	Redundant
Signs of an autoimmune mechanism which are persistent or increasing during a follow-up period of a few years.	With high lyso-Gb1
Bone involvement expressed as recurrent or acute crises of pain, with objective documentation (e.g. MRI, bone scan, X-ray, or the expert opinion of a rheumatologist or orthopedist), spinal compression or evidence of other serious changes on X-ray even in the absence of pain.	Bone pain or evidence of significant bone involvement in MRI/ DEXA or any imaging abnormalities and the presence of high lyso-Gb1
Lung involvement	Stay as is
Evidence of decreased height or weight accompanied by a clinical picture of malnutrition.	Short stature after exclusion of other causes or with the presence of high lyso-Gb1
Molecular diagnosis of a ‘severe’ genotype (other logical parameters and of the reduction in organ- than homozygosity for N370S (1226G)) in the presence of signs or symptoms which may be milder than those stated above; however, this criterion does not include asymptomatic patients.	Molecular diagnosis of a ‘severe’ genotype ** and high lyso-Gb1
-	Any patient who was diagnosed with malignancy requiring myelosuppressive therapy

* High lyso-Gb1 in our cohort would be lyso-Gb1 > 250 ng/mL based on measurements performed in Centogene on DBS. However, we use the term “high lyso-Gb1” (a several-fold increase from the diagnostic lyso-Gb1 cutoff) to reflect the variability in methodology and unit of lyso-Gb1 measurements between laboratories. ** non N370S (c.1226A > G) homozygous or N370S/R496H (c.1604G) compound heterozygous.ERT, enzyme replacement therapy; SRT, substrate reduction therapy; MRI, magnetic resonance imaging; DEXA, dual-energy X-ray absorptiometry.