Table 2.

Classification of exceptionally rare diseases included in the present study according to Orphanet

General classification	Total (N = 166)	Disease group classification	Total
Metabolic disease involving complex molecules	62	Lysosomal diseases	31 (50%)
		Purine or pyrimidine metabolism disorder	10 (16%)
		Sterol metabolism disorder	8 (13%)
		Metabolic neurotransmission anomaly	5 (8%)
		Peroxisomal disease	4 (6%)
		Metal transport or utilisation disorder	3 (5%)
		Protein glycosylation disorder	1 (2%)
Metabolic intoxication disease	36	Amino or protein metabolism disorder	34 (94%)
		Hyperoxaluria	1 (3%)
		Methylmalonic aciduria - microcephaly - cataract	1 (3%)
Energy metabolism disorder	45	Mitochondrial disorder	26 (58%)
		Fatty acid oxidation or ketogenesis disorder	7 (9%)
		Creatine biosynthesis disorder	2 (4%)
		Ketolysis disorder	2 (4%)
		Enolase deficiency	1 (2%)
		Gluconeogenesis disorder	1 (2%)
		Hemolytic anemia due to glucophosphate isomerase deficiency	1 (2%)
		Phosphoglycerate kinase 1 deficiency	1 (2%)
		Pyruvate metabolism disorder	1 (2%)
		Thiamine-responsive megaloblastic anemia syndrome	1 (2%)
		Tricarboxylic acid cycle disorder	1 (2%)
		Triose phosphate-isomerase deficiency	1 (2%)
Carbohydrate metabolism disorder	12	Glycogen storage disease	7 (58%)
		Glucose transport disorder	4 (33%)
		Familial hyperinsulinism	1 (8%)
Other metabolic disease	11	Metabolic disease associated with a progressive neurological disorder	6 (55%)
		Miscellanous metabolic disease with mostly hepatic presentation	4 (36%)
		Hereditary hypercarotenemia and vitamin A deficiency	1 (9%)