Table 1.

Pathological, clinical, and diagnostic features of inborn errors of purines.

Enzyme (Name; Symbol; EC)	Gene (Symbol; Location; Omim Code)	Pathology (and Variants)	Clinical Features	Diagnostics
Phosphoribosylpyrophosphate Synthetase; PRPS1; EC 2.7.6.1	PRPS1; Xq22.3; OMIM 311850	PRPS superactivity	Stones; gout Sensorineural deafness Neuromotor retardation	Hyperuricemia and/or hyperuricuria High PRPS activity in red cells and fibroblasts High PRPP levels; low GTP and NAD levels in red cell Genetic analysis
		PRPS deficiency(DFNX1; CMTX5; Arts syndrome)	Hearing impairment Neuromotor retardation Optic atrophy	Normal serum UA Low to absent PRPS activity in red cells and fibroblasts Genetic analysis
Hypoxanthine-Guanine Phosphoribosyltyransferase; HPRT; EC 2.4.2.8	HPRT; Xq26.2-q26.3; OMIM 308000	Lesch–Nyhan Disease (total deficiency)Lesch–Nyhan variants (partial deficiency)	Gouty arthritis Neurobehavioral disturbance Lithiasis Megaloblastic anemia	Hyperuricemia and/or hyperuricuria Absent to very low HPRT activity in red cells, lymphocytes, or fibroblasts Genetic analysis
Adenylosuccinate lyase; ADSL; EC 4.3.2.2	ADSL; 22q13.1; OMIM 608222	ADSL deficiency S-Ado/SAICAr < 1 in fatal neonatal form S-Ado/SAICAr = 1 in severe type I S-Ado/SAICAr >1 in moderate type II	Fatal neonatal form: hypokinesia, intractable seizures, and respiratory failure Severe type I form: severe psychomotor retardation, microcephaly, seizures, autistic features Moderate type II form: moderate or slight psychomotor retardation	High levels of SAICAr and S-Ado in urine, plasma, and CSF Low ADSL activity (>2%) in fibroblasts Genetic analysis
Inosine-5′-monophosphate dehydrogenase IMPDH; EC 1.1.1.205	IMPDH1; 7q32.1; OMIM 146690	IMPDH1 malfunction: Retinitis pigmentosa type 10 Leber congenital amaurosis type 11	Retinal degeneration Night blindness Loss of peripheral visual field	Genetic analysis
	IMPDH2; 3p21.31; OMIM 146691	IMPDH2 deficiency: Severe juvenile neuropathies	Dystonia Tremor	Genetic analysis
Ectosolic 5′-nucleotidase; eN; EC 3.1.3.5	NT5E; 6q14.3; OMIM 129190	eN hyperactivity: Nucleotidase-associated pervasive developmental disorder (NAPDD)	Hyperactivity, impulsiveness, aggressiveness Poor attention span and social interaction Neurological symptoms: seizure ataxia, impaired fine motor control	eN activity in fibroblasts Hypouricuria
		eN deficiency: Calcification of joints and arteries (CALJA)	Calcification of joints and arteries	Genetic analysis
Cytosolic 5′-nucleotidase; cN-II; EC 3.1.3.5	NT5C2; 10q24.32-q24.33; OMIM 600417	Hereditary spastic paraplegia type 45 (HSP-cN-II deficiency)	Loss of corticospinal motor tract function Progressive limb spasticity and weakness	Genetic analysis
Adenosine monophosphate deaminase; AMPD; EC 3.5.4.6	AMPD1; 1p13.2; OMIM 102770	Myoadenylate deaminase deficiency (AMPD1)	Exercise induced early fatigue, cramps, and myalgia Hypersomnia	Low AMDP1 activity in skeletal muscles AMDP immunohistochemistry in muscle biopsy Genetic analysis
	AMPD2; 1p13.3; OMIM 102771	Pontocerebellar hypoplasia type 9 (AMPD2 deficiency)	Microcephaly Hypoplastic/absent corpus callosum Severe intellectual disability	Low AMPD2 activity Low AMPD2 levels Genetic analysis
Adenosine kinase; ADK; EC 2.7.1.20	ADK; 10q22.2; OMIM 102750	ADK deficiency	Liver dysfunction Delayed psychomotor development Mild dysmorphic features Hypotonia and epilepsy Vascular abnormalities	Hypermethioninemia High levels of S-adenosylmethionine and S-adenosylhomocysteine Genetic analysis
Adenosine deaminase; ADA; EC 3.5.4.4	ADA1; 20q13.12; OMIM 608958	Severe combined immunodeficiency (SCID-ADA1 deficiency)	Lymphocytopenia Recurrent infections Neurodevelopmental deficits Sensorial deafness Skeletal abnormalities	High levels of dAdo, dATP, total dAdo nucleotides Absent to extremely low ADA1 activity. Genetic analysis
	ADA2; 22q11.1; OMIM 607575	ADA2 deficiency	Autoinflammatory, vasculopatic, hematologic and immune system dysfunction Neurological manifestations (dysartria, ataxia, palsy) Cognitive impairment Neuropathy (central and peripheral) Intracerebral haemorrhaging and aneurysm Immunodeficiency	Absent to low ADA2 activity in plasma and serum Genetic analysis
S-Adenosylhomocysteine hydrolase; SAHH; EC 3.3.1.1	AHCY; 20q11.22; OMIM 180960	SAHH deficiency	Developmental delay Hypotonia Cerebral hypomyelination, coagulation abnormalities and hepatopathy (variable) Microcephaly, strabismus and behavioral changes (frequent)	High levels of SAH and SAM in plasma Hypermethioninemia Normal homocysteinemia Increased activity of creatine kinase Genetic analysis
Purine nucleoside phosphorylase; PNP; EC 2.4.2.1	PNP; 14q11.2; OMIM 164050	PNP deficiency (SCID)	T-cell immunodeficiency Neurological symptoms Recurrent infections Autoimmuny (idiopathic thrombocytopenic purpura, thyroiditis, SLE) Developmental delay	Hypouricemia and/or hypouricuria High levels of inosine, guanosine (and their deoxy forms) in urine and plasma Low PNP activity in red cells Genetic analysis