Internal Medicine

0521779407-17 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:19

Purine and Pyrimidine Disorders 1253

➣Adenosine deaminase (ADA) deficiency: severe combined

immunodeficiency (SCID), persistent diarrhea, pulmonary dis-

ease, moniliasis, absent lymph nodes, hepatic dysfunction

➣Purine nucleoside phosphorylase (PNP) deficiency: recurrent

infections (T-cell immunodeficiency), SCID (accounts for∼4%

of SCID patients), 2/3 have neurologic dysfunction (hypotonia,

cerebral palsy), 1/3 have autoimmune disease (hemolytic ane-

mia, idiopathic thrombocytopenic purpura, systemic lupus ery-

thematosus)

■Pyrimidine disorders

➣Hereditary orotic aciduria (uridine monophosphate synthetase

[UMPS] deficiency): crystalluria, pallor (megaloblastic anemia),

failure to thrive

➣Uridine monophosphate hydrolase (UMPH1) deficiency

(pyrimidine-5’-nucleotidase deficiency): splenomegaly, pallor

(hemolytic anemia)

➣Dihydropyrimidine dehydrogenase (DHPD) deficiency: asymp-

tomatic, seizures, developmental delay, severe toxicity to 5-

fluorouracil

➣Dihydropyrimidinase (DHPA) deficiency: asymptomatic, seiz-

ures, developmental delay

➣Ureidopropionase deficiency: hypotonia, developmental delay,

dystonia, optic atrophy, scoliosis

tests

Laboratory

■basic blood studies:

➣anemia (UMPS, UMPH1 deficiencies)

➣increased BUN, creatinine (HPRT, APRT, XDH deficiencies, PRPS

superactivity)

➣increased uric acid (HPRT deficiency, PRPS superactivity)

➣decreased uric acid (XDH, PNP deficiencies)

➣decreased immunoglobulins (ADA deficiency)

■basic urine studies:

➣crystalluria (HPRT, APRT, UMPS defs.)

➣increased uric acid (HPRT deficiency, PRPS superactivity)

Screening

■increased urine orotic acid (UMPS def.)

■decreased CD4+cells (ADA def.,±PNP def.)

■decreased CD8+cells (ADA def.)