Metabolic and Enzyme Deficiency Diseases (Table 2-9)
| | | | | | | Table 2-9 Metabolic and Enzyme Deficiency Diseases | | | Disease | | Inh | | Defect | | Clinical Findings | | | Alkaptonuria | | AR | | Homogentisic acid (HA) oxidase | | Blue-gray pigmentation of cartilage (helices), sclera and skin (axilla); urine darkens on standing, arthritis | | | Biotinidase
Deficiency | | AR | | | | Alopecia, periorificial dermatitis, developmental delay, seizures; treat with biotin | | | Fabry Disease | | XLR | | α-Galactosidase A | | Glycosphingolipids in vascular endothelium: multiple angiokeratomas, extremity pain/paresthesias, whorl-like corneal and lenticular opacities, birefringent lipid globules in urine (“maltese crosses”), MI, cerebrovascular accident (CVA) | | | Fabry Disease | | AR | | α-Fucosidase | | Multiple angiokeratomas, coarse facies, growth retardation, dysostosis multiplex, mental retardation | | | Gaucher Disease | | AR | | α-Glucosidase
(Glucocerebrosidase) | | Type I (adult): no CNS findings + diffuse brown skin pigmentation, thrombocytopenia, hepatosplenomegaly (HSM), bone pain, ehrlenmeyer flask deformity of femoral midshaft | | | | | | | | | Type 2 (infant): no skin findings, severe, rapid death | | | | | | | | | Type 3 (juvenile): chronic neuropathy | | | Hartnup Disease | | AR | | SLC6A19 | | ↓ Renal reabsorption of neutral amino acids, pellagra-like dermatosis with photosensitivity, ataxia, tremors | | | Holocarboxylase
Synthetase
Deficiency | | AR | | | | Alopecia, perioral/perianal dermatitis, metabolic encephalopathy, metabolic acidosis; treat with biotin | | | Hunter Disease | | XLR | | Iduronidate sulfatase | | Firm, flesh-colored to white papules coalescing over scapula | | | Hurler Disease | | AR | | α-L-iduronidase | | Mental retardation (MR), HSM, hernia, opacities, gargoyle-like features | | | Lesch–Nyhan
Syndrome | | XLR | | HGPRT deficiency | | Self-mutilation, orange crystals in the diaper, gout, choreoathetosis, MR | | | Lipoid Proteinosis | | AR | | ECM1 defect | | Pearly papules, hippocampal calcification, infiltration of deposits on lips and tongue (wooden), hoarseness | | | Neimann–Pick
Disease | | AR | | Sphingomyelinase
deficiency (SMPD1) | | Type A: failure to thrive, HSM, neurologic deterioration
Type B: minimal neurologic disease, xanthomas, histiocytic infiltration in viscera, psychomotor delay, muscle weakness, blindness (cherry red spots) | | | Phenylketonuria | | AR | | SLC39A4
(zinc transporter) | | Diffuse hypopigmentation, eczema, MR, sclerodermoid changes, blonde hair, blue eyes, urine and skin with mousy odor | | | Prolidase
Deficiency | | AR | | Prolidase | | Skin fragility, ulceration and scarring over lower extremities, photosensitivity, MR, recurrent infections | | | Wilson’s Disease | | AR | | ATP 7B (ATPase copper transporting enzyme) | | Copper accumulation in liver/brain/cornea, cirrhosis, blue lunula, Kayser–Fleischer rings, ataxia, dementia, hepatomegaly | | | | | | | | | |
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