Summary of hepatic and renal anomalies associated with inherited metabolic disorders
| Metabolic condition | Deficient enzyme | Renal abnormalities | Hepatic abnormalities | Associated features | Biochemical pathway involved |
|---|---|---|---|---|---|
| DHCR7, 7-dehydrocholesterol reductase; CPT II, carnitine palmitoyl transferase type II; ETF, electron transfer flavoprotein; ETF-QO, ETF ubiquinone oxidoreductase; NALD, neonatal adrenoleucodystrophy; IRD, infantile Refsum’s disease; RCDP, rhizomelic chondrodysplasia punctata; HPA, hyperpipecolic aciduria; PMM2, phosphomannomutase. | |||||
| Smith-Lemli-Opitz syndrome | DHCR7 | Renal hypoplasia and aplasia, renal cortical cysts, ectopia and hydronephrosis | Abnormal bile acids, iron deposits, cholestasis, dysplasia, and hypoplasia of the gallbladder | Skeletal malformations, including polydactyly and syndactyly, craniofacial defects, genital anomalies, severe developmental delay | Cholesterol metabolism |
| Neonatal lethal form of CPT II deficiency | CPT II | Grossly enlarged cystic kidneys | Microvesicular steatosis, hepatomegaly | Hypoketotic hypoglycaemia, cardiomyopathy | Mitochondrial fatty acid oxidation (CPTII is involved in carnitine cycle, which is required for long chain fatty acid transport into the mitochondria) |
| Glutaric acidaemia type II, severe variant with neonatal onset with congenital anomalies | ETF or ETF-QO | Grossly enlarged kidneys, cortical or medullary cysts, occasionally with dysplastic changes | Bile duct hypoplasia and cholestasis, microvesicular steatosis, hepatomegaly; in later onset may present with Reye’s syndrome | Facial dysmorphism, “rocker bottom” feet, CNS anomalies (neuronal migration defects), abdominal wall muscle defects, hyperammonaemia, cardiomyopathy | Intermediary electron carriers between primary flavoprotein dehydrogenases and terminal mitochondrial respiratory chains |
| Peroxisome biogenesis disorders: (a) Zellweger spectrum disorders (80%); includes ZS, NALD, IRD, HPA (b) RCDP (20%) | (a) Mutations in any of the PEX genes (b) Usually PEX7 mutations | Various renal cysts, including multiple microcysts (not reported in NALD and IRD) | Abnormalities in liver architecture, cholestasis, siderosis, fibrosis progressing to cirrhosis (not reported in RCDP) | Craniofacial dysmorphism, ocular abnormalities, CNS abnormalities, developmental delay, hypotonia and seizures, skeletal abnormalities (predominantly RCDP) | (a) Defect in function of all peroxisomal enzymes (b) Peroxisomal plasmalogen biosynthesis and branch chain fatty acid oxidation defects |
| Congenital disorder of glycosylation type Ia | PMM2 | Variable renal cysts, proteinuria | Steatosis, fibrosis, glycogen accumulation, occasionally liver failure | CNS abnormalities, hypogonadism, facial dysmorphic features, abnormal subcutaneous adipose tissue distribution, stroke-like episodes | Abnormal glycosylation of a large number of glycoproteins |